THE ROLE OF LGR5+ EPITHELIAL STEM-LIKE CELLS IN 3D-ORGANOID MODELING AND PATHOGENESIS OF AMELOBLASTOMA

Ameloblastoma (AM) is a benign yet locally aggressive tumor with high recurrences. Currently, the underlying pathophysiology remains elusive and radical surgery remains the most definitive treatment with severe morbidities. Our group first reported that AM harbors a subpopulation of tumor epithelial stem-like cells (AM-EpiSCs). Herein, this study further explored whether LGR5+ epithelial cells in AM possess unique stem-like cell properties and their potential contribution to the pathogenesis and recurrence of AM. Our findings demonstrated that LGR5 and stem cell-related genes were simultaneously expressed in a subpopulation of AM epithelial cells, both in vivo and in vitro, which were markedly enriched under the 3D-spheroid culture condition. As compared to LGR5- counterparts, LGR5+ AM epithelial cells showed increased expression of several critical genes involved in the regulation of epithelial-mesenchymal transition (EMT) and stem cell pluripotency, and functionally, exhibited enhanced capacity to form 3D-spheroids and generate human tumor 3D-organoids, which recapitulated characteristic histopathologic features of distinct subtypes of solid AM. Interestingly, AM derived mesenchymal stromal cells (AM-MSCs) and their secretomes or extracellular vesicles (EVs) significantly promoted the generation of LGR5+ AM-EpiSCs both in vitro and in vivo. Furthermore, treatment with a selective BRAFV600E inhibitor, Vemurafenib, unexpectedly enriched the proportion of LGR5+ AM-EpiSCs in AM 3D-organoids, which may explain the therapeutic resistant and recurrent properties of AM conferred by this unique subpopulation of AM-EpiSCs. Therefore, the tumor 3D-organoids generated by LGR5+ AM-EpiSCs provided a novel ex vivo platform for mechanistic studies of human AM and high throughput screening of targeted therapeutic drugs. These findings suggest that LGR5+ AM-EpiSCs play a pivotal role in pathogenesis and progression of AM and targeted inhibition of both BRAF and LGR5 potentially serves a novel non-surgical adjuvant therapeutic approach for this benign yet aggressively destructive jaw tumor

Systemic lupus erythematosus with initial presentation of empyematous pleural effusion in an elderly male patient: A diagnostic challenge

Systemic lupus erythematosus (SLE) poses great difficulty in making an early diagnosis in elderly males, often presenting with atypical manifestations. Acute onset of empyematous pleural effusion has rarely been seen. Herein, we report a 66-year-old man with SLE presenting with rapid progression of bilateral pleural effusion. Diagnostic thoracocentesis disclosed neutrophil-predominant exudates and chest computed tomography revealed multiple loculated pleural effusions. Nevertheless, optimal antibiotic therapy plus surgical decortication of the pleura did not improve his condition. The diagnosis of SLE was readily established after LE cells were accidentally found in the pleural effusion. Large amounts of pleural effusion subsided soon after high dose corticosteroid therapy

Loss of vesicular dopamine release precedes tauopathy in degenerative dopaminergic neurons in a Drosophila model expressing human tau.

While a number of genome-wide association studies have identified microtubule-associated protein tau as a strong risk factor for Parkinson's disease (PD), little is known about the mechanism through which human tau can predispose an individual to this disease. Here, we demonstrate that expression of human wild-type tau is sufficient to disrupt the survival of dopaminergic neurons in a Drosophila model. Tau triggers a synaptic pathology visualized by vesicular monoamine transporter-pHGFP that precedes both the age-dependent formation of tau-containing neurofibrillary tangle-like pathology and the progressive loss of DA neurons, thereby recapitulating the pathological hallmarks of PD. Flies overexpressing tau also exhibit progressive impairments of both motor and learning behaviors. Surprisingly, contrary to common belief that hyperphosphorylated tau could aggravate toxicity, DA neuron degeneration is alleviated by expressing the modified, hyperphosphorylated tau(E14). Together, these results show that impairment of VMAT-containing synaptic vesicle, released to synapses before overt tauopathy may be the underlying mechanism of tau-associated PD and suggest that correction or prevention of this deficit may be appropriate targets for early therapeutic intervention

(Re)negotiating and (Re)envisioning Our Feminist Journeys: A Collaborative Autoethnography of Five Women of Color Doctoral Students

This study utilizes critical collaborative autoethnography to explore the development, identity, and experiences as a feminist from five Women of Color doctoral students. Given that existing research on the experiences of doctoral women of color remains sparse, the purpose of this study is to expand the knowledge by highlighting and validating the lived experiences of doctoral women of color in the academy from a feminist perspective. Through the use of collaborative autoethnography, the authors explore and interrogate their individual journeys as self-identified or aspiring feminists. The findings present the living reality and complexity involving history, contexts, intersection of identities, conflicts, inter-/intra-racial coalition, and activism through these Women of Color doctoral students

Tailoring excitonic states of van der Waals bilayers through stacking configuration, band alignment and valley-spin

Excitons in monolayer semiconductors have large optical transition dipole for strong coupling with light field. Interlayer excitons in heterobilayers, with layer separation of electron and hole components, feature large electric dipole that enables strong coupling with electric field and exciton-exciton interaction, at the cost that the optical dipole is substantially quenched (by several orders of magnitude). In this letter, we demonstrate the ability to create a new class of excitons in transition metal dichalcogenide (TMD) hetero- and homo-bilayers that combines the advantages of monolayer- and interlayer-excitons, i.e. featuring both large optical dipole and large electric dipole. These excitons consist of an electron that is well confined in an individual layer, and a hole that is well extended in both layers, realized here through the carrier-species specific layer-hybridization controlled through the interplay of rotational, translational, band offset, and valley-spin degrees of freedom. We observe different species of such layer-hybridized valley excitons in different heterobilayer and homobilayer systems, which can be utilized for realizing strongly interacting excitonic/polaritonic gases, as well as optical quantum coherent controls of bidirectional interlayer carrier transfer either with upper conversion or down conversion in energy

p-Cu2O-shell/n-TiO2-nanowire-core heterostucture photodiodes

This study reports the deposition of cuprous oxide [Cu2O] onto titanium dioxide [TiO2] nanowires [NWs] prepared on TiO2/glass templates. The average length and average diameter of these thermally oxidized and evaporated TiO2 NWs are 0.1 to 0.4 μm and 30 to 100 nm, respectively. The deposited Cu2O fills gaps between the TiO2 NWs with good step coverage to form nanoshells surrounding the TiO2 cores. The p-Cu2O/n-TiO2 NW heterostructure exhibits a rectifying behavior with a sharp turn-on at approximately 0.9 V. Furthermore, the fabricated p-Cu2O-shell/n-TiO2-nanowire-core photodiodes exhibit reasonably large photocurrent-to-dark-current contrast ratios and fast responses

Studies on the protective effect of total flavonoids from Cichorium glandulosum roots against carbon tetrachloride-induced liver fibrosis in rats

Purpose: To study the protective influence of total flavonoids from Cichorium glandulosum roots (TFCG) against carbon tetrachloride-mediated hepatic fibrosis in rats, and the probable mechanism of action involved.Methods: Rats with liver fibrosis were orally administered TFCG (50, 100 or 200 mg/kg) once a day for 13 weeks. Liver index and liver injury indices in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), lactate dehydrogenase (LDH), γ-glutamyl transpeptidase (γ-GT), hydroxyproline (HYP), albumin (ALB) and malondialdehyde (MDA) were determined using electronic balance or corresponding assay kits, as appropriate. Following staining with hematoxylin and eosin and Van Gieson, histopathological changes in liver tissues were examined by light microscopy. TGF-β/Smad pathway-related protein expressions in liver tissues, viz, transforming growth factor-β1 (TGF-β1), mothers against decapentaplegic homolog 3 (Smad3), Smad7, toll-like receptor 4 (TLR4) and α-smooth muscle actin (α-SMA) were determined using immunohistochemical techniques.Results: Exposure to TFCG significantly reversed abnormal serum levels of ALT, AST, AKP, LDH, γ- GT, HYP, ALB and MDA rats with liver fibrosis to normal levels, and also decreased their liver index values (p < 0.01). Moreover, TFCG improved histopathological changes in the liver tissues of fibrotic rats, and significantly reversed abnormal TGF-β1, Smad3, Smad7, TLR4 and α-SMA protein expressions in the liver tissues of fibrotic rats to normal levels (p < 0.05 or 0.01).Conclusion: These results indicate that TFCG exerts protective effect against liver fibrosis via a mechanism related to inactivation of TGF-β/Smad pathway. Thus, TFCG may find application in liver fibrosis therapy.Keywords: Cichorium glandulosum, Flavonoids, Liver, Fibrosis, TGF-β/Smad pathwa