Id2 promotes the invasive growth of MCF-7 and SKOV-3 cells by a novel mechanism independent of dimerization to basic helix-loop-helix factors

<p>Abstract</p> <p>Background</p> <p>Inhibitor of differentiation 2 (<it>Id2</it>) is a critical factor for cell proliferation and differentiation in normal vertebrate development. Most of the biological function of Id2 has been ascribed to its helix-loop-helix motif. Overexpression of Id2 is frequently observed in various human tumors, but its role for invasion potential in tumor cells is dispute. We aimed to reveal the role of Id2 in invasion potential in poorly invasive and estrogen receptor α (ERα)-positive MCF-7 and SKOV-3 cancer cells.</p> <p>Methods</p> <p>MCF-7 and SKOV-3 cells were stably transfected with the wild-type, degradation-resistant full-length or helix-loop-helix (HLH)-deleted Id2, respectively. Protein levels of Id2 and its mutants and E-cadherin were determined by western blot analysis and mRNA levels of Id2 and its mutants were determined by RT-PCR. The effects of Id2 and its mutants on cell proliferation were determined by [³H]-thymidine incorporation assay and the 3- [4, 5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) dye method. The <it>in vitro </it>invasion potential of cells was evaluated by Transwell assay. Cell motility was assessed by scratch wound assay. The promoter activity of <it>E-cadherin </it>was determined by cotransfection and luciferase assays.</p> <p>Results</p> <p>Ectopic transfection of the wild-type Id2 markedly increased the protein and mRNA expression of <it>Id2 </it>in MCF-7 and SKOV-3 cells; the protein level but not mRNA level was further increased by transfection with the degradation-resistant Id2 form. The ectopic expression of Id2 or its mutants did not alter proliferation of either MCF-7 or SKOV-3 cells. Transfection of the wild-type Id2 significantly induced the invasion potential and migratory capacity of cells, which was further augmented by transfection with the degradation-resistant full-length or HLH-deleted Id2. E-cadherin protein expression and transactivation of the proximal E-cadherin promoter were markedly suppressed by the degradation-resistant full-length or HLH-deleted Id2 but not wild-type Id2. Ectopic expression of E-cadherin in MCF-7 and SKOV-3 cells only partially blunted the invasion potential induced by the degradation-resistant HLH-deleted Id2.</p> <p>Conclusion</p> <p>Overexpression of Id2 in ERα-positive epithelial tumor cells indeed increases the cells' invasive potential through a novel mechanism independent of dimerization to basic helix-loop-helix factors. E-cadherin contributes only in part to Id2-induced cell invasion when Id2 is accumulated to a higher level in some specific cell types.</p

Efficacy of a smartphone-based care support programme in improving post-traumatic stress in families with childhood cancer: Protocol of a randomised controlled trial

INTRODUCTION: Diagnosis and treatment represent distressing experiences for the families of children with cancer. Psychosocial challenges are faced by these families in China because of limited health services and resources for psychosocial oncology care. Effective interventions tailored to the knowledge level and cultural values of this population are needed. The goal of this study is to evaluate a smartphone-based care support (SBCS) programme for the families of children with cancer in China. METHODS AND ANALYSIS: A parallel randomised controlled trial will be conducted to examine the efficacy of an evidence-based and culturally tailored SBCS programme for the families of children with cancer in China. A total of 180 families will be recruited. The intervention will consist of an introduction session and four main sessions and will be conducted sequentially on a single weekend day. Participating families will be included in the intervention group. The post-traumatic stress and quality of life of families will be evaluated at baseline, during the intervention, immediately after the intervention, and 2 and 6 months after the intervention. ETHICS AND DISSEMINATION: Ethical approval for this protocol has been obtained from the Nursing and Behavioural Medicine Research Ethics Review Committee, Xiangya School of Nursing, Central South University (Protocol #: E2020125). The findings of the trial will be disseminated through conference presentations and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2000040510

Gain-gain and gain-lossless PT-symmetry broken from PT-phase diagram

Parity-time (PT) symmetry and broken in micro/nano photonic structures have been investigated extensively as they bring new opportunities to control the flow of light based on non-Hermitian optics. Previous studies have focused on the situations of PT-symmetry broken in loss-loss or gain-loss coupling systems. Here, we theoretically predict the gain-gain and gain-lossless PT-broken from phase diagram, where the boundaries between PT-symmetry and PT-broken can be clearly defined in the full-parameter space including gain, lossless and loss. For specific micro/nano photonic structures, such as coupled waveguides, we give the transmission matrices of each phase space, which can be used for beam splitting. Taking coupled waveguides as an example, we obtain periodic energy exchange in PT-symmetry phase and exponential gain or loss in PT-broken phase, which are consistent with the phase diagram. The scenario giving a full view of PT-symmetry or broken, will not only deepen the understanding of fundamental physics, but also will promote the breakthrough of photonic applications like optical routers and beam splitters

Differential analysis of serum immunology and gut microbiota in patients with gastrointestinal diseases

ObjectiveGastric and intestinal diseases possess distinct characteristics although they are interconnected. The primary objective of this study was to investigate the pathogenesis of gastrointestinal diseases through different analyses of clinical characteristics, serum immunology, and gut microbiota in patients with gastrointestinal diseases.MethodsWe collected serum samples from 89 patients with gastrointestinal diseases and 9 healthy controls for immunological assessment, stool samples for DNA extraction, library construction, sequencing, as well as clinical data for subsequent analysis.ResultsRegarding clinical characteristics, there were significant differences between the disease group and the healthy control (HC) group, particularly in terms of age, cancer antigen 125 (CA125), cancer antigen 199 (CA199), alpha-fetoprotein (AFP), total bilirubin (TBIL) and indirect bilirubin (IBIL). The intestinal disease (ID) group exhibited the highest IL-6 level, which significantly differed from the stomach disease (SD) group (p &lt; 0.05). In comparing the HC with the ID groups, significant differences in abundance were detected across 46 species. The HC group displayed a greater abundance of Clostridiales, Clostridia, Firmicutes, Bifidobacterium, Bifidobacteriaceae, Bifidobacteriales, Actinobacteria, Veillonellaceae, Longum, Copri, Megamonas and Callidus than other species. Similarly, when comparing the HC with the SD groups, significant differences in abundance were identified among 49 species, with only one species that the Lachnospiraceae in the HC group exhibited a higher abundance than others. Furthermore, certain clinical characteristics, such as CA125, CA199, glucose (Glu), creatine kinase-MB (CKMB) and interleukin-22 (IL-22), displayed positive correlations with enriched gut species in the ID and SD groups, while exhibiting a negative correlation with the HC group.ConclusionThe disturbance in human gut microbiota is intimately associated with the development and progression of gastrointestinal diseases. Moreover, the gut microbiota in the HC group was found more diverse than that in the ID and SD groups, and there were significant differences in microbial species among the three groups at different classification levels. Notably, a correlation was identified between specific clinical characteristics (e.g., CA125, CA199, Glu, CKMB and IL-22) and gut microbiota among patients with gastrointestinal diseases

Quantum PT-Phase Diagram in a Non-Hermitian Photonic Structure

Photonic structures have an inherent advantage to realize PT-phase transition through modulating the refractive index or gain-loss. However, quantum PT properties of these photonic systems have not been comprehensively studied yet. Here, in a bi-photonic structure with loss and gain simultaneously existing, we analytically obtained the quantum PT-phase diagram under the steady state condition. To characterize the PT-symmetry or -broken phase, we define an Hermitian exchange operator expressing the exchange between quadrature variables of two modes. If inputting several-photon Fock states into a PT-broken bi-waveguide splitting system, most photons will concentrate in the dominant waveguide with some state distributions. Quantum PT-phase diagram paves the way to the quantum state engineering, quantum interferences, and logic operations in non-Hermitian photonic systems.Comment: 6 pages, 3 figure

Detection and attribution of nitrogen runoff trend in China's croplands

Reliable detection and attribution of changes in nitrogen (N) runoff from croplands are essential for designing efficient, sustainable N management strategies for future. Despite the recognition that excess N runoff poses a risk of aquatic eutrophication, large-scale, spatially detailed N runoff trends and their drivers remain poorly understood in China. Based on data comprising 535 site-years from 100 sites across China's croplands, we developed a data-driven upscaling model and a new simplified attribution approach to detect and attribute N runoff trends during the period of 1990–2012. Our results show that N runoff has increased by 46% for rice paddy fields and 31% for upland areas since 1990. However, we acknowledge that the upscaling model is subject to large uncertainties (20% and 40% as coefficient of variation of N runoff, respectively). At national scale, increased fertilizer application was identified as the most likely driver of the N runoff trend, while decreased irrigation levels offset to some extent the impact of fertilization increases. In southern China, the increasing trend of upland N runoff can be attributed to the growth in N runoff rates. Our results suggested that increased SOM led to the N runoff rate growth for uplands, but led to a decline for rice paddy fields. In combination, these results imply that improving management approaches for both N fertilizer use and irrigation is urgently required for mitigating agricultural N runoff in China

Pathogenic Role of mTORC1 and mTORC2 in Pulmonary Hypertension.

Concentric lung vascular wall thickening due to enhanced proliferation of pulmonary arterial smooth muscle cells is an important pathological cause for the elevated pulmonary vascular resistance reported in patients with pulmonary arterial hypertension. We identified a differential role of mammalian target of rapamycin (mTOR) complex 1 and complex 2, two functionally distinct mTOR complexes, in the development of pulmonary hypertension (PH). Inhibition of mTOR complex 1 attenuated the development of PH; however, inhibition of mTOR complex 2 caused spontaneous PH, potentially due to up-regulation of platelet-derived growth factor receptors in pulmonary arterial smooth muscle cells, and compromised the therapeutic effect of the mTOR inhibitors on PH. In addition, we describe a promising therapeutic strategy using combination treatment with the mTOR inhibitors and the platelet-derived growth factor receptor inhibitors on PH and right ventricular hypertrophy. The data from this study provide an important mechanism-based perspective for developing novel therapies for patients with pulmonary arterial hypertension and right heart failure

Prognostic and therapeutic significance of microbial cell-free DNA in plasma of people with acutely decompensated cirrhosis

BACKGROUND AND AIMS: Although the effect of bacterial infection on cirrhosis has been well-described, the effect of non-hepatotropic virus (NHV) infection is unknown. This study evaluated the genome fragments of circulating microorganisms using metagenomic next-generation sequencing (mNGS) in cirrhosis patients with acute decompensation (AD), focusing on NHVs and related the findings to clinical outcomes. METHODS: Plasma mNGS was performed in 129 cirrhosis patients with AD in study cohort. Ten healthy volunteers and 20, 39, and 81 patients with stable cirrhosis, severe sepsis and hematological malignancies, respectively, were enrolled as controls. Validation assays for human cytomegalovirus (CMV) reactivation in a validation cohort (n = 58) were performed and exploratory treatment instituted. RESULTS: In study cohort, 188 microorganisms were detected in 74.4% (96/129) patients, including viruses (58.0%), bacteria (34.1%), fungi (7.4%) and chlamydia (0.5%). Patients with AD had an NHV signature, and CMV was the most frequent NHV, which correlated with the clinical effect of empirical antibiotic treatment, progression to acute-on-chronic liver failure (ACLF), and 90-day mortality. The NHV signature in ACLF patients was similar to patients with sepsis and hematological malignancies. The treatable NHV, CMV was detected in 24.1% (14/58) patients in the validation cohort. Of the 14 cases with detectable CMV by mNGS, 9 were further validated by DNA RT-PCR or pp65 antigenemia testing. Three patients with CMV reactivation received ganciclovir therapy in exploratory manner with clinical resolutions. CONCLUSIONS: The results of this study suggests that NHVs may have a pathogenic role in complicating the course of AD. Further validation is needed to define whether this should be incorporated in the routine management of AD patients. IMPACT AND IMPLICATIONS: ●Cirrhosis patients with acute decompensation have a non-hepatotropic virus (NHV) signature, which is similar to that in sepsis and hematological malignancies patients. ●The detected viral signature had clinical correlates, including clinical efficacy of empirical antibiotic treatment, progression to acute-on-chronic liver failure and short-term mortality. ●The treatable NHV, CMV reactivation may be involved in the clinical outcomes of decompensated cirrhosis. ●Routine screening for NHVs, especially CMV, may be useful for the management of patients with acutely decompensated cirrhosis