High-visibility energy-time entanglement system enabled by a low-loss silicon-integrated platform.

Energy-time (E-T) entanglement is widely employed in long-distance quantum entanglement distribution due to its strong robustness against transmission fluctuations. In this Letter, we report what we believe to be the first silicon monolithically integrated E-T entanglement system, which integrates the photon sources, wavelength demultiplexers, and Franson interferometers on a single chip. Also, by utilizing low-loss multimode waveguides in Franson interferometers, we measured an on-chip quantum interference visibility of 99.66% (±0.47%), to our knowledge one of the highest values for integrated E-T entanglement systems reported to date. The quantum interference after 1- and 5-km fiber propagation shows visibilities of 96.72% (±0.78%) and 97.46% (±1.23%), respectively. These results demonstrate the potential of using silicon monolithic integration for advance E-T entanglement-based quantum communication networks.

Scalable integrated two-dimensional Fourier-transform spectrometry.

Integrated spectrometers offer the advantages of small sizes and high portability, enabling new applications in industrial development and scientific research. Integrated Fourier-transform spectrometers (FTS) have the potential to realize a high signal-to-noise ratio but typically have a trade-off between the resolution and bandwidth. Here, we propose and demonstrate the concept of the two-dimensional FTS (2D-FTS) to circumvent the trade-off and improve scalability. The core idea is to utilize 2D Fourier transform instead of 1D Fourier transform to rebuild spectra. By combining a tunable FTS and a spatial heterodyne spectrometer, the interferogram becomes a 2D pattern with variations of heating power and arm lengths. All wavelengths are mapped to a cluster of spots in the 2D Fourier map beyond the free-spectral-range limit. At the Rayleigh criterion, the demonstrated resolution is 250 pm over a 200-nm bandwidth. The resolution can be enhanced to 125 pm using the computational method.

TFEB SUMOylation in macrophages accelerates atherosclerosis by promoting the formation of foam cells through inhibiting lysosomal activity.

Atherosclerosis (AS) is a serious cardiovascular disease. One of its hallmarks is hyperlipidemia. Inhibiting the formation of macrophage foam cells is critical for alleviating AS. Transcription factor EB (TFEB) can limit the formation of macrophage foam cells by upregulating lysosomal activity. We examined whether TFEB SUMOylation is involved in this progress during AS. In this study, we investigated the role of TFEB SUMOylation in macrophages in AS using TFEB SUMOylation deficiency Ldlr-/- (TFEB-KR: Ldlr-/-) transgenic mice and TFEB-KR bone marrow-derived macrophages. We observed that TFEB-KR: Ldlr-/- atherosclerotic mice had thinner plaques and macrophages with higher lysosomal activity when compared to WT: Ldlr-/- mice. TFEB SUMOylation in macrophages decreased after oxidized low-density lipoprotein (OxLDL) treatment in vitro. Compared with wild type macrophages, TFEB-KR macrophages exhibited less lipid deposition after OxLDL treatment. Our study demonstrated that in AS, deSUMOylation of TFEB could inhibit the formation of macrophage foam cells through enhancing lysosomal biogenesis and autophagy, further reducing the accumulation of lipids in macrophages, and ultimately alleviating the development of AS. Thus, TFEB SUMOylation can be a switch to modulate macrophage foam cells formation and used as a potential target for AS therapy.

Breaking the resolution-bandwidth limit of chip-scale spectrometry by harnessing a dispersion-engineered photonic molecule.

The chip-scale integration of optical spectrometers may offer new opportunities for in situ bio-chemical analysis, remote sensing, and intelligent health care. The miniaturization of integrated spectrometers faces the challenge of an inherent trade-off between spectral resolutions and working bandwidths. Typically, a high resolution requires long optical paths, which in turn reduces the free-spectral range (FSR). In this paper, we propose and demonstrate a ground-breaking spectrometer design beyond the resolution-bandwidth limit. We tailor the dispersion of mode splitting in a photonic molecule to identify the spectral information at different FSRs. When tuning over a single FSR, each wavelength channel is encoded with a unique scanning trace, which enables the decorrelation over the whole bandwidth spanning multiple FSRs. Fourier analysis reveals that each left singular vector of the transmission matrix is mapped to a unique frequency component of the recorded output signal with a high sideband suppression ratio. Thus, unknown input spectra can be retrieved by solving a linear inverse problem with iterative optimizations. Experimental results demonstrate that this approach can resolve any arbitrary spectra with discrete, continuous, or hybrid features. An ultrahigh resolution of <40 pm is achieved throughout an ultrabroad bandwidth of >100 nm far exceeding the narrow FSR. An ultralarge wavelength-channel capacity of 2501 is supported by a single spatial channel within an ultrasmall footprint (≈60 × 60 µm2), which represents, to the best of our knowledge, the highest channel-to-footprint ratio (≈0.69 µm-2) and spectral-to-spatial ratio (>2501) ever demonstrated to date.

Compact integrated mode-size converter using a broadband ultralow-loss parabolic-mirror collimator.

In this Letter, we propose and demonstrate an integrated mode-size converter (MSC) with a compact footprint, low losses, and a broad bandwidth. By exploiting a parabolic mirror, the divergent light from a narrow waveguide (450 nm) is collimated to match the mode size of a wide waveguide (10 µm). The measured insertion loss (IL) is ≈ 0.15 dB over a 100-nm bandwidth. The mode-size conversion is achieved with a footprint as small as ≈ 20 × 32 µm2, which is much shorter than the linear taper length required to attain the same level of losses.

Mitotic SENP3 activation couples with cGAS signaling in tumor cells to stimulate anti-tumor immunity.

Our previous studies show that the mitotic phosphorylation of SUMO-specific protease 3 (SENP3) can inhibit its de-SUMOylation activity in G2/M phase of the cell cycle. Inhibition of SENP3 plays a critical role in the correct separation of sister chromatids in mitosis. The mutation of mitotic SENP3 phosphorylation causes chromosome instability and promotes tumorigenesis. In this study, we find that the mutation of mitotic SENP3 phosphorylation in tumor cells can suppress tumor growth in immune-competent mouse model. We further detect an increase of CD8+ T cell infiltration in the tumors, which is essential for the anti-tumor effect in immune-competent mouse model. Moreover, we find that mitotic SENP3 activation increases micronuclei formation, which can activate cGAS signaling-dependent innate immune response. We confirmed that cGAS signaling mediates the mitotic SENP3 activation-induced anti-tumor immunity. We further show that p53 responding to DNA damage activates mitotic SENP3 by inhibiting phosphorylation, and further increases cellular senescence as well as the related innate immune response in tumor cells. Furthermore, TCGA database demonstrates that the SENP3 expression positively correlates with the induction of innate immune response as well as the survival of the p53 mutant pancreatic cancer patients. Together, these data reveal that mitotic SENP3 activation in tumor cells can promote host anti-tumor immune response by coupling with cGAS signaling.

SENP1-Sirt3 signaling promotes α-ketoglutarate production during M2 macrophage polarization.

The metabolic program is altered during macrophage activation and influences macrophage polarization. Glutaminolysis promotes accumulation of α-ketoglutarate (αKG), leading to Jumonji domain-containing protein D3 (Jmjd3)-dependent demethylation at H3K27me3 during M2 polarization of macrophages. However, it remains unclear how αKG accumulation is regulated during M2 polarization of macrophages. This study shows that SENP1-Sirt3 signaling controls glutaminolysis, leading to αKG accumulation during IL-4-stimulated M2 polarization. Activation of the SENP1-Sirt3 axis augments M2 macrophage polarization through the accumulation of αKG via glutaminolysis. We also identify glutamate dehydrogenase 1 (GLUD1) as an acetylated protein in mitochondria. The SENP1-Sirt3 axis deacetylates GLUD1 and increases its activity in glutaminolysis to promote αKG production, leading to M2 polarization of macrophages. Therefore, SENP1-Sirt3 signaling plays a critical role in αKG accumulation via glutaminolysis to promote M2 polarization.

Polarization-independent waveguide grating coupler using an optimized polysilicon overlay.

We propose and validate a new, to the best of our knowledge, approach to designing a polarization-independent waveguide grating coupler, using an optimized polysilicon overlay on a silicon grating structure. Simulations predicted coupling efficiencies of about -3.6 dB and -3.5 dB for TE and TM polarizations, respectively. The devices were fabricated using photolithography in a multi-project wafer fabrication service by a commercial foundry and have measured coupling losses of -3.96 dB for TE polarization and -3.93 dB for TM polarization.

Glucose limitation activates AMPK coupled SENP1-Sirt3 signalling in mitochondria for T cell memory development.

Metabolic programming and mitochondrial dynamics along with T cell differentiation affect T cell fate and memory development; however, how to control metabolic reprogramming and mitochondrial dynamics in T cell memory development is unclear. Here, we provide evidence that the SUMO protease SENP1 promotes T cell memory development via Sirt3 deSUMOylation. SENP1-Sirt3 signalling augments the deacetylase activity of Sirt3, promoting both OXPHOS and mitochondrial fusion. Mechanistically, SENP1 activates Sirt3 deacetylase activity in T cell mitochondria, leading to reduction of the acetylation of mitochondrial metalloprotease YME1L1. Consequently, deacetylation of YME1L1 suppresses its activity on OPA1 cleavage to facilitate mitochondrial fusion, which results in T cell survival and promotes T cell memory development. We also show that the glycolytic intermediate fructose-1,6-bisphosphate (FBP) as a negative regulator suppresses AMPK-mediated activation of the SENP1-Sirt3 axis and reduces memory development. Moreover, glucose limitation reduces FBP production and activates AMPK during T cell memory development. These data show that glucose limitation activates AMPK and the subsequent SENP1-Sirt3 signalling for T cell memory development.

SUMOylation of MCL1 protein enhances its stability by regulating the ubiquitin-proteasome pathway.

In cancers, apoptosis evasion through dysregulation of pro-apoptotic and anti-apoptotic intracellular signals is a recurring event. Accordingly, selective inhibition of specific proteins represents an exciting therapeutic opportunity. Myeloid cell leukemia 1 (MCL1) is an anti-apoptotic protein of the BCL-2 family, which is overexpressed in many cancers. Here, we demonstrate that MCL1 can be modified by the small ubiquitin-like modifier (SUMO) at K234 and K238 sites. The SUMOylation of MCL1 can improve its stability by inhibiting the MCL1 ubiquitin-proteasome pathway mediated by the Tripartite motif-containing 11 (TRIM11, a novel MCL1 ubiquitin E3 ligase that we identify in this study). Moreover, SUMOylation of MCL1 increases the proliferation of cancer cells by inhibiting apoptosis. These results suggest that the SUMOylation of MCL1 may play a significant role in the regulation of its function.

P53 suppresses SENP3 phosphorylation to mediate G2 checkpoint.

In response to DNA damage, p53-mediated signaling is regulated by protein phosphorylation and ubiquitination to precisely control G2 checkpoint. Here we demonstrated that protein SUMOylation also engaged in regulation of p53-mediated G2 checkpoint. We found that G2 DNA damage suppressed SENP3 phosphorylation at G2/M phases in p53-dependent manner. We further found that the suppression of SENP3 phosphorylation was crucial for efficient DNA damage/p53-induced G2 checkpoint and G2 arrest. Mechanistically, we identified Cdh1, a subunit of APC/C complex, was a SUMOylated protein at G2/M phase. SENP3 could de-SUMOylate Cdh1. DNA damage/p53-induced suppression of SENP3 phosphorylation activated SENP3 de-SUMOylation of Cdh. De-SUMOylation promoted Cdh1 de-phosphorylation by phosphatase Cdc14B, and then activated APC/CCdh1 E3 ligase activity to ubiquitate and degrade Polo-like kinase 1 (Plk1) in process of G2 checkpoint. These data reveal that p53-mediated inhibition of SENP3 phosphorylation regulates the activation of Cdc14b-APC/CCdh1-Plk1 axis to control DNA damage-induced G2 checkpoint.

Association between EHBP1 rs721048(A>G) polymorphism and prostate cancer susceptibility: a meta-analysis of 17 studies involving 150,678 subjects.

BACKGROUND: EHBP1 rs721048(A) was first identified as a prostate cancer (PCa) risk in Caucasians by genome-wide association study, but subsequent replication studies involving Caucasian and other ethnicities did not produce consistent results. The aim of this study was to obtain a more definite association between rs721048(A) and PCa risk. METHODS: We comprehensively searched several databases updated to September 2014, including PubMed, Web of Science, EBSCO, and Google Scholar. Two authors independently screened and reviewed the eligibility of each study. The quality of the included studies was assessed by the Newcastle-Ottawa scale. The association of rs721048(A) and PCa risk was assessed by pooling odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of 17 studies, including 48,135 cases and 102,543 controls, published between 2008 and 2014 were included in the meta-analysis. Overall, the pooled analysis demonstrated that rs721048(A) was significantly associated with the risk of PCa under the allele model (OR=1.14, 95% CI=1.11-1.17, P=0.000). Subgroup analysis based on ethnicity revealed a significant association between rs721048(A) and PCa in Caucasian (OR=1.14, 95% CI=1.11-1.16, P=0.000), African descent (OR=1.11, 95% CI=1.01-1.23, P=0.025), and Asian (OR=1.35, 95% CI=1.12-1.64, P=0.002). CONCLUSION: Our results provided strong evidence that rs721048(A) could be a risk factor for PCa.

Association of monocyte chemoattractant protein-1 (MCP-1)-2518A>G polymorphism with susceptibility to coronary artery disease: a meta-analysis.

We attempted to systematically elucidate the association between monocyte chemoattractant protein-1 (MCP-1) -2518A>G polymorphism and risk of coronary artery disease (CAD). Eligible studies were identified through PubMed, EBSCO, and Web of Science Databases. The magnitude of MCP-1 polymorphism effect and its possible mode of action on CAD were estimated. The odds ratio (OR) with 95% confidence intervals (CI) were pooled in a specific genetic model to assess the association. A total of 21 studies were involved. There was significant gene effect on CAD risk in the overall population (likelihood ratio test: p < 0.0001). Patients with GG and AG genotypes had 1.435 (95% CI: 1.183-1.740) and 1.087 (95% CI: 1.008-1.172) times higher risk of CAD than those with AA genotype. These gene effects suggested a recessive model to be appropriate. The pooled OR was 1.362 (95% CI: 1.137-1.631; puncorrected = 0.001, pFDR = 0.005) in the recessive model. In the ethnicity-stratified analysis, significant association was observed in the Caucasian population (OR = 1.492; 95% CI: 1.106-2.014; puncorrected = 0.009, pFDR = 0.015), whereas no statistical significant association was detected in the Asian population (adjusted p = 0.124). The results suggested that MCP-1 -2518A>G polymorphism may be associated with susceptibility to CAD, especially in Caucasians.

FOXK2 transcription factor suppresses ERα-positive breast cancer cell growth through down-regulating the stability of ERα via mechanism involving BRCA1/BARD1.

Estrogen receptors (ERs) are critical regulators of breast cancer development. Identification of molecules that regulate the function of ERs may facilitate the development of more effective breast cancer treatment strategies. In this study, we showed that the forkhead transcription factor FOXK2 interacted with ERα, and inhibited ERα-regulated transcriptional activities by enhancing the ubiquitin-mediated degradation of ERα. This process involved the interaction between FOXK2 and BRCA1/BARD1, the E3 ubiquitin ligase of ERα. FOXK2 interacted with BARD1 and acted as a scaffold protein for BRCA1/BARD1 and ERα, leading to enhanced degradation of ERα, which eventually accounted for its decreased transcriptional activity. Consistent with these observations, overexpression of FOXK2 inhibited the transcriptional activity of ERα, decreased the transcription of ERα target genes, and suppressed the proliferation of ERα-positive breast cancer cells. In contract, knockdown of FOXK2 in MCF-7 cells promoted cell proliferation. However, when ERα was also knocked down, knockdown of FOXK2 had no effect on cell proliferation. These findings suggested that FOXK2 might act as a negative regulator of ERα, and its association with both ERα and BRCA1/BARD1 could lead to the down-regulation of ERα transcriptional activity, effectively regulating the function of ERα.