Excitonic Complexes and Optical Gain in Two-Dimensional Molybdenum Ditelluride Well below Mott Transition

Strong Coulomb interaction in 2D materials provides unprecedented opportunities for studying many key issues of condensed matter physics, such as co-existence and mutual conversions of excitonic complexes, fundamental optical processes associated with their conversions, and their roles in the celebrated Mott transition. Recent lasing demonstrations in 2D materials raise important questions about the existence and origin of optical gain and possible roles of excitonic complexes. While lasing occurred at extremely low densities dominated by various excitonic complexes, optical gain was observed in the only experiment at densities several orders of magnitude higher, exceeding the Mott density. Here, we report a new gain mechanism involving charged excitons or trions well below the Mott density in 2D molybdenum ditelluride. Our combined experimental and modeling study not only reveals the complex interplays of excitonic complexes well below the Mott transition, but also provides foundation for lasing at extremely low excitation levels, important for future energy efficient photonic devices

The protective effects of GM-0111 against LL-37 induced cystitis are more powerful than other GAG compounds.

<p>The animals receiving each compound at 10/mL dosage by intravesical instillation prior to LL-37 instillation showed variable responses in clinical signs of IC and decreased molecular markers in the serum and tissues. Only the animals treated with GM-0111 were effectively protected from the LL-37 challenge. *<i>p</i><0.05, **<i>p</i><0.01, and ***<i>p</i><0.001 compared to either normal or PBS/LL-37 instilled control group. NS, not significant (<i>p</i>>0.05) by Dunnet’s <i>t</i>-test. Black horizontal bars are mean or median (necropsy and histology scores) values. BDL and the values in the parenthesis represent the number of samples that fell below the detection limit (red dotted line) of the ELISA out of the total samples tested. For data analysis purposes, any values below the detection limit were listed as being at the detection limit, which may in some cases overestimate the numerical value. Gray area represents the range of values found in normal animals.</p

The protective effects of GM-0111 and heparin against LL-37 induced cystitis are more powerful than chondroitin sulfate or pentosan polysulfate.

<p>The animals receiving each compound at 100/mL dosage by intravesical instillation prior to LL-37 instillation showed markedly reduced clinical signs of IC and decreased molecular markers in the serum and tissues. *<i>p</i><0.05, **<i>p</i><0.01, and ***<i>p</i><0.001 compared to either normal or PBS/LL-37 instilled control group. NS, not significant (<i>p</i>>0.05) by Dunnet’s t-test. Black horizontal bars are the mean or median (necropsy and histology scores) values. BDL and the values in the parenthesis represent the number of samples that fell below the detection limit (red dotted line) of the ELISA out of the total samples tested. For data analysis purposes, any values below the detection limit were listed as being at the detection limit, which may in some cases overestimate the numerical value. Gray area represents the range of values found in normal animals.</p

Human umbilical cord-mesenchymal stem cells-derived exosomes carrying microRNA-15a-5p possess therapeutic effects on Wilms tumor via regulating septin 2

The exact mechanism of miR-15a-5p shuttled by human umbilical cord-mesenchymal stem cell-derived exosomes (hUC-MSCs-Exo) in Wilms tumor (WT) was estimated. WT tissues were collected clinically. miR-15a-5p and septin 2 (SEPT2) expression levels were examined in tissues . hUC-MSCs-Exo were transfected with miR-15a-5p-related oligonucleotides and co-cultured with WT cells (G-401). In addition, SEPT2 loss-of-function was performed in G-401 cells. The biological functions of G-401 cells after treatments were evaluated. Moreover, tumor formation tests further assessed the role of exosomal miR-15a-5p in WT. The miR-15a-5p level was lower and the SEPT2 level was higher in WT. hUC-MSCs-Exo impaired the biological functions of G-401 cells. hUC-MSCs-Exo carried upregulated miR-15a-5p into G-401 cells, thereby lessening the tumorigenic properties of G-401 cells. Inhibition of SEPT2 suppressed the biological function of WT cells and upregulated SEPT2 reversed hUC-MSCs-Exo-mediated inhibition of G-401 cell growth. The tumorigenicity of G-401 cells in mice was impaired by hUC-MSCs-Exo overexpressing miR-15a-5p. The data prove that miR-15a-5p shuttled by hUC-MSCs-Exo negatively regulates SEPT2 expression, and disrupts WT cell growth in vivo and in vitro.</p

Threshold-like Superlinear Accumulation of Excitons in a Gated Monolayer Transition Metal Dichalcogenide

Coexistence and mutual conversion of various excitonic species in semiconductors are the essence of Mott physics and underpin important device applications such as excitonic or polaritonic lasers. The emergence of monolayer semiconductors provides unprecedented opportunities to study these fundamental issues due to the much larger exciton binding energies. In this paper, we study the evolution of the coupled exciton–trion system in electrically gated monolayer MoTe2 devices. Contrary to the conventional linear scaling, we found that exciton density exhibits an abnormal three-stage scaling behavior: a conventional linear scaling at low pumping levels, followed by a superlinear behavior accompanied by a strong saturation of trion emission. In the third stage, the exciton emission returns to the linear scaling with the further increase of pumping. Although such behavior has a rare similarity in other physical systems, surprisingly we discovered a complete analogy of this behavior with the threshold of a conventional laser and proved mathematically that the exciton–trion equations are identical to the laser equations. We further showed that the power-law index increases with the charge density experimentally and can be as high as 40 at a density of ∼1 × 1012/cm2 in principle, leading to extremely nonlinear behavior of exciton accumulation. Our results reveal a new behavior of exciton accumulation and provide an alternative mechanism for multiplying exciton population, in analogy to a condensate. The intricate dynamics between excitons and trions will also enrich our understanding of the complex Mott physics in 2D semiconductors and may lead to new devices based on the exciton nonlinearity

GM-0111 reduces LL-37 induced apoptosis in human urothelial cells (HUCs).

<p>HUCs pretreated with GM-0111 at 0, 0.1, 1.0, and 10 mg/mL for 30 min were challenged with LL-37 (25 µM) for 15 min at 37°C. Cells were stained with annexin V-FITC (shown in green) and 7-AAD (shown in red) to visualize (A) with microscopy (magnification 10<i>x</i>) and to quantify (B) the apoptotic cells with flow cytometry. **<i>p</i><0.01, ***<i>p</i><0.001 and NS, not significant (<i>p</i>>0.05) by Dunnet’s <i>t</i>-test.</p

Multivariate analysis of various observations in LL-37 induced cystitis model and the inhibitory effects of GM-0111.

<p>Each intersecting graph shows the correlation between the two respective observational parameters. Graphs in the diagonal array represent the distribution of data from each parameter pooled from normal and LL-37/GM-0111 treated animals. Green lines indicate the correlation in each set of parameters and red dotted lines indicate the values following similar trends. Bold rectangular areas represent the correlation between physiological measurements and the concentrations of molecular markers. The values inside boxes are Spearman correlation coefficients (ρ).</p

LL-37 induces inflammatory changes in the urinary bladder (A, B, C, and D: normal bladder; E, F, G, and H: 24 hr after 250 µM LL-37 treatment).

<p>Microscopic observations show that LL-37 causes edema (*), massive infiltration of leukocytes including PMNs and occasional hemorrhage (black arrow head) along with urothelial erosion (arrow). A and E are photostiched images of the entire bladder surface stained with H&E (lower panels are the enlarged views of the square regions). B and F are immunostained images for Ly6G, the surface antigen from PMNs (blue arrowheads). C and G are immunostained images for IL-6 showing strong immunoreactivities of IL-6 at the submucosal area in the LL-37 treated bladder. D and H are immunostained images for PTX-3 showing marked increase of PTX-3 positive cells in the LL-37 treated bladder. Lu: lumen, Mu: mucosa, ML: muscle layer.</p

Prevention of Anti-microbial Peptide LL-37-Induced Apoptosis and ATP Release in the Urinary Bladder by a Modified Glycosaminoglycan

<div><p>Interstitial cystitis (IC), often referred to in combination with painful bladder syndrome, is a chronic inflammatory disease of the bladder. Current therapies primarily focus on replenishing urothelial glycosaminoglycan (GAG) layer using GAG analogs and managing pain with supportive therapies. However, the elusive etiology of IC and the lack of animal models to study the disease have been major hurdles developing more effective therapeutics. Previously, we showed an increased urinary concentration of antimicrobial peptide LL-37 in spina bifida patients and used LL-37 to develop a mouse model of cystitis that mimics important clinical findings of IC. Here we investigate (1) the molecular mechanism of LL-37 induced cystitis in cultured human urothelial cells and in mice, (2) the protective effects of GM-0111, a modified GAG, within the context of this mechanism, (3) the physiological and molecular markers that correlate with the severity of the inflammation, and (4) the protective effects of several GAGs using these biomarkers in our LL-37 induced cystitis model. We find that LL-37 quickly induces release of ATP and apoptosis in the urothelium. These changes can be inhibited by a chemically-modified GAG, GM-0111. Furthermore, we also find that GAG analogs provide varying degrees of protection against LL-37 challenge in mice. These findings suggest that GM-0111 and possibly GAG molecules prevent the development of cystitis by blocking the apoptosis and the concurrent release of ATP from the urothelium.</p></div

LL-37 induces apoptotic cell death in human urothelial cells (HUCs).

<p>Cultured HUCs were treated with LL-37 for 15 min at 37°C. HUCs were then collected and labeled with annexin V-FITC (shown in green) and 7-AAD (shown in red). A, Fluorescence microscopy shows the increased number of apoptotic cells in LL-37 treated HUCs (magnification 10<i>x</i>). B, Flow cytometry analysis of HUCs shows that LL-37 induces apoptotic cell death at ≥ 10 µM or higher concentrations of LL-37. *<i>p</i><0.05 and ***<i>p</i><0.001 by Dunnet’s <i>t</i>-test.</p