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Abstract Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.

Quantum fluctuations disrupt the cyclic motions of dissipative Kerr solitons (DKSs) in nonlinear optical microresonators and consequently cause timing jitter of the emitted pulse trains. This problem is translated to the performance of several applications that employ DKSs as compact frequency comb sources. Recently, device manufacturing and noise reduction technologies have advanced to unveil the quantum properties of DKSs. Here we investigate the quantum decoherence of DKSs existing in normal-dispersion microresonators known as dark pulses. By virtue of the very large material nonlinearity, we directly observe the quantum decoherence of dark pulses in an AlGaAs-on-insulator microresonator, and the underlying dynamical processes are resolved by injecting stochastic photons into the microresonators. Moreover, phase correlation measurements show that the uniformity of comb spacing of quantum-limited dark pulses is better than 1.2 × 10-16 and 2.5 × 10-13 when normalized to the optical carrier frequencies and repetition frequencies, respectively. Comparing DKSs generated in different material platforms explicitly confirms the advantages of dark pulses over bright solitons in terms of quantum-limited coherence. Our work establishes a critical performance assessment of DKSs, providing guidelines for coherence engineering of chip-scale optical frequency combs.

Optical microresonators with high quality (Q) factors are essential to a wide range of integrated photonic devices. Steady efforts have been directed towards increasing microresonator Q factors across a variety of platforms. With success in reducing microfabrication process-related optical loss as a limitation of Q, the ultimate attainable Q, as determined solely by the constituent microresonator material absorption, has come into focus. Here, we report measurements of the material-limited Q factors in several photonic material platforms. High-Q microresonators are fabricated from thin films of SiO2, Si3N4, Al0.2Ga0.8As, and Ta2O5. By using cavity-enhanced photothermal spectroscopy, the material-limited Q is determined. The method simultaneously measures the Kerr nonlinearity in each material and reveals how material nonlinearity and ultimate Q vary in a complementary fashion across photonic materials. Besides guiding microresonator design and material development in four material platforms, the results help establish performance limits in future photonic integrated systems.

Authors report quantum decoherence of dissipative Kerr solitons in normal-dispersion microresonators, also known as dark pulses. They show the quantum decoherence of dark pulses and their potential advantages over bright solitons in an AlGaAs-on-insulator system.

Inhibition of AMPK leads to metabolic perturbations yet how AMPK is inactivated is not fully understood. Here the authors show protein phosphatase 6 subunit SAPS3 is a negative regulator of AMPK and loss of SAPS3 activates AMPK and protects male mice against overnutrition.

Silicon nitride (SiN) waveguides with ultra-low optical loss enable integrated photonic applications including low noise, narrow linewidth lasers, chip-scale nonlinear photonics, and microwave photonics. Lasers are key components to SiN photonic integrated circuits (PICs), but are difficult to fully integrate with low-index SiN waveguides due to their large mismatch with the high-index III-V gain materials. The recent demonstration of multilayer heterogeneous integration provides a practical solution and enabled the first-generation of lasers fully integrated with SiN waveguides. However, a laser with high device yield and high output power at telecommunication wavelengths, where photonics applications are clustered, is still missing, hindered by large mode transition loss, non-optimized cavity design, and a complicated fabrication process. Here, we report high-performance lasers on SiN with tens of milliwatts output power through the SiN waveguide and sub-kHz fundamental linewidth, addressing all the aforementioned issues. We also show Hertz-level fundamental linewidth lasers are achievable with the developed integration techniques. These lasers, together with high-Q SiN resonators, mark a milestone towards a fully integrated low-noise silicon nitride photonics platform. This laser should find potential applications in LIDAR, microwave photonics and coherent optical communications.

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.

Optical absorption and nonlinear index are important performance drivers in devices like microcombs. Here the authors use resonance-enhanced nonlinear spectroscopy to characterize absorption limits and nonlinear index for some integrated photonic materials.

Achieving high output power and low noise integrated lasers is a major challenge. Here the authors experimentally demonstrate integrated lasers from a Si/SiN heterogeneous platform that shows Hertz-level linewidth, paving the way toward fully integrating low-noise silicon nitride photonics in volume using real devices for lasing.

Here the authors explore the noise spectrum of soliton microcomb when the pump is decoupled from the solitons motion by balancing the Raman shift with the emitted dispersive wave. Based on the analysis of the phase noise and the soliton repetition rate, they identify the uncorrelated thermal fluctuations as underlying mechanism.

Here, the authors demonstrate the use of chaos to obtain 2-octave comb generation. The deformation lifts the circular symmetry and creates chaotic tunneling channels that enable broadband collection of intracavity emission with a single waveguide, introducing a new degree of freedom to microcomb studies.

Despite larger nonlinear coefficients, waveguide losses have prevented using semiconductors instead of dielectric materials for on-chip frequency-comb sources. By significantly reducing waveguide loss, ultra-low-threshold Kerr comb generation is demonstrated in a high-Q AlGaAs-on-insulator microresonator system.

Loss ofMEN1 results in an inherited multiple endocrine neoplastic type 1 syndrome. Here, the authors generate an alveolar type II cell MEN1 knockout mouse model and show that on a Kras mutant background the mice develop lung tumors with features of neuroendocrine differentiation.

In order to study the dynamics of solitons in microresonators, which underlie nonlinear phenomena like Kerr comb generation, both high temporal resolution and long record times are needed. Here, the authors develop a coherent sampling method to directly image the temporal behavior of solitons.

Chip-based microresonator frequency combs are currently limited to the infrared spectral region. Here, the authors generate combs whose center frequency approaches the visible spectrum enabled by combining geometrical and mode-hybridization dispersion control in silica microresonators.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22031-4

Dissipative Kerr solitons in microresonators have recently been shown to generate frequency combs via Cherenkov radiation. Here, Yiet al. demonstrate hysteresis behaviour and a single-mode dispersive wave that can improve the stability of microcombs.

Rational design and synthesis are important for the development of materials for energy applications. Here, the authors sequentially synthesize pyrite structured cobalt phosphosulfide nanoparticles on carbon nanotubes, probing the role of phosphorous substitution on catalyst stability and durability.