EGFR signaling controls directionality of epithelial multilayer formation upon loss of cell polarity.

Apical-basal polarity is maintained by distinct protein complexes that reside in membrane junctions, and polarity loss in monolayered epithelial cells can lead to formation of multilayers, cell extrusion, and/or malignant overgrowth. Yet, how polarity loss cooperates with intrinsic signals to control directional invasion toward neighboring epithelial cells remains elusive. Using the Drosophila ovarian follicular epithelium as a model, we found that posterior follicle cells with loss of lethal giant larvae (lgl) or Discs large (Dlg) accumulate apically toward germline cells, whereas cells with loss of Bazooka (Baz) or atypical protein kinase C (aPKC) expand toward the basal side of wildtype neighbors.

Cell polarity opposes Jak/STAT-mediated Escargot activation that drives intratumor heterogeneity in a Drosophila tumor model.

In proliferating neoplasms, microenvironment-derived selective pressures promote tumor heterogeneity by imparting diverse capacities for growth, differentiation, and invasion. However, what makes a tumor cell respond to signaling cues differently from a normal cell is not well understood. In the Drosophila ovarian follicle cells, apicobasal-polarity loss induces heterogeneous epithelial multilayering.

Single-cell transcriptomics identifies Keap1-Nrf2 regulated collective invasion in a tumor model.

Apicobasal cell polarity loss is a founding event in epithelial-mesenchymal transition and epithelial tumorigenesis, yet how pathological polarity loss links to plasticity remains largely unknown. To understand the mechanisms and mediators regulating plasticity upon polarity loss, we performed single-cell RNA sequencing of ovaries, where inducing polarity-gene -knockdown (Lgl-KD) causes invasive multilayering of the follicular epithelia. Analyzing the integrated Lgl-KD and transcriptomes, we discovered the cells specific to the various discernible phenotypes and characterized the underlying gene expression.

Modeling Notch-Induced Tumor Cell Survival in the Ovary Identifies Cellular and Transcriptional Response to Nuclear NICD Accumulation.

Notch is a conserved developmental signaling pathway that is dysregulated in many cancer types, most often through constitutive activation. Tumor cells with nuclear accumulation of the active Notch receptor, NICD, generally exhibit enhanced survival while patients experience poorer outcomes. To understand the impact of NICD accumulation during tumorigenesis, we developed a tumor model using the ovarian follicular epithelium.

Polyploidy in development and tumor models in Drosophila.

Polyploidy, a cell status defined as more than two sets of genomic DNA, is a conserved strategy across species that can increase cell size and biosynthetic production, but the functional aspects of polyploidy are nuanced and vary across cell types. Throughout Drosophila developmental stages (embryo, larva, pupa and adult), polyploid cells are present in numerous organs and help orchestrate development while contributing to normal growth, well-being and homeostasis of the organism. Conversely, increasing evidence has shown that polyploid cells are prevalent in Drosophila tumors and play important roles in tumor growth and invasiveness.

Polyploid mitosis and depolyploidization promote chromosomal instability and tumor progression in a Notch-induced tumor model.

Ploidy variation is a cancer hallmark and is frequently associated with poor prognosis in high-grade cancers. Using a Drosophila solid-tumor model where oncogenic Notch drives tumorigenesis in a transition-zone microenvironment in the salivary gland imaginal ring, we find that the tumor-initiating cells normally undergo endoreplication to become polyploid. Upregulation of Notch signaling, however, induces these polyploid transition-zone cells to re-enter mitosis and undergo tumorigenesis.

External electric field reduces the explosive sensitivity: a theoretical investigation into the hydrogen transference kinetics of the NHNO∙∙∙HO complex.

Controlling the selectivity of detonation initiation reaction to reduce the explosive sensitivity has been a Holy Grail in the field of energetic materials. The effects of the external electric fields on the homolysis of the N-NO bond and initiation reaction dynamics of NHNO∙∙∙HO (i.e.

The clinical efficacy and adverse effects of Entecavir plus Thymosin alpha-1 combination therapy versus Entecavir Monotherapy in HBV-related cirrhosis: a systematic review and meta-analysis.

Background: Previous studies have demonstrated the benefits of thymosin alpha-1 (Tα1) in anti-virus, immunological enhancement and anti-inflammation. However, it is controversial about the efficacy and safety of entecavir (ETV) plus Tα1 combination therapy versus ETV monotherapy in cirrhotic patients with hepatitis B virus (HBV) infection.

Methods: The systematic review and meta-analysis of randomized clinical trials (RCTs) were performed to evaluate the efficacy and safety of ETV plus Tα1 combination therapy versus ETV monotherapy in HBV-related patients with cirrhosis.

Evolutionarily Conserved Roles for Apontic in Induction and Subsequent Decline of Cyclin E Expression.

Cyclin E is a key factor for S phase entry, and deregulation of Cyclin E results in developmental defects and tumors. Therefore, proper cycling of Cyclin E is crucial for normal growth. Here we found that transcription factors Apontic (Apt) and E2f1 cooperate to induce cyclin E in Drosophila.

The Effects of Oral Polysaccharide Administration on Immune Responses, Antioxidant Activity and Resistance Against in the Common Carp, L.

The effects of the oral administration of polysaccharide (RGP-1) on the immunoregulatory properties, antioxidant activity, and resistance against in L. were investigated. The purified RGP-1 (250, 500, and 1,000 μg/mL) was co-cultured with the head kidney cells of the common carp.

[Asymptomatic SARS-CoV-2 infection in children: a clinical analysis of 20 cases].

Objective: To study the clinical and epidemiological features of children with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods: The clinical data of 20 children who were diagnosed with asymptomatic SARS-CoV-2 infection from January 20 to March 4, 2020 were analyzed.

Results: Among the 20 children, there were 7 boys (35%) and 13 girls (65%), aged 8 months to 14 years (mean 8±5 years).

A single-cell atlas of adult Drosophila ovary identifies transcriptional programs and somatic cell lineage regulating oogenesis.

Oogenesis is a complex developmental process that involves spatiotemporally regulated coordination between the germline and supporting, somatic cell populations. This process has been modeled extensively using the Drosophila ovary. Although different ovarian cell types have been identified through traditional means, the large-scale expression profiles underlying each cell type remain unknown.

Mbf1 ensures Polycomb silencing by protecting mRNA from degradation by Pacman.

Under stress conditions, the coactivator Multiprotein bridging factor 1 (Mbf1) translocates from the cytoplasm into the nucleus to induce stress-response genes. However, its role in the cytoplasm, where it is mainly located, has remained elusive. Here, we show that Mbf1 associates with mRNA and protects it from degradation by the exoribonuclease Pacman (Pcm), thereby ensuring Polycomb silencing.

Apontic directly activates hedgehog and cyclin E for proper organ growth and patterning.

Hedgehog (Hh) signaling pathway and Cyclin E are key players in cell proliferation and organ development. Hyperactivation of hh and cyclin E has been linked to several types of cancer. However, coordination of the expression of hh and cyclin E was not well understood.

A retrospective analysis of 56 children with hemophagocytic lymphohistiocytosis.

Aim: The aim of this study was to investigate the etiological factors, clinical features, and prognostic factors in children with hemophagocytic lymphohistiocytosis (HLH).

Methods: Fifty-six children with HLH in Wuhan Union Hospital, People's Republic of China, were retrospectively analyzed in recent years. We reviewed the medical records of 56 HLH children hospitalized from 2000 to 2013 to identify the possible prognostic factors.

Adiponectin treatment attenuates inflammatory response during early sepsis in obese mice.

Background: Morbid obesity increases the cost of care in critically ill patients. Sepsis is the leading cause of death in noncoronary intensive care units. Circulating cell-endothelial cell interactions in microcirculation are the rate-determining factors in any inflammation; obesity increases these interactions further.

The T-box transcription factor Midline regulates wing development by repressing wingless and hedgehog in Drosophila.

Wingless (Wg) and Hedgehog (Hh) signaling pathways are key players in animal development. However, regulation of the expression of wg and hh are not well understood. Here, we show that Midline (Mid), an evolutionarily conserved transcription factor, expresses in the wing disc of Drosophila and plays a vital role in wing development.

The Cytoprotective Effect of Hyperoside against Oxidative Stress Is Mediated by the Nrf2-ARE Signaling Pathway through GSK-3β Inactivation.

Glycogen synthase kinase-3β (GSK-3β) acts as a negative regulator of NF-E2 related factor 2 (Nrf2) by inducing Nrf2 degradation and nuclear export. Our previous study demonstrated that the flavonoid hyperoside elicits cytoprotection against oxidative stress by activating the Keap1-Nrf2-ARE signaling pathway, thus increasing the expression of antioxidant enzymes, such as heme oxygenase-1 (HO-1), superoxide dismutase (SOD) and catalase. However, the role of GSK-3β in hyperoside-mediated Nrf2 activation is unclear.

Evolutionarily conserved transcription factor Apontic controls the G1/S progression by inducing cyclin E during eye development.

During Drosophila eye development, differentiation initiates in the posterior region of the eye disk and progresses anteriorly as a wave marked by the morphogenetic furrow (MF), which demarcates the boundary between anterior undifferentiated cells and posterior differentiated photoreceptors. However, the mechanism underlying the regulation of gene expression immediately before the onset of differentiation remains unclear. Here, we show that Apontic (Apt), which is an evolutionarily conserved transcription factor, is expressed in the differentiating cells posterior to the MF.

Clinical and epidemiological analysis of the first case of human infection with avian influenza A (H7N9) virus in Shenzhen, China.

The novel influenza A (H7N9) virus can cause severe illness, including pneumonia and acute respiratory disorder syndrome (ARDS), with high rates of intensive care unit admission and death. We report the first case of human infection with avian influenza A (H7N9) virus in Shenzhen, China. The patient was a 38-year-old man.

Therapeutic effects of PADRE-BAFF autovaccine on rat adjuvant arthritis.

B cell activating factor (BAFF) is a cytokine of tumor necrosis factor family mainly produced by monocytes and dendritic cells. BAFF can regulate the proliferation, differentiation, and survival of B lymphocytes by binding with BAFF-R on B cell membrane. Accumulating evidences showed that BAFF played crucial roles and was overexpressed in various autoimmune diseases such as systemic lupus erythematous (SLE) and rheumatoid arthritis (RA).

The role of indoleamine 2,3-dioxygenase (IDO) in immune tolerance: focus on macrophage polarization of THP-1 cells.

Macrophages can be divided into two groups as M1 and M2 phenotype. Our results and other groups revealed that IFN-γ can up-regulate the IDO expression and differentiate THP-1 cells to M1 phenotype. Therefore we hypothesized that IDO may play potential roles in macrophage differentiation.