Hedgehog signaling in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment

The Hedgehog(HH) signaling pathway plays important roles in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment(TME). Aberrant HH signaling activation may accelerate the growth of gastrointestinal tumors and lead to tumor immune tolerance and drug resistance.The interaction between HH signaling and the TME is intimately involved in these processes, for example, tumor growth, tumor immune tolerance, inflammation, and drug resistance. Evidence indicates that inflammatory factors in the TME, such as interleukin 6(IL-6) and interferon-g(IFN-g), macrophages, and T cell-dependent immune responses, play a vital role in tumor growth by affecting the HH signaling pathway. Moreover, inhibition of proliferating cancer-associated fibroblasts(CAFs) and inflammatory factors can normalize the TME by suppressing HH signaling. Furthermore, aberrant HH signaling activation is favorable to both the proliferation of cancer stem cells(CSCs) and the drug resistance of gastrointestinal tumors. This review discusses the current understanding of the role and mechanism of aberrant HH signaling activation in gastrointestinal carcinogenesis, the gastrointestinal TME,tumor immune tolerance and drug resistance and highlights the underlying therapeutic opportunities.

Dissipative soliton generation and real-time dynamics in microresonator-filtered fiber lasers

Optical frequency combs in microresonators(microcombs)have a wide range of applications in science and technology,due to its compact size and access to considerably larger comb spacing.Despite recent successes,the problems of self-starting,high mode efficiency as well as high output power have not been fully addressed for conventional soliton microcombs.Recent demonstration of laser cavity soliton microcombs by nesting a microresonator into a fiber cavity,shows great potential to solve the problems.Here we study the dissipative soliton generation and interaction dynamics in a microresonator-fltered fiber laser in both theory and experiment.We bring theoretical insight into the mode-locking principle,discuss the parameters effect on soliton properties,and provide experimental guidelines for broadband soliton generation.We predict chirped bright dissipative soliton with flat-top spectral envelope in microresonators with normal dispersion,which is fundamentally forbidden for the externally driven case.Furthermore,we experimentally achieve soliton microcombs with large bandwidth of~10 nm and high mode efficiency of 90.7%.Finally,by taking advantage of an ultrahigh-speed time magnifier,we study the real-time soliton formation and interaction dynamics and experimentally observe soliton Newton's cradle.Our study will benefit the design of the novel,high-efficiency and self-starting microcombs for real-world applications.

Solid-state Mamyshev oscillator

We present the first design and analysis of a solid-state Mamyshev oscillator. We utilize the phase-mismatched cascaded quadratic nonlinear process in a periodically poled lithium niobate waveguide to generate substantial spectral broadening for Mamyshev mode locking. The extensive spectral broadening bridges the two narrowband gain media in the two arms of the same cavity, leading to a broadband mode locking not attainable with either gain medium alone. Two pulses are coupled out of the cavity, and each of the output pulses carries a pulse energy of 25.3 nJ at a repetition rate of 100 MHz. The 10 dB bandwidth of 2.1 THz supports a transform-limited pulse duration of 322 fs, more than 5 times shorter than what can be achieved with either gain medium alone. Finally,effects of group velocity mismatch, group velocity dispersion, and nonlinear saturation on the performance of Mamyshev mode locking are numerically discussed in detail.

Nomogram to Predict Prognosis of Patients with Gastric Cancer after Radical Gastrectomy

Objective To establish an effective prognostic nomogram for patients with gastric cancer after radical gastrectomy.Methods In the present study,we retrospectively analyzed the records of 1635 patients with gastric cancer treated at Changhai Hospital from January 2014 to December 2019.Final independent prognostic factors of overall survival to build a nomogram were screened using univariate and multivariate analyses.The predictive accuracy and discriminating ability of the nomogram were determined using the concordance index(C-index)and calibration curves.The results were validated using bootstrap resampling of 701 patients.The survival curves for low-,middle-,and high-risk patients were used to evaluate the accuracy of the nomogram.Results Multivariate analysis of the primary cohort revealed independent factors for survival as follows:age,sex,body mass index(BMI),depth of tumor invasion(T),lymph node metastasis(N),perineural invasion(PNI),tumor deposits,Alpha fetoprotein(AFP),and lactate dehydrogenase(LDH).Combining these predictors in the nomogram achieved powerful prognostic ability in the training and test sets.The C-index of the training set was 0.772(95%CI,0.748 to 0.796)compared with the C-index values of the AJCC 8^(th)(0.718),T(0.683),N(0.726)and that of the testing set(0.726[95%CI,0.684 to 0.767]),which were significant higher than the C-index values of the TNM system.The calibration curve for probability of survival showed good consistency between predictions made using nomogram compared with actual observations.The survival curves showed significant differences between-high,middle-,and low-risk groups.Conclusion We constructed a more accurate and comprehensive nomogram to predict the prognosis of gastric cancer after surgery,which may serve as a potential tool to guide personalized treatment.