Oxygen toxicity causes cyclic damage by destabilizing specific Fe-S cluster-containing protein complexes.

Oxygen is toxic across all three domains of life. Yet, the underlying molecular mechanisms remain largely unknown. Here, we systematically investigate the major cellular pathways affected by excess molecular oxygen. We find that hyperoxia destabilizes a specific subset of Fe-S cluster (ISC)-containing proteins, resulting in impaired diphthamide synthesis, purine metabolism, nucleotide excision repair, and electron transport chain (ETC) function. Our findings translate to primary human lung cells and a mouse model of pulmonary oxygen toxicity. We demonstrate that the ETC is the most vulnerable to damage, resulting in decreased mitochondrial oxygen consumption. This leads to further tissue hyperoxia and cyclic damage of the additional ISC-containing pathways. In support of this model, primary ETC dysfunction in the Ndufs4 KO mouse model causes lung tissue hyperoxia and dramatically increases sensitivity to hyperoxia-mediated ISC damage. This work has important implications for hyperoxia pathologies, including bronchopulmonary dysplasia, ischemia-reperfusion injury, aging, and mitochondrial disorders.

Bright Nonblinking Photoluminescence with Blinking Lifetime from a Nanocavity-Coupled Quantum Dot.

Colloidal quantum dots (QDs) are excellent luminescent nanomaterials for many optoelectronic applications. However, photoluminescence blinking has limited their practical use. Coupling QDs to plasmonic nanostructures shows potential in suppressing blinking. However, the underlying mechanism remains unclear and debated, hampering the development of bright nonblinking dots. Here, by deterministically coupling a QD to a plasmonic nanocavity, we clarify the mechanism and demonstrate unprecedented single-QD brightness. In particular, we report for the first time that a blinking QD could obtain nonblinking photoluminescence with a blinking lifetime through coupling to the nanocavity. We show that the plasmon-enhanced radiative decay outcompetes the nonradiative Auger process, enabling similar quantum yields for charged and neutral excitons in the same dot. Meanwhile, we demonstrate a record photon detection rate of 17 MHz from a colloidal QD, indicating an experimental photon generation rate of more than 500 MHz. These findings pave the way for ultrabright nonblinking QDs, benefiting diverse QD-based applications.

Defocus-integration interferometric scattering microscopy for speckle suppression and enhancing nanoparticle detection on a substrate.

Direct optical detection and imaging of single nanoparticles on a substrate in wide field underpin vast applications across different research fields. However, speckles originating from the unavoidable random surface undulations of the substrate ultimately limit the size of the decipherable nanoparticles by the current optical techniques, including the ultrasensitive interferometric scattering microscopy (iSCAT). Here, we report a defocus-integration iSCAT to suppress the speckle noise and to enhance the detection and imaging of single nanoparticles on an ultra-flat glass substrate and a silicon wafer. In particular, we discover distinct symmetry properties of the scattering phase between the nanoparticle and the surface undulations that cause the speckles. Consequently, we develop the defocus-integration technique to suppress the speckles. We experimentally achieve an enhancement of the signal-to-noise ratio by 6.9 dB for the nanoparticle detection. We demonstrate that the technique is generally applicable for nanoparticles of various materials and for both low and high refractive index substrates.

All-fiber GHz few-cycle pulse generation at 2†µm.

We demonstrate an all-fiber GHz mode-locked laser system with few-cycle duration operating at 2 µm. Based on a dispersion-managed mode-locked oscillator, a multi-stage fiber amplifier, and a nonlinear pulse compressor, the laser system can deliver watt-level few-cycle pulses at a fundamental repetition rate of 1.041 GHz. This 2-µm pulsed laser offers outstanding performance metrics, including a pulse duration of 33 fs (corresponding to ∼5 optical cycles) and an average power of 4.17 W. Moreover, the all-fiber laser system exhibits excellent power stability, and the integrated relative intensity noise (RIN) is only 0.052% (10 Hz-1 MHz). It is anticipated that this new, to the best of our knowledge, laser source is promising for frontier applications, including coherent supercontinuum generation, nonlinear frequency conversion, and laser-material interaction.

Simulation of the nonlinear Kerr and Raman effect with a parallel local time-stepping DGTD solver.

In this paper, an efficient discontinuous Galerkin time-domain (DGTD) method is proposed to solve Maxwell's equations for nonlinear Kerr or Raman media. Based on our previous work, an arbitrary high-order derivatives DGTD method with a local time-stepping scheme is introduced for simulating dynamic optical responses in nonlinear dispersive media such that the nonlinear effects do not impose constraints on the stability conditions for linear subdomains. Therefore, the scheme enables the simulations in the nonlinear and linear media regions with independent time-stepping increments, which greatly improves the efficiency of the time-domain analysis. Moreover, by applying an iteration solution scheme, the proposed method preserves the intrinsic local features, which is favorable for the realization of highly parallelized algorithms. Numerical examples demonstrate the accuracy and the efficiency of our proposed method. We believe the proposed method provides an effective tool for numerical analysis of nonlinear optical phenomena.

1200-W all polarization-maintaining fiber GHz-femtosecond-pulse laser with good beam quality.

In this work, we demonstrate a 1200-W average power all polarization-maintaining (PM) fiber ultrafast laser system operating at 1.0 µm. In accordance with the numerical modeling, the PM fiber laser system is designed and it delivers linearly-polarized femtosecond pulses at a 1.39-GHz fundamental repetition rate, with a maximum output power of 1214 W - to the best of our knowledge, the highest average power from all PM fiber ultrafast laser at 1.0 µm to date. The pulse width can be compressed to ∼800 fs with a beam quality of M2 < 1.1. This kilowatt-class all PM fiber laser system is expected to open new potential for high energy pulse generation through temporal coherent combination and laser ablation using GHz burst fs laser.

Tunable resonance Raman scattering of quantum dots in a nonlinear excitation regime.

Controllable tuning of electron-phonon coupling strength and excited state dynamics is important for the understanding of resonance Raman scattering in low-dimensional semiconductors. Here, we report a significant and reversible field-induced modulation in absolute resonance Raman intensity of quantum dots using ionic liquid gating. Meanwhile, a potential-dependent nonlinear relationship is present between Raman intensity and excitation power density. By exploring the parameter space within a time domain model, we find that the Raman intensity variation is mainly determined by the homogeneous linewidth. We further propose that the Fermi level positions and exciton species play key roles in the excited state decay rates.

Threshold reduction of GHz-repetition-rate passive mode-locking by tapering the gain fiber.

Passively mode-locked fiber lasers with GHz repetition rates have recently attracted significant attention in frontier research areas, including frequency-comb spectroscopy, coherent optical communication, photonic radar, micromachining, etc. In general, the threshold of passive mode-locking increases with the fundamental repetition rate, which is inversely proportional to the cavity length, and this sets a limit on the scalability of the fundamental repetition rate. To overcome this issue, here we propose to reduce the threshold of continuous-wave mode-locking (CWML) by precisely tapering the gain fiber, which can enhance the power density incident on the semiconductor saturable absorber mirror. Assisted by the analysis of guiding property, an experimental scheme is established for tapering standard Yb-doped fibers (125 µm cladding diameter), and tapered Yb-doped fibers with different waist diameters can be fabricated. Using a tapered Yb-doped gain fiber with waist cladding diameter of 90 µm, we are able to achieve CWML with a fundamental repetition rate of 3.3 GHz, and reduce its mode-locking threshold by 31%. More importantly, the optical spectrum of the CWML is found to be broadened with the waist diameter reduction of the gain fiber, which is beneficial for generating shorter transform-limited pulses. The efforts made in this work can provide a promising route to realize stable high-repetition-rate mode-locked fiber lasers with moderate levels of pump power.

Manipulating the polarization dynamics in a >10-GHz Er3+/Yb3+ fiber Fabry-Pérot laser.

In this work, we report on the vector and scalar soliton dynamics that result from inevitable fiber birefringence in an 8-mm Er3+/Yb3+ fiber based Fabry-Férot (FP) laser that has a free spectral range of up to 12.5 GHz. The generation of polarization-evolving vector solitons can largely degrade the performance of application systems, and the underlying mechanisms and manipulation technologies are yet to be explored. To realize the transition from vector to scalar (linearly polarized) state, we here incorporate the polarization selection effect (PSE) in the simulation model and the numerical results verify that only a small amount of PSE is sufficient for manipulating the soliton dynamics. It also reveals that, prominent polarization-dependent intensity discrimination can be acquired via geometry-induced oblique incidence to the Bragg mirror of the semiconductor saturable absorber mirror (SESAM), and we obtain switchable operating states by tilting the SESAM in the experiments. These efforts create a feasible method to manipulate high-repetition-rate pulse and may shed light on understanding the dissipative soliton dynamics in ultrafast fiber FP lasers.

High-speed wavelength-swept femtosecond source from 1055 to 1300†nm using a GHz femtosecond fiber laser.

In this Letter, we demonstrate a high-speed broadband wavelength-swept femtosecond source (WFS) that leverages the soliton self-frequency shift (SSFS) and intensity-wavelength encoding technologies. The optical wavelength of the high-speed WFS can be continuously swept from 1055 nm to nearly 1300 nm at a sweeping rate of 100 kHz. This WFS is especially seeded by a femtosecond mode-locked all-fiber laser at 1055 nm that has a fundamental repetition rate of ∼1.0 GHz, a maximum output power of 7 W, and a compressed pulse width of 220 fs. It is anticipated that this high-speed broadband WFS can be a promising source for applications that require fast wavelength scanning and high-speed data processing.

>10†GHz femtosecond fiber laser system at 2.0†µm.

We demonstrate a high-power 2.0-µm fiber laser system delivering femtosecond pulses with a fundamental repetition rate of >10 GHz, the highest value so far, to the best of our knowledge. The seed is a self-started fundamentally mode-locked Tm-doped fiber laser that has excellent power and spectral stabilities. The laser system can provide an average power of >600 mW, and the use of soliton-effect-based pulse compression allows the achievement of a pulse duration of 163 fs, leading to a compression factor of ∼ 13. It is anticipated that this new high-power femtosecond fiber laser with a 10-GHz-level fundamental repetition rate can serve as a promising light source for various applications, including laser surgery, micromachining, frequency comb spectroscopy, and nonlinear frequency conversion.

Direct Electro Plasmonic and Optic Modulation via a Nanoscopic Electron Reservoir.

Direct electrical tuning of localized plasmons at optical frequencies boasts the fascinating prospects of being ultrafast and energy efficient and having an ultrasmall footprint. However, the prospects are obscured by the grand challenge of effectively modulating the very large number of conduction electrons in three-dimensional metallic structures. Here we propose the concept of nanoscopic electron reservoir (NER) for direct electro plasmonic and electro-optic modulation. A NER is a few-to-ten-nanometer size metal feature on a metal host and supports a localized plasmon mode. We provide a general guideline to construct highly electrically susceptible NERs and theoretically demonstrate pronounced direct electrical tuning of the plasmon mode by exploiting the nonclassical effects of conduction electrons. Moreover, we show the electro-plasmonic tuning can be efficiently translated into modulation of optical scattering by utilizing the antenna effect of the metal host for the NER. Our work extends the landscape of electro plasmonic modulation and opens appealing new opportunities for quantum plasmonics.

Optical Fingerprint of Flat Substrate Surface and Marker-Free Lateral Displacement Detection with Angstrom-Level Precision.

We report that flat substrates such as glass coverslips with surface roughness well below 0.5 nm feature notable speckle patterns when observed with high-sensitivity interference microscopy. We uncover that these speckle patterns unambiguously originate from the subnanometer surface undulations, and develop an intuitive model to illustrate how subnanometer nonresonant dielectric features could generate pronounced interference contrast in the far field. We introduce the concept of optical fingerprint for the deterministic speckle pattern associated with a particular substrate surface area and intentionally enhance the speckle amplitudes for potential applications. We demonstrate such optical fingerprints can be leveraged for reproducible position identification and marker-free lateral displacement detection with an experimental precision of 0.22 nm. The reproducible position identification allows us to detect new nanoscopic features developed during laborious processes performed outside of the microscope. The demonstrated capability for ultrasensitive displacement detection may find applications in the semiconductor industry and superresolution optical microscopy.

Vector soliton dynamics in a high-repetition-rate fiber laser.

The existence of vector solitons that arise from the birefringence nature of optical fibers has been increasingly of interest for the stability of mode-locked fiber lasers, particularly for those operating in the high-fundamental-repetition-rate regime, where a large amount of fiber birefringence is required to restore the phase relation between the orthogonally polarized vector solitons, resulting in stable mode-locking free of polarization rotation. These vector solitons can exhibit diverse time-varying polarization dynamics, which prevent industrial and scientific applications requiring stable and uniform pulse trains at high fundamental repetition rates. This pressing issue, however, has so far been rarely studied. To this end, here we theoretically and experimentally dissect the formation of vector solitons in a GHz-repetition-rate fiber laser and investigate effective methods for suppressing roundtrip-to-roundtrip polarization dynamics. Our numerical model can predict both dynamic and stable regimes of high-repetition-rate mode-locking by varying the amount of fiber birefringence, resulting in the polarization rotation vector soliton (PRVS) and linearly polarized soliton (LPS), respectively. These dynamic behaviors are further studied by using an analytical approach. Interestingly, our theoretical results indicate a cavity-induced locking effect, which can be a complementary soliton trapping mechanism for the co-propagating solitons. Finally, these theoretical predications are experimentally verified, and we obtain both PRVS and LPS by adjusting the intracavity fiber birefringence.

High-power femtosecond all-fiber laser system at 1.5 µm with a fundamental repetition rate of 4.9 GHz.

In this Letter, we demonstrate a high-power femtosecond all-fiber laser system at 1.5 µm that operates at a fundamental repetition rate of up to 4.9 GHz. This high repetition rate laser system delivers an average power of 10 W and a pulsewidth of 63 fs in an all-fiber configuration-the best overall performance at 1.5 µm, so far, in terms of the all-fiber design, high average power, short pulsewidth, and high fundamental repetition rate. Integrated from 10 Hz to 10 MHz, this high-power femtosecond all-fiber laser system exhibits a relative intensity noise of only 0.4%. It is anticipated that this femtosecond laser system is promising for various applications, such as high-speed micromachining, wide-field multiphoton bioimaging, and nonlinear optics.

NEIL3 may act as a potential prognostic biomarker for lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death. This study aimed to develop and validate reliable prognostic biomarkers and signature. METHODS: Differentially expressed genes were identified based on three Gene Expression Omnibus (GEO) datasets. Based on 1052 samples' data from our cohort, GEO and The Cancer Genome Atlas, we explored the relationship of clinicopathological features and NEIL3 expression to determine clinical effect of NEIL3 in LUAD. Western blotting (22 pairs of tumor and normal tissues), Real-time quantitative PCR (19 pairs of tumor and normal tissues), and immunohistochemical analyses (406-tumor tissues subjected to microarray) were conducted. TIMER and ImmuCellAI analyzed relationship between NEIL3 expression and the abundance of tumor-infiltrating immune cells in LUAD. The co-expressed-gene prognostic signature was established based on the Cox regression analysis. RESULTS: This study identified 502 common differentially expressed genes and confirmed that NEIL3 was significantly overexpressed in LUAD samples (P < 0.001). Increased NEIL3 expression was related to advanced stage, larger tumor size and poor overall survival (p < 0.001) in three LUAD cohorts. The proportions of natural T regulatory cells and induced T regulatory cells increased in the high NEIL3 group, whereas those of B cells, Th17 cells and dendritic cells decreased. Gene set enrichment analysis indicated that NEIL3 may activate cell cycle progression and P53 signaling pathway, leading to poor outcomes. We identified nine prognosis-associated hub genes among 370 genes co-expressed with NEIL3. A 10-gene prognostic signature including NEIL3 and nine key co-expressed genes was constructed. Higher risk-score was correlated with more advanced stage, larger tumor size and worse outcome (p < 0.05). Finally, the signature was verified in test cohort (GSE50081) with superior diagnostic accuracy. CONCLUSIONS: This study suggested that NEIL3 has the potential to be an immune-related therapeutic target and an independent predictor of LUAD prognosis. We also developed a prognostic signature for LUAD with a precise diagnostic accuracy.

General Framework of Canonical Quasinormal Mode Analysis for Extreme Nano-optics.

Optical phenomena associated with an extremely localized field should be understood with considerations of nonlocal and quantum effects, which pose a hurdle to conceptualize the physics with a picture of eigenmodes. Here we first propose a generalized Lorentz model to describe general nonlocal media under linear mean-field approximation and formulate source-free Maxwell's equations as a linear eigenvalue problem to define the quasinormal modes. Then we introduce an orthonormalization scheme for the modes and establish a canonical quasinormal mode framework for general nonlocal media. Explicit formalisms for metals described by a quantum hydrodynamic model and polar dielectrics with nonlocal response are exemplified. The framework enables for the first time a direct modal analysis of mode transition in the quantum tunneling regime and provides physical insights beyond usual far-field spectroscopic analysis. Applied to nonlocal polar dielectrics, the framework also unveils the important roles of longitudinal phonon polaritons in optical response.

Bright Optical Eigenmode of 1 nm

We report on the discovery and rationale to devise bright single optical eigenmodes that feature quantum-optical mode volumes of about 1 nm^{3}. Our findings rely on the development and application of a quasinormal mode theory that self-consistently treats fields and electron nonlocality, spill-out, and Landau damping around atomistic protrusions on a metallic nanoantenna. By outpacing Landau damping with radiation via properly designed antenna modes, the extremely localized modes become bright with radiation efficiencies reaching 30% and could provide up to 4×10^{7} times intensity enhancement.

Colorectal cancer-derived small extracellular vesicles establish an inflammatory premetastatic niche in liver metastasis.

Liver metastases develop in more than half of the patients with colorectal cancer (CRC) and are associated with a poor prognosis. The factors influencing liver metastasis of CRC are poorly characterized, but this information is urgently needed. We have now discovered that small extracellular vesicles (sEVs; exosomes) derived from CRC can be specifically targeted to liver tissue and induce liver macrophage polarization toward an interleukin-6 (IL-6)-secreting proinflammatory phenotype. More importantly, we found that microRNA-21-5p (miR-21) was highly enriched in CRC-derived sEVs and was essential for creating a liver proinflammatory phenotype and liver metastasis of CRC. Silencing either miR-21 in CRC-sEVs or Toll-like receptor 7 (TLR7) in macrophages, to which miR-21 binds, abolished CRC-sEVs' induction of proinflammatory macrophages. Furthermore, miR-21 expression in plasma-derived sEVs was positively correlated with liver metastasis in CRC patients. Collectively, our data demonstrate a pivotal role of CRC-sEVs in promoting liver metastasis by inducing an inflammatory premetastatic niche through the miR-21-TLR7-IL-6 axis. Thus, sEVs-miR-21 represents a potential prognostic marker and therapeutic target for CRC patients with liver metastasis.

Imaging method based on the combination of microlens arrays and aperture arrays.

Conventional imaging methods will cause a serious distortion for large object plane imaging with a limited object-to-sensor distance (OTSD). Here, we propose an imaging method based on the combination of microlens arrays and aperture arrays to realize the low-distortion, large object plane imaging range (OPIR) and compact design imaging at a close OTSD. Two-stage microlens arrays are utilized to reduce the distance between the object and sensor with low distortion, and two-stage aperture arrays are sandwiched between the microlens arrays to eliminate stray light between different microlenses. The theoretical analysis and simulation results indicate that our proposed method can realize low-distortion imaging with a large OPIR when the OTSD is seriously limited. This imaging method can be used widely in small-size optical devices where the OTSD is extremely limited.