PTEN-regulated alternative splicing of FoxM1 affects tumor cell migration

Objective·To study the effect of phosphatase and tensin homolog on chromosome 10 (PTEN) on alternative splicing of forkhead box M1 (FoxM1), and its impact on tumor cell migration.Methods·PTEN was knocked down by short hairpin RNA (shRNA) in human embryonic kidney 293T cells, human prostate cancer DU145 cells, human colorectal adenocarcinoma RKO cells, and human colon cancer SW480 and SW620 cells. Specific primers were designed for FoxM1 and its subtypes FoxM1B and FoxM1C, and the mRNA expression levels of FoxM1B and FoxM1C were detected by quantitative real-time PCR (qRT-PCR). FoxM1B and FoxM1C were overexpressed in DU145 cells, and their effects on tumor cell migration were tested by Transwell assay and wound healing assay. Immunofluorescence and dual luciferase reporter gene assay were used to explore the potential mechanism of differential regulation of tumor cell migration by FoxM1B and FoxM1C.Results·① PTEN was knocked down in 293T, DU145, RKO, SW480, and SW620 cell lines. qRT-PCR results showed that compared with the control cells, the mRNA expression level of FoxM1B significantly increased in PTEN knockdown cells, while the mRNA expression level of FoxM1C decreased or remained unchanged. Knockdown of PTEN did not affect the transcription level of FoxM1, but caused the variable splicing of FoxM1 and promoted the generation of FoxM1B. ② Compared with the control cells, the number of DU145 cells migrating to the below chamber increased in the FoxM1B overexpression group (P=0.024), while the number of migrating DU145 cells in the FoxM1C overexpression group was lower (P=0.000). The healing ability of DU145 cells was significantly enhanced in the FoxM1B overexpression group (P=0.001), while the healing ability of DU145 cells was weakened in the FoxM1C overexpression group (P=0.021). Overall, FoxM1B and FoxM1C had opposite effects on tumor cell migration. FoxM1B promoted tumor cell migration, while FoxM1C inhibited tumor cell migration. ③ Neither FoxM1B nor FoxM1C overexpression could induce β-catenin to enter the nucleus. Dual luciferase reporter gene assay showed no difference in the transcriptional activity of FoxM1B and FoxM1C. The difference between FoxM1B and FoxM1C in the regulation of tumor metastasis was also not mediated by β-catenin translocation.Conclusion·Knockdown of PTEN regulates the alternative splicing of FoxM1, leading to increasing expression of transcript FoxM1B, which plays a positive role in tumor cell migration

High Ozone (O3) Affects the Fitness Associated with the Microbial Composition and Abundance of Q Biotype Bemisia tabaci

Abstract Ozone (O3) affects the fitness of an insect, such as its development, reproduction and protection against fungal pathogens, but the mechanism by which it does so remains unclear. Here, we compared the fitness (i.e., the growth and development time, reproduction and protection against Beauveria bassiana (B. bassiana) of Q biotype whiteflies fumigated under hO3 (280 ± 20 ppb) and control O3 (50 ± 10 ppb) concentrations. Moreover, we determined that gene expression was related to development, reproduction and immunity to B. bassiana and examined the abundance and composition of bacteria and fungi inside of the body and on the surface of the Q biotype whitefly. We observed a significantly enhanced number of eggs that were laid by a female, shortened developmental time, prolonged adult lifespan, decreased weight of one eclosion, and reduced immunity to B. bassiana in whiteflies under hO3, but hO3 did not significantly affect the expression of genes related to development, reproduction and immunity. However, hO3 obviously changed the composition of the bacterial communities inside of the body and on the surface of the whiteflies, significantly reducing Rickettsia and enhancing Candidatus_Cardinium. Similarly, hO3 significantly enhanced Thysanophora penicillioides from the Trichocomaceae family and reduced Dothideomycetes (at the class level) inside of the body. Furthermore, positive correlations were found between the abundance of Candidatus_Cardinium and the female whitefly ratio and the fecundity of a single female, and positive correlations were found between the abundance of Rickettsia and the weight of adult whiteflies just after eclosion and immunity to B. bassiana. We conclude that hO3 enhances whitefly development and reproduction but impairs immunity to B. bassiana, and our results also suggest that the changes to the microbial environments inside of the body and on the surface could be crucial factors that alter whitefly fitness under hO3. Key words: Bemisia tabaci, high ozone (hO3), fitness, microbial communities, inside of the body, on the surfac

Nursing students’ perceptions of their verbal and social interaction skills in Sweden and China during their first semester

Aim: This study aimed to investigate the similarities and differences related to verbal and social interaction skills between nursing students attending universities in Sweden and China, two countries with different educational systems, during the students’ first semester. Background: Nurses need a high level of interaction skills in order to interact effectively with patients and their families. Thus, practical nursing education focusing on clinical skills is essential. Method: Students at one university in Sweden and two universities in China completed the Verbal and Social Interactions for Nursing Students (VSI-NS) questionnaire. Results: The students perceived ‘Building a caring relationship’ and ‘Caring towards health and well-being’ as the most frequently occurring and important types of caring interactions. The students perceived that talking with a patient about his/her feelings and thoughts was the least frequently occurring and least important type of caring interaction. Conclusion: The students appear to understand from the initial phase of their education that the caring relationship and the patients’ health and well-being will be the major focus of their role as nurses. Résumé But : Cette étude visait à étudier les similitudes et les différences liées aux habiletés d’interaction verbale et sociale entre des étudiantes en sciences infirmières d’universités en Suède et en Chine, deux pays avec des systèmes d’enseignement différents, au cours du premier semestre des étudiantes. Contexte : Les infirmières ont besoin d’un niveau élevé d’habiletés interactionnelles afin d’interagir avec les patients et leurs familles. Ainsi, il est essentiel qu’elles puissent bénéficier d’une formation en sciences infirmières axée sur les habiletés cliniques. Méthode : Des étudiantes d’une université en Suède et de deux universités en Chine ont rempli le questionnaire Verbal and Social Interactions for Nursing Students (Interactions verbales et sociales pour les étudiantes en sciences infirmières; VSI-NS). Résultats : Les étudiantes percevaient qu’« Établir une relation de caring » et « Se soucier de la santé et du bien-être » étaient les formes d’interactions caring les plus fréquentes et les plus importantes. Les étudiantes ont perçu que parler avec un patient de ses sentiments et de ses pensées était le type d’interaction de caring le moins fréquent et le moins important. Conclusion : Les étudiantes semblent comprendre dès le début de leur formation que la relation de caring ainsi que la santé et le bien-être des patients se trouveront au centre de leur rôle d’infirmière

Multiwavelength Analysis of a Nearby Heavily Obscured AGN in NGC 449

We presented the multiwavelength analysis of a heavily obscured active galactic nucleus (AGN) in NGC 449. We first constructed a broadband X-ray spectrum using the latest NuSTAR and XMM-Newton data. Its column density ($\simeq 10^{24} \rm{cm}^{-2}$) and photon index ($\Gamma\simeq 2.4$) were reliably obtained by analyzing the broadband X-ray spectrum. However, the scattering fraction and the intrinsic X-ray luminosity could not be well constrained. Combined with the information obtained from the mid-infrared (mid-IR) spectrum and spectral energy distribution (SED) fitting, we derived its intrinsic X-ray luminosity ($\simeq 8.54\times 10^{42} \ \rm{erg\ s}^{-1}$) and scattering fraction ($f_{\rm{scat}}\simeq 0.26\%$). In addition, we also derived the following results: (1). The mass accretion rate of central AGN is about $2.54 \times 10^{-2} \rm{M}_\odot\ \rm{yr}^{-1}$, and the Eddington ratio is $8.39\times 10^{-2}$; (2). The torus of this AGN has a high gas-to-dust ratio ($N_{\rm H}/A_{\rm V}=8.40\times 10^{22}\ \rm{cm}^{-2}\ \rm{mag}^{-1}$); (3). The host galaxy and the central AGN are both in the early stage of co-evolution.Comment: 12 pages, 5 figures, 3 tables, Accepted to PAS

PGC 38025: A Star-forming Lenticular Galaxy With an Off-nuclear Star-forming Core

Lenticular galaxies (S0s) were considered mainly as passive evolved spirals due to environmental effects for a long time; however, most S0s in the field cannot fit into this common scenario. In this work, we study one special case, SDSS J120237.07+642235.3 (PGC 38025), a star-forming field S0 galaxy with an off-nuclear blue core. We present optical integral field spectroscopic (IFS) observation with the 3.5 meter telescope at Calar Alto (CAHA) Observatory, and high-resolution millimeter observation with the NOrthern Extended Millimeter Array (NOEMA). We estimated the star formation rate (SFR = 0.446 $M_\odot yr^{-1}$) and gaseous metallicity (12 + log(O/H) = 8.42) for PGC 38025, which follows the star formation main sequence and stellar mass - metallicity relation. We found that the ionized gas and cold molecular gas in PGC 38025 show the same spatial distribution and kinematics, whilst rotating misaligned with stellar component. The off-nuclear blue core is locating at the same redshift as PGC 38025 and its optical spectrum suggest it is \rm H\,{\sc ii} region. We suggest that the star formation in PGC 38025 is triggered by a gas-rich minor merger, and the off-nuclear blue core might be a local star-formation happened during the accretion/merger process.Comment: 16 pages, 13 figures, accepted for publication in Ap

Host galaxy properties of changing-look AGNs revealed in the MaNGA survey

Changing-look active galactic nuclei (CL-AGNs) are a subset of AGNs in which the broad Balmer emission lines appear or disappear within a few years. We use the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey to identify five CL-AGNs. The 2D photometric and kinematic maps reveal common features as well as some unusual properties of CL-AGN hosts as compared to the AGN hosts in general. All MaNGA CL-AGNs reside in the star-forming main sequence, similar to MaNGA non-changing-look AGNs (NCL-AGNs). The 80 ± 16 per cent of our CL-AGNs do possess pseudo-bulge features, and follow the overall NCL-AGN MBH–σ∗ relationship. The kinematic measurements indicate that they have similar distributions in the plane of angular momentum versus galaxy ellipticity. MaNGA CL-AGNs, however, show a higher, but not statistically significant (20 ± 16 per cent) fraction of counter-rotating features compared to that (1.84 ± 0.61 per cent) in general star formation population. In addition, MaNGA CL-AGNs favour more face-on (axial ratio > 0.7) than that of type I NCL-AGNs. These results suggest that host galaxies could play a role in the CL-AGN phenomenon

Analysis of Insulin Doses of Chinese Type 2 Diabetic Patients with Intensive Insulin Treatment

BACKGROUND: To investigate the daily insulin doses and the ratio of basal insulin to total daily insulin in Chinese type 2 diabetic patients who received basal bolus insulin therapy. METHODOLOGY/PRINCIPAL FINDINGS: Totally 2480 patients prescribed with pre-meal bolus insulin and bedtime basal insulin were included. The mean daily insulin doses was 38.22 ± 14.92 IU/day, the mean daily insulin doses per weight was 0.58 ± 0.22 IU/kg, the mean bolus insulin dose was 0.44 ± 0.17 IU/kg and the mean basal insulin dose was 0.13 ± 0.08 IU/kg. The mean basal/total daily insulin ratio (BD/TDD) was 0.23 ± 0.08. In most patients (47.94%), the BD/TDD was between 0.20 and 0.30. Diabetic duration, BMI, HbA1c, fasting and postprandial blood glucose level were positively associated with daily insulin dose, while age was negatively associated with daily insulin dose. Diabetic duration, BMI, HbA1c, fasting blood glucose level, and using metformin were positively associated with BD/TDD ratio, while age, postprandial C peptide, postprandial blood glucose level and CRE level were negatively associated with BD/TDD ratio. CONCLUSIONS/SIGNIFICANCE: The daily insulin doses of intensive treatment in Chinese type 2 diabetic patients was 38.22 IU/day, the mean daily insulin doses per weight was 0.58 IU/kg, mean BD/TDD ratio was 0.23

Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape

Tumor immune escape is an important strategy of tumor survival. There are many mechanisms of tumor immune escape, including immunosuppression, which has become a research hotspot in recent years. The programmed death ligand-1/programmed death-1 (PD-L1/PD-1) signaling pathway is an important component of tumor immunosuppression, which can inhibit the activation of T lymphocytes and enhance the immune tolerance of tumor cells, thereby achieving tumor immune escape. Therefore, targeting the PD-L1/PD-1 pathway is an attractive strategy for cancer treatment; however, the therapeutic effectiveness of PD-L1/PD-1 remains poor. This situation requires gaining a deeper understanding of the complex and varied molecular mechanisms and factors driving the expression and activation of the PD-L1/PD-1 signaling pathway. In this review, we summarize the regulation mechanisms of the PD-L1/PD-1 signaling pathway in the tumor microenvironment and their roles in mediating tumor escape. Overall, the evidence accumulated to date suggests that induction of PD-L1 by inflammatory factors in the tumor microenvironment may be one of the most important factors affecting the therapeutic efficiency of PD-L1/PD-1 blocking