Ultra-efficient frequency comb generation in AlGaAs-on-insulator microresonators

Recent advances in nonlinear optics have revolutionized integrated photonics, providing on-chip solutions to a wide range of new applications. Currently, state of the art integrated nonlinear photonic devices are mainly based on dielectric material platforms, such as Si₃N₄ and SiO₂. While semiconductor materials feature much higher nonlinear coefficients and convenience in active integration, they have suffered from high waveguide losses that prevent the realization of efficient nonlinear processes on-chip. Here, we challenge this status quo and demonstrate a low loss AlGaAs-on-insulator platform with anomalous dispersion and quality (Q) factors beyond 1.5 × 10⁶. Such a high quality factor, combined with high nonlinear coefficient and small mode volume, enabled us to demonstrate a Kerr frequency comb threshold of only ∼36 µW in a resonator with a 1 THz free spectral range, ∼100 times lower compared to that in previous semiconductor platforms. Moreover, combs with broad spans (>250 nm) have been generated with a pump power of ∼300 µW, which is lower than the threshold power of state-of the-art dielectric micro combs. A soliton-step transition has also been observed for the first time in an AlGaAs resonator

Cellular FLICE-like inhibitory protein (cFLIP) critically maintains apoptotic resistance in human lens epithelial cells

The present study aims to understand the mechanism of the lens epithelial cell’s strong anti-apoptotic capacity and survival in the mature human lens that, on the one hand, maintains lens transparency over several decades, while on the other hand, increases the risk of posterior capsule opacification (PCO). Here we compared FHL124 cells and HeLa cells, spontaneously immortalized epithelial cell lines derived from the human lens and cervical cancer cells, respectively, of their resistance to TNFα-mediated cell death. TNFα plus cycloheximide (CHX) triggered almost all of HeLa cell death. FHL124 cells, however, were unaffected and able to block caspase-8 activation as well as prevent caspase-3 and PARP-1 cleavage. Interestingly, despite spontaneous NFκB and AP-1 activation and upregulation of multiple cell survival/anti-apoptotic genes in both cell types, only FHL124 cells were able to survive the TNFα challenge. After screening and comparing the cell survival genes, cFLIP was found to be highly expressed in FHL124 cells and substantially upregulated by TNFα stimulation. FHL124 cells with a mild cFLIP knockdown manifested a profound apoptotic response to TNFα stimulus similar to HeLa cells. Most importantly, we confirmed these findings in an ex vivo lens capsular bag culture system. In conclusion, our results show that cFLIP is a critical gene that is regulating lens epithelial cell survival

Accumbal Adenosine A2A Receptors Enhance Cognitive Flexibility by Facilitating Strategy Shifting

The deficits of cognitive flexibility (including attentional set-shifting and reversal learning) concomitant with dysfunction of the striatum are observed in several neuropsychiatric disorders. Rodent and human studies have identified the striatum [particularly the dorsomedial striatum (DMS) and nucleus accumbens (NAc)] as the critical locus for control of cognitive flexibility, but the effective neuromodulator and pharmacological control of cognitive flexibility remains to be determined. The adenosine A2A receptors (A2ARs) are highly enriched in the striatopallidal neurons where they integrate dopamine and glutamate signals to modulate several cognitive behaviors, but their contribution to cognitive flexibility control is unclear. In this study, by coupling an automated operant cognitive flexibility task with striatal subregional knockdown (KD) of the A2AR via the Cre-loxP strategy, we demonstrated that NAc A2AR KD improved cognitive flexibility with enhanced attentional set-shifting and reversal learning by decreasing regressive and perseverative errors, respectively. This facilitation was not attributed to mnemonic process or motor activity as NAc A2AR KD did not affect the visual discrimination, lever-pressing acquisition, and locomotor activity, but was associated with increased attention and motivation as evident by the progressive ratio test (PRT). In contrast to NAc A2ARs, DMS A2ARs KD neither affected visual discrimination nor improved set-shifting nor reversal learning, but promoted the effort-related motivation. Thus, NAc and DMS A2ARs exert dissociable controls of cognitive flexibility with NAc A2ARs KD selectively enhancing cognitive flexibility by facilitating strategy shifting with increased motivation/attention

Therapeutic Potential of Targeting the Oncogenic SHP2 Phosphatase

, The Src homology 2 domain containing protein tyrosine phosphatase-2 (SHP2) is an oncogenic phosphatase associated with various kinds of leukemia and solid tumors. Thus, there is substantial interest in developing SHP2 inhibitors as potential anticancer and antileukemia agents. Using a structure-guided and fragment-based library approach, we identified a novel hydroxyindole carboxylic acid-based SHP2 inhibitor 11a-1, with an IC50 value of 200 nM and greater than 5-fold selectivity against 20 mammalian PTPs. Structural and modeling studies reveal that the hydroxyindole carboxylic acid anchors the inhibitor to the SHP2 active site, while interactions of the oxalamide linker and the phenylthiophene tail with residues in the β5–β6 loop contribute to 11a-1’s binding potency and selectivity. Evidence suggests that 11a-1 specifically attenuates the SHP2-dependent signaling inside the cell. Moreover, 11a-1 blocks growth factor mediated Erk1/2 and Akt activation and exhibits excellent antiproliferative activity in lung cancer and breast cancer as well as leukemia cell lines

Circular RNA circPVT1 Promotes Proliferation and Invasion Through Sponging miR-125b and Activating E2F2 Signaling in Non-Small Cell Lung Cancer

Background/Aims: Circular RNAs (circRNAs) are key regulators in the development and progression of human cancers, however its role in non-small cell lung cancer (NSCLC) tumorigenesis is not well understood. The aim of this study is to identify the expression level of circPVT1 in NSCLC and further investigated its functional relevance with NSCLC progression both in vitro and in vivo. Methods: Quantative real-time PCR was used for the measurement of circPVT1 in NSCLC specimens and cell lines. Fluorescence in situ hybridization analysis (FISH) assay was used for the identification of sublocation of circPVT1 in NSCLC cells. Bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation (RIP) were performed to verify the binding of c-Fos at circPVT1 promoter region, and the direct interaction between circPVT1 and miR-125b. Gain- or loss-function assays were performed to evaluate the effects of circPVT1 on cell proliferation and invasion. Western blot and immunohistochemistry assays were performed to detect the protein levels involved in E2F2 pathway. Results: We found that circPVT1 was upregulated in NSCLC specimens and cells. The transcription factor c-Fos binded to the promoter region of circPVT1, resulting in the overexpression of circPVT1 in NSCLC. Knockdown of circPVT1 suppressed NSCLC cell proliferation, migration and invasion, and increased apoptosis. In addition, circPVT1 mediated NSCLC progression via the regulation of E2F2 signaling pathway. More importantly, circPVT1 was predominantly abundant in the cytoplasm of NSCLC cells, and circPVT1 could serve as a competing endogenous RNA to regulate E2F2 expression and tumorigenesis in a miR-125b-dependent manner, which is further verified by using an in vivo xenograft model. Conclusion: circPVT1 promotes NSCLC cell growth and invasion, and may serve as a promising therapeutic target for NSCLC patients. Therefore, silence of circPVT1 could be a future direction to develop a novel treatment strategy

Ultra-efficient frequency comb generation in AlGaAs-on-insulator microresonators

We demonstrated ultra-efficient frequency comb generation in AlGaAs-on-insulator ring resonators that have a quality factor beyond 1.5*10⁶. The threshold power is as low as 36 µW

Ultra-efficient frequency comb generation in AlGaAs-on-insulator microresonators

Recent advances in nonlinear optics have revolutionized integrated photonics, providing on-chip solutions to a wide range of new applications. Currently, state of the art integrated nonlinear photonic devices are mainly based on dielectric material platforms, such as Si₃N₄ and SiO₂. While semiconductor materials feature much higher nonlinear coefficients and convenience in active integration, they have suffered from high waveguide losses that prevent the realization of efficient nonlinear processes on-chip. Here, we challenge this status quo and demonstrate a low loss AlGaAs-on-insulator platform with anomalous dispersion and quality (Q) factors beyond 1.5 × 10⁶. Such a high quality factor, combined with high nonlinear coefficient and small mode volume, enabled us to demonstrate a Kerr frequency comb threshold of only ∼36 µW in a resonator with a 1 THz free spectral range, ∼100 times lower compared to that in previous semiconductor platforms. Moreover, combs with broad spans (>250 nm) have been generated with a pump power of ∼300 µW, which is lower than the threshold power of state-of the-art dielectric micro combs. A soliton-step transition has also been observed for the first time in an AlGaAs resonator