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Dissipative quadratic solitons (DQSs), enabled by nonlinearity engineering through cascaded quadratic processes, have remained a central theoretical prediction in nonlinear optics since their proposal in 1997. Despite their predicted ultralow operational thresholds, remarkable tunability, and potential for spectral extension into unconventional wavelengths, their experimental realization has remained elusive. Here, we demonstrate bright, dual-color DQS generation in the normal dispersion regime, in strong agreement with the proposed theoretical framework. Furthermore, by simply adjusting the nonlinear crystal temperature - without any structural modification - we reverse the sign of the effective nonlinearity and switch from bright DQS to platicon generation in situ. This work not only advances the fundamental understanding of dissipative solitons but also establishes a practical pathway for ultralow-threshold frequency comb generation at unconventional wavelengths, with broad implications for applications such as atomic clocks, optical coherence tomography, and astrocombs. In this work, the authors demonstrate nonlinearity-engineered dissipative quadratic solitons (DQS) for the first time. Moreover, they achieve an in-situ sign reversal of the effective nonlinearity, enabling a transition from bright DQS to platicon generation without requiring any dispersion engineering.

Dissipative Kerr soliton (DKS) frequency combs—also known as microcombs—have arguably created a new field in cavity nonlinear photonics, with a strong cross-fertilization between theoretical, experimental, and technological research. Spatiotemporal mode-locking (STML) not only adds new degrees of freedom to ultrafast laser technology, but also provides new insights for implementing analogue computers and heuristic optimizers with photonics. Here, we combine the principles of DKS and STML to demonstrate the STML DKS by developing an unexplored ultrahigh-quality-factor Fabry–Pérot (FP) mesoresonator based on graded index multimode fiber (GRIN-MMF). Complementing the two-step pumping scheme with a cavity stress tuning method, we can selectively excite either the eigenmode DKS or the STML DKS. Furthermore, we demonstrate an ultralow noise microcomb that enhances the photonic flywheel performance in both the fundamental comb linewidth and DKS timing jitter. The demonstrated fundamental comb linewidth of 400 mHz and DKS timing jitter of 500 attosecond (averaging times up to 25 μs) represent improvements of 25× and 2.5×, respectively, from the state-of-the-art. Our results show the potential of GRIN-MMF FP mesoresonators as an ideal testbed for high-dimensional nonlinear cavity dynamics and photonic flywheel with ultrahigh coherence and ultralow timing jitter. Here the authors demonstrate spatiotemporal mode-locked dissipative Kerr soliton and enhanced photonic flywheel performances in both the fundamental comb linewidth and DKS timing jitter.

Dissipative Kerr soliton (DKS) microcomb has emerged as an enabling technology that revolutionizes a wide range of applications in both basic science and technological innovation. Reliable turnkey operation with sub-optical-cycle and sub-femtosecond timing jitter is key to the success of many intriguing microcomb applications at the intersection of ultrafast optics and microwave electronics. Here we propose an approach and demonstrate the first turnkey Brillouin-DKS frequency comb to the best of our knowledge. Our microresonator-filtered laser design offers essential benefits, including phase insensitivity, self-healing capability, deterministic selection of the DKS state, and access to the ultralow noise comb state. The demonstrated turnkey Brillouin-DKS frequency comb achieves a fundamental comb linewidth of 100 mHz and DKS timing jitter of 1 femtosecond for averaging times up to 56 μs. The approach is universal and generalizable to various device platforms for user-friendly and field-deployable comb devices. Here the authors demonstrate a universal approach to achieve turnkey dissipative Kerr soliton (DKS) frequency comb. Phase insensitivity, self-healing capability, deterministic selection of DKS state, and access to ultralow noise are all successfully accomplished.

Adenocarcinoma of the gastroesophageal junction (AEG) has become increasingly common in Western and Asian populations. Surgical resection is the mainstay of treatment for AEG; however, determining the distance from the upper edge of the tumor to the esophageal margin (PM) is essential for accurate prognosis. Despite the relevance of these studies, most have been retrospective and vary widely in their conclusions. The PM is now widely accepted to have an impact on patient outcomes but can be masked by TNM at later stages. Extended PM is associated with improved outcomes, but the optimal PM is uncertain. Academics continue to debate the surgical route, extent of lymphadenectomy, preoperative tumor size assessment, intraoperative cryosection, neoadjuvant therapy, and other aspects to further ensure a negative margin in patients with gastroesophageal adenocarcinoma. This review summarizes and evaluates the findings from these studies and suggests that the choice of approach for patients with adenocarcinoma of the esophagogastric junction should take into account the extent of esophagectomy and lymphadenectomy. Although several guidelines and reviews recommend the routine use of intraoperative cryosections to evaluate surgical margins, its generalizability is limited. Furthermore, neoadjuvant chemotherapy and radiotherapy are more likely to increase the R0 resection rate. In particular, intraoperative cryosections and neoadjuvant chemoradiotherapy were found to be more effective for achieving negative resection margins in signet ring cell carcinoma.

Trastuzumab emtansine (T-DM1), an antibody-drug conjugate consisted of the HER2-targeted monoclonal antibody trastuzumab and the tubulin inhibitor emtansine, has shown potent therapeutic value in HER2-positive breast cancer (BC). However, a clinical trial indicated that T-DM1 exerts a limited effect on HER2-positive gastric cancer (GC), but the underlying mechanism is inconclusive. Our research attempted to reveal the probable mechanism and role of autophagy in T-DM1-treated HER2-positive GC. In this study, our results showed that T-DM1 induced apoptosis and exhibited potent therapeutic efficacy in HER2-positive GC cells. In addition, autophagosomes were observed by transmission electron microscopy. Autophagy was markedly activated and exhibited the three characterized gradations of autophagic flux, consisting of the formation of autophagosomes, the fusion of autophagosomes with lysosomes, and the deterioration of autophagosomes in autolysosomes. More importantly, autophagic inhibition by the suppressors 3-methyladenine (3-MA) and LY294002 significantly potentiated cytotoxicity and apoptosis in HER2-positive GC cells in vitro, while the combined use of LY294002 and T-DM1 elicited potent anti-GC efficacy in vivo. In mechanistic experiments, immunoblot analysis indicated the downregulated levels of Akt, mTOR, and P70S6K and confocal microscopy analysis clearly showed that autophagic inhibition promoted the fusion of T-DM1 molecules with lysosomes in GC cells. In conclusion, our research demonstrated that T-DM1 induced apoptosis as well as cytoprotective autophagy, and autophagic inhibition could potentiate the antitumor effect of T-DM1 on HER2-positive GC. Furthermore, autophagic inhibition might increase the fusion of T-DM1 with lysosomes, which might accelerate the release of the cytotoxic molecule emtansine from the T-DM1 conjugate. These findings highlight a promising therapeutic strategy that combines T-DM1 with an autophagy inhibitor to treat HER-positive GC more efficiently.

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-filtered 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.We theoretically and experimentally study soliton generation and real-time dynamics via time magnifier in microresonator-filtered fiber lasers, achieving self-starting, broad-bandwidth, high-efficiency, and low-noise soliton microcombs at ≥ 10 GHz.

The catalyst pore structure is important to accommodate deposits in the hydrotreatment processes. In the current study, urchin alumina with large pore mouths was successfully synthesized by template free method, and was used as catalyst support for the hydrodesulfurization (HDS) of Siberian crude oil. Commercial alumina was used as reference. The catalysts were characterized by XRD, N 2 physisorption, TPR, NH 3 -TPD, SEM, and was evaluated in a trickle-bed reactor. The urchin alumina exhibits smaller surface area and larger average pore diameter than the commercial alumina. NiMo/ur-Al 2 O 3 shows similar activity and better stability within the long-term HDS run of 100 h. After the HDS test, the weight loss of coke over NiMo/ur-Al 2 O 3 is about half of that over NiMo/com-Al 2 O 3 ; however, the urchin morphology of NiMo/ur-Al 2 O 3 is not retained due to the high pressure during the reaction. The better performance in carbon resistance is consistent with the “chestnut bur” catalyst reported by IFP; this work supplements the synthesis detail and characterizations for the urchin-alumina supported catalyst, and provides important information for industrial hydrotreatment catalyst development. Graphic abstract

Background Gastric cancer (GC) is a leading cause of cancer deaths, and an increased number of GC patients adopt to next-generation sequencing (NGS) to identify tumor genomic alterations for precision medicine. Methods In this study, we established a hybridization capture-based NGS panel including 612 cancer-associated genes, and collected sequencing data of tumors and matched bloods from 153 gastric cancer patients. We performed comprehensive analysis of these sequencing and clinical data. Results 35 significantly mutated genes were identified such as TP53 , AKAP9 , DRD2 , PTEN , CDH1 , LRP2 et al. Among them, 29 genes were novel significantly mutated genes compared with TCGA study. TP53 is the top frequently mutated gene, and tends to mutate in male (p = 0.025) patients and patients whose tumor located in cardia (p = 0.011). High tumor mutation burden (TMB) gathered in TP53 wild-type tumors (p = 0.045). TMB was also significantly associated with DNA damage repair (DDR) genes genotype (p = 0.047), Lauren classification (p = 1.5e−5), differentiation (1.9e−7), and HER2 status (p = 0.023). 38.31% of gastric cancer patients harbored at least one actionable alteration according to OncoKB database. Conclusions We drew a comprehensive mutational landscape of 153 gastric tumors and demonstrated utility of target next-generation sequencing to guide clinical management.

Purpose There is no gold standard method to predict pathological complete response (pCR) in esophageal squamous cell carcinoma (ESCC) patients before surgery after neoadjuvant chemoradiotherapy (nCRT). This study aims to investigate whether dual layer detector dual energy CT (DECT) quantitative parameters and clinical features could predict pCR for ESCC patients after nCRT. Patients and methods This study retrospective recruited local advanced ESCC patients who underwent nCRT followed by surgical treatment from December 2019 to May 2023. According to pCR status (no visible cancer cells in primary cancer lesion and lymph nodes), patients were categorized into pCR group ( N  = 25) and non-pCR group ( N  = 28). DECT quantitative parameters were derived from conventional CT images, different monoenergetic (MonoE) images, virtual non-contrast (VNC) images, Z-effective (Zeff) images, iodine concentration (IC) images and electron density (ED) images. Slope of spectral curve (λHU), normalized iodine concentration (NIC), arterial enhancement fraction (AEF) and extracellular volume (ECV) were calculated. Difference tests and spearman correlation were used to select quantitative parameters for DECT model building. Multivariate logistic analysis was used to build clinical model, DECT model and combined model. Results A total of 53 patients with locally advanced ESCC were enrolled in this study who received nCRT combined with surgery and underwent DECT examination before treatment. After spearman correlation analysis and multivariate logistic analysis, AEF and ECV showed significant roles between pCR and non-pCR groups. These two quantitative parameters were selected for DECT model. Multivariate logistic analysis revealed that LMR and RBC were also independent predictors in clinical model. The combined model showed the highest sensitivity, specificity, PPV and NPV compared to the clinical and DECT model. The AUC of the combined model is 0.893 (95%CI: 0.802–0.983). Delong’s test revealed the combined model significantly different from clinical model (Z =-2.741, P  = 0.006). Conclusion Dual-layer DECT derived ECV fraction and AEF are valuable predictors for pCR in ESCC patients after nCRT. The model combined DECT quantitative parameters and clinical features might be used as a non-invasive tool for individualized treatment decision of those ESCC patients. This study validates the role of DECT in pCR assessment for ESCC and a large external cohort is warranted to ensure the robustness of the proposed DECT evaluation criteria.

Background Conventional single-energy CT can only provide a raw estimation of electron density (ED) for dose calculation by developing a calibration curve that simply maps the HU values to ED values through their correlations. Spectral CT, also known as dual-energy CT (DECT) or multi-energy CT, can generate a series of quantitative maps, such as ED maps. Using spectral CT for radiotherapy simulations can directly acquire ED information without developing specific calibration curves. The purpose of this study is to assess the feasibility of utilizing electron density (ED) maps generated by a novel dual-layer detector spectral CT simulator for dose calculation in radiotherapy treatment plans. Methods 30 patients from head&neck, chest, and pelvic treatment sites were selected retrospectively, and all of them underwent spectral CT simulation. Treatment plans based on conventional CT images were transplanted to ED maps with the same structure set, including planning target volume (PTV) and organs at risk (OARs), and the dose distributions were then recalculated. The differences in dose and volume histogram (DVH) parameters of the PTV and OARs between the two types of plans were analyzed and compared. Besides, gamma analysis between these plans was performed by using MEPHYSTO Navigator software. Results In terms of PTV, the homogeneity index (HI), gradient index (GI), D 2% , D 98% , and D mean showed no significant difference between conventional plans and ED plans. For OARs, statistically significant differences were observed in parotids D 50% , brainstem in head&neck plans, spinal cord in chest plans and rectum D 50% in pelvic plans, whereas the variance remained minor. For the rest, the DVH parameters exhibited no significant difference between conventional plans and ED plans. All of the mean gamma passing rates (GPRs) of gamma analysis were higher than 90%. Conclusion Compared to conventional treatment plans relying on CT images, plans utilizing ED maps demonstrated similar dosimetric quality. However, the latter approach enables direct utilization in dose calculation without the requirements of establishing and selecting a specific Hounsfield unit (HU) to ED calibration curve, providing an advantage in clinical applications.