Watt-level all polarization-maintaining femtosecond fiber laser source at 1100 †nm.

We demonstrate a compact watt-level all polarization-maintaining (PM) femtosecond fiber laser source at 1100 nm. The fiber laser source is seeded by an all PM fiber mode-locked laser employing a nonlinear amplifying loop mirror. The seed laser can generate stable pulses at a fundamental repetition rate of 40.71 MHz with a signal-to-noise rate of >100 dB and an integrated relative intensity noise of only ∼0.061%. After two-stage external amplification and pulse compression, an output power of ∼1.47 W (corresponding to a pulse energy of ∼36.1 nJ) and a pulse duration of ∼251 fs are obtained. The 1100 nm femtosecond fiber laser is then employed as the excitation light source for multicolor multi-photon fluorescence microscopy of Chinese hamster ovary (CHO) cells stably expressing red fluorescent proteins.

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.

Exploring the Role of the Wnt/ß-Catenin Signaling Pathway in Hepatocellular Carcinoma Migration and Tumor Angiogenesis.

Background: Hepatocellular carcinoma (HCC) presents a challenging global health concern due to its high incidence and limited treatment efficacy. Understanding the molecular pathways driving HCC development is crucial for advancing therapeutic strategies and improving patient outcomes. Objective: This study aims to assess the impact of Salinomycin on the Wnt/ß-catenin signaling pathway in hepatocellular carcinoma, exploring its role in tumor migration and angiogenesis. Additionally, to explore the therapeutic potential of targeting this pathway for improving HCC treatment outcomes. Methods: This study employed an in vitro experimental design to investigate the role of the Wnt/ß-catenin signaling pathway in HCC progression. HepG2 cells were cultured in RPMI 1640 medium supplemented with 10% serum, penicillin (100 U/ml), and streptomycin (100 µg/ml). The cells were divided into experimental and control groups for comparative analysis. Salinomycin was administered to inhibit Wnt/ß-catenin pathway activation. The primary outcome measures included the evaluation of cell migration and tumor angiogenesis using cell migration assays and vascular endothelial growth factor (VEGF) expression analysis, respectively. Statistical analysis was performed using the two-tailed Student's t test, with significance set at P < .05. Results: Salinomycin treatment led to a dose-dependent decrease in HCC cell proliferation, with optical density values decreasing as the concentration of Salinomycin increased. Cell migration assays showed inhibited migration in cells treated with Salinomycin compared to controls. Western blot analysis revealed decreased levels of ß-catenin and increased levels of DVL in Salinomycin-treated cells, indicating inhibition of the Wnt/ß-catenin pathway. Furthermore, VEGF expression decreased after Salinomycin treatment, implicating the pathway in tumor angiogenesis. Statistical analysis, including Student's t-test, confirmed significant differences between control and experimental groups (P < .05). Conclusion: The Wnt/ß-catenin signaling pathway plays a significant role in the migration and angiogenesis of HCC when treated with Salinomycin.

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.

Ultrafast fiber laser at 0.9 µm with a gigahertz fundamental repetition rate by a high gain Nd3+-doped phosphate glass fiber.

Fiber lasers, owing to the advantages of excellent beam quality and unique robustness, play a crucial role in lots of fields in modern society. Developing optical glass fibers with superior performance is of fundamental importance for wide applications of fiber lasers. Here, a new Nd3+-doped phosphate single-mode fiber that enables a high gain at 0.9 µm is designed and fabricated. Compared to previous Nd3+-doped silica fibers, the developed phosphate fiber exhibits a significant gain promotion, up to 2.7 dB cm-1 at 915 nm. Configuring in a continuous-wave fiber laser, this phosphate fiber can provide a slope efficiency of 11.2% in a length of only 4.5 cm, about 6 times higher than that of Nd3+-doped silica fiber. To showcase its uniqueness, an ultrafast fiber laser with ultrashort cavity is constructed, such that an ultrashort pulse train with a fundamental repetition rate of up to 1.2 GHz is successfully generated. To the best of our knowledge, this is the highest fundamental repetition rate for mode-locked fiber lasers at this wavelength range - two orders of magnitude higher than that of prior works. These results indicate that this Nd3+-doped phosphate fiber is an effective gain medium for fiber amplifiers and lasers at 0.9 µm, and it is promising for two-photon biophotonics that requires long-term operation with low phototoxicity.

Watt-level gigahertz femtosecond fiber laser system at 920 nm.

We demonstrate a watt-level femtosecond fiber laser system at 0.9 µm with a repetition rate of >1 GHz, which is the highest value reported so far for a fundamental mode-locked fiber laser. The fiber laser system is seeded by a fundamental mode-locked fiber laser constructed with a home-made highly Nd3+-doped fiber. After external amplification and pulse compression, an output power of 1.75 W and a pulse duration of 309 fs are obtained. This compact fiber laser system is expected to be a promising laser source for biological applications, particularly two-photon excitation microscopy.

Shot-Noise Limited Nonlinear Optical Imaging Excited With GHz Femtosecond Pulses and Denoised by Deep-Learning.

Multiphoton fluorescence microscopy excited with femtosecond pulses at high repetition rates, particularly in the range of 100's MHz to GHz, offers an alternative solution to suppress photoinduced damage to biological samples, for example, photobleaching. Here, we demonstrate the use of a U-Net-based deep-learning algorithm for suppressing the inherent shot noise of the two-photon fluorescence images excited with GHz femtosecond pulses. With the trained denoising neural network, the image quality of the representative two-photon fluorescence images of the biological samples is shown to be significantly improved. Moreover, for input raw images with even SNR reduced to -4.76 dB, the trained denoising network can recover the main image structure from noise floor with acceptable fidelity and spatial resolution. It is anticipated that the combination of GHz femtosecond pulses and deep-learning denoising algorithm can be a promising solution for eliminating the trade-off between photoinduced damage and image quality in nonlinear optical imaging platforms.

Behavioral dynamics of neuroprotective macrophage polarization in neuropathic pain observed by GHz femtosecond laser two-photon excitation microscopy.

Macrophage polarization in neurotoxic (M1) or neuroprotective (M2) phenotypes is known to play a significant role in neuropathic pain, but its behavioral dynamics and underlying mechanism remain largely unknown. Two-photon excitation microscopy (2PEM) is a promising functional imaging tool for investigating the mechanism of cellular behavior, as using near-infrared excitation wavelengths is less subjected to light scattering. However, the higher-order photobleaching effect in 2PEM can seriously hamper its applications to long-term live-cell studies. Here, we demonstrate a GHz femtosecond (fs) 2PEM that enables hours-long live-cell imaging of macrophage behavior with reduced higher-order photobleaching effect-by leveraging the repetition rate of fs pulses according to the fluorescence lifetime of fluorophores. Using this new functional 2PEM platform, we measure the polarization characteristics of macrophages, especially the long-term cellular behavior in efferocytosis, unveiling the dynamic mechanism of neuroprotective macrophage polarization in neuropathic pain. These efforts can create new opportunities for understanding long-term cellular dynamic behavior in neuropathic pain, as well as other neurobiological problems, and thus dissecting the underlying complex pathogenesis.

KAT6B May Be Applied as a Potential Therapeutic Target for Glioma.

Glioma is a prevalent malignancy among brain tumors with high modality and low prognosis. Ferroptosis has been identified to play a crucial role in the progression and treatment of cancers. KAT6B, as a histone acetyltransferase, is involved in multiple cancer development. However, the function of KAT6B in glioma is still elusive. Here, we aimed to evaluate the effect of KAT6B on ferroptosis in glioma cells and explored the potential mechanisms. We observed that the expression of KAT6B was enhanced in clinical glioma samples. The viability of glioma cells was repressed by erastin and the overexpression of KAT6B rescued the phenotype in the cells. Meanwhile, the apoptosis of glioma cells was induced by the treatment of erastin, while the overexpression of KAT6B blocked the effect in the cells. The levels of lipid ROS and iron were promoted by the treatment of erastin and the overexpression of KAT6B could reverse the effect in the cells. Mechanically, we identified that the expression of STAT3 was repressed by the KAT6B knockdown in glioma cells. The KAT6B was able to enrich on the promoter of STAT3 in glioma cells. Meanwhile, ChIP assay showed that the knockdown of KAT6B inhibited the enrichment of histone H3 lysine 23 acetylation (H3K23ac) and RNA polymerase II (RNA pol II) on STAT3 promoter in the cells. Depletion of STAT3 reversed KAT6B-regulated viability, apoptosis, and ferroptosis of glioma cells. Thus, we concluded that KAT6B contributes to glioma progression by repressing ferroptosis via epigenetically inducing STAT3.

Site-Specific Variation in Familial Cancer as Suggested by Family History, Multiple Primary Cancer, Age at Onset, and Sex Ratio Associated With Upper, Middle, and Lower Third Esophageal and Gastric Cardia Carcinoma.

BACKGROUND: In China, esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) differ in terms of multiple primary cancer (MPC) and male-to-female sex ratio (MFSR). METHODS: We studied site-specific variation in familial cancer by comparing family history (FH), MPC, age at onset (AO), and MFSR among 8768 patients with ESCC/GCA. RESULTS: ESCC/GCA patients with a positive FH are associated with a significantly higher rate of MPC and a younger AO than those without (sex-specifically: MPC 1.6% vs. 0.7%, P<0.01 and 3.2% vs. 0.8%, P<0.01; AO 53.1 ± 8.1 vs. 54.5 ± 8.2, P=0.000 and 52.9 ± 7.4 vs. 54.0 ± 8.0, P=0.005). Among patients with a positive FH, MPC decreases significantly from upper-, middle-, and lower-third ESCC to GCA (sex-specifically: 53.6%, 1.8%, 1.6%, 0.8%, P=0.000; and 71.4%, 1.5%, 2.2%, 1.6%, P=0.000). From MPC, upper-, middle-, and lower-third ESCC to GCA, AO increased sex-specifically: 51.9 ± 7.2, 52.8 ± 7.9, 52.1 ± 8.3, 54.3 ± 8.4, 55.6 ± 7.6 (P=0.000) and 49.3 ± 6.5, 51.8 ± 9.8, 52.6 ± 7.8, 54.4 ± 8.0, 55.7 ± 7.2 (P=0.000), and FH decreased: 43.8%, 35.1%, 28.2%, 29.5%, 24.4% (P=0.000) and 55.2%, 26.7%, 25.0%, 24.3%, 22.3% (P=0.000). The preponderance of males, smoking, alcohol consumption, and patients ≥50 years old increased from 2.2:1, 1.7:1, 1.0:1, 2.0:1 in ESCC to 6.1:1, 2.8:1, 2.5:1, 4.0:1 in GCA, yet more MPCs were associated with non-preponderant than preponderant counterparts; particularly in GCA, the difference was statistically significant. CONCLUSION: The proportion of familial cancer may decrease from upper-, middle-, and lower-third ESCC to GCA. This entails molecular investigation, and appreciating this may help us devise a better screening strategy or individualize cancer treatment.