Machine-learning iterative optimization for all polarization-maintaining linear cavity Er:fiber laser.

All polarization-maintaining (PM) linear cavity mode-locked fiber lasers are promising ultrafast laser sources due to their compactness and environmental robustness. Here, we demonstrate a linear cavity fiber laser with all-PM configuration experimentally and investigate the mode-locking formation of the laser using a machine-learning iterative optimization method based on the Gaussian process. The optimization algorithm can converge rapidly after only 30 runs. Using the optimized parameters, we simulate the generation of mode-locked pulses from noise. The output spectrum and pulse energy are highly consistent with the experiment. Furthermore, we describe the intracavity dynamic evolution under group velocity mismatch. We then show that the pulse trapping induced by cross-phase modulation leads to the overcompensated time synchronization between the orthogonally polarized components.

Efficacy and Safety Profile of PD-1 Inhibitors Versus Chemotherapy in the Second-Line Treatment of Advanced Esophageal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Programmed death 1 (PD-1) inhibitors have emerged as the new standard of care for the second-line treatment of advanced esophageal squamous cell carcinoma. There have been lots of research lately concerning the topic. A comprehensive assessment of the efficacy and safety profile between PD-1 inhibitors and chemotherapy is warranted. Hence, we carried out a systematic review and meta-analysis to illustrate this issue. Pubmed, Embase, Cochrane Library, and Embase were searched systematically until May 1, 2022. We extracted data on efficacy and safety and calculated the pooled hazard ratios (HRs) and relative ratios (RRs) with 95% CI using randomized-effect or fixed-effect models. A subgroup analysis was applied to explore the factors modifying the response to PD-1 inhibitors. Ultimately, a total of 5 studies involving 1970 patients were included in our meta-analysis. PD-1 inhibitors group could attain greater overall survival (OS) benefit (HR = 0.73, 95% CI: 0.66-0.81, P < 0.001) and nearly favorable progression-free survival (HR = 0.89, 0.76-1.04, P = 0.13). Treatment-related adverse events (RR = 0.76, 95% CI: 0.64-0.91, P = 0.004) and level 3-5 treatment-related adverse events (RR = 0.40, 95% CI: 0.32-0.49, P < 0.001) were significantly diminished in PD-1 inhibitors groups. Among all modifying factors, programmed death ligand 1 combined positive score was positively associated with the patient's OS. The analysis suggests that PD-1 inhibitors exhibited better survival outcomes and safety profiles than standard-of-care chemotherapy. High levels of programmed death ligand 1 combined positive scores were associated with an enhanced response to PD-1 immunotherapies concerning OS.

Flat visible spectrum by a genetic algorithm optimized photonic crystal fiber in the GHz comb spacing.

Coherent and flat supercontinuum (SC) sources are demanded for applications of metrology, spectroscopy, and bio-imaging. However, the process of SC generation is usually very complicated. We demonstrated a convenient and efficient method based on a genetic algorithm (GA). According to an objective spectrum, this algorithm could reverse-design the geometry of a fiber or waveguide without knowing the specific non-linear processes involved. Using this method, we designed a dispersion-managed photonic crystal fiber (PCF) for SC generation at 1 GHz comb spacing. With an input pulse of ∼150 fs, 450 pJ at 1050 nm, a 3 dB fluctuation spectrum ranging from 510 nm to 850 nm is obtained, which is absolutely fit to the calibration of an astronomical spectrograph.

Targeting KRAS G12C mutations in colorectal cancer.

With the advent of Kirsten rat sarcoma viral oncogene homologue G12C (KRAS G12C) inhibitors, RAS is no longer considered undruggable. For the suppression of RAS, new therapeutic approaches have been suggested. However, current clinical studies have indicated therapeutic resistance after short-lived tumour suppression. According to preclinical studies, this might be associated with acquired genetic alterations, reactivation of downstream pathways, and stimulation for upstream signalling. In this review, we aimed to summarize current approaches for combination therapy to alleviate resistance to KRAS G12C inhibitors in colorectal cancer with a focus on the mechanisms of therapeutic resistance. We also analysed the relationship between various mechanisms and therapeutic resistance.