Identification of ferroptosis-related subtypes, characteristics of TME infiltration and development of prognostic models in gastric cancer.

BACKGROUND: Ferroptosis is a distinct form of cell death characterized by unique morphology, biochemistry, and genetics, playing a crucial role in the initiation, progression, prognosis, and therapeutic strategies of tumors. However, the impact of ferroptosis-related genes (FRGs) on the tumor microenvironment (TME) remains unclear. This study may advance the existing knowledge of FRGs in gastric cancer, and push ahead with more effective prognostic assessment and the development of more effective immunotherapy approaches. METHODS: FRGs were acquired from the FerrDb database and a consensus clustering technique was adopted to categorize patients with GC into groups in line with the expression profiles of 44 FRGs in order to further investigate the expression properties of these proteins. Assessment of the immune status, microsatellite instability (MSI) and cancer stem cell (CSC) index between the high- and low- risk groups to assess the proportion of TIICs in the TME, ssGSVA was adopted to detect the abundance of infiltrating immune cells from the low-risk and high-risk groups. Expression levels of eight ferroptosis-related genes of prognostic signature in GC tissues and adjacent normal tissues was detected by RT-PCR. RESULTS: In the GC cohort, TP53 has the highest mutation frequency (44 %), and was shown to be highly linked with the expression levels of 11 FRGs. In accordance with the Kaplan-Meier curve, the overall survival time of patients with subtype A (Low FRG-score) discernibly exceeded that of patients with subtype B (High FRG-score).In addition, there is a significant difference in the infiltration of most immune cells between subtype A and subtype B, and some important immune checkpoints (CTLA4, PDCD1, CD274, LAG3, PDCD1LG2, and HAVCR2) have higher expression in cluster A. Finally, low FRG-scores were significantly associated with MSI-H status, while high FRG-scores were significantly associated with microsatellite stable status (MSS). FRG-score is negatively related to the cancer stem cell (CSC). CONCLUSION: Low FRG-score, due to its high microsatellite instability (MSI-H), high mutational load and immune activation, indicates the possible advantage of OS. In addition, the FRG-score was closely related to the cancer stem cell (CSC) index and the sensitive degree of chemotherapeutic drug.

Measurement of a Richtmyer-Meshkov Instability at an Air-SF_{6} Interface in a Semiannular Shock Tube.

We report the first measurements of the perturbation amplitude in the converging Richtmyer-Meshkov instability in a semiannular shock tube. At early stages, the amplitude growth agrees well with the impulsive model considering the geometrical convergence effect. A quick decrease of the growth rate at late time, even to be negative, before the reshock is observed for the first time. The reduction of the growth rate is ascribed to the Rayleigh-Taylor stabilization caused by the interface deceleration motion only presented in the converging circumstance. By reasonably evaluating the Rayleigh-Taylor stabilization, a modified model based on the Bell equation is proposed, which well predicts the perturbation growth in a converging geometry from early to late stages before the reshock. It is also found that the flow compressibility is significant in the converging Richtmyer-Meshkov instability.

Richtmyer-Meshkov instability of a flat interface subjected to a rippled shock wave.

The Richtmyer-Meshkov (RM) instability of a nominally flat interface (N_{2}/SF_{6}) subjected to a rippled shock, as the counterpart of a corrugated interface interacting with a planar shock, is studied experimentally in a vertical shock tube using both schlieren photography and fog visualization diagnostics. The nonplanar incident shock wave is produced by a planar shock diffracting around a rigid cylinder, and the flat interface is created by a membraneless technique. Three different distances η (the ratio of spacing from cylinder to interface over cylinder diameter) are considered. Schlieren images indicate that the nonplanar incident shock can be divided into three different segments separated by two triple points. Fog visualization pictures show the formation of overall "Λ" shaped interface structures and a N_{2} cavity at the center and two interface steps at both sides. With the increase of the dimensionless time, the dimensionless interface amplitude increases as well as the penetration depth of the cavity, and both curves exhibit reasonable collapse for different η numbers. Through equating the preinterface perturbation of the rippled shock with a preshock perturbation of a corrugated interface, the growth rate of this instability is found to be noticeably smaller than that of the standard RM instability.

Principal curvature effects on the early evolution of three-dimensional single-mode Richtmyer-Meshkov instabilities.

The Richtmyer-Meshkov instability (RMI) of single-mode air-SF(6) interfaces is studied numerically and the emphasis is placed on the effect of the principal curvature on the early evolution of the shocked interface. Two three-dimensional initial interfaces with opposite (3D-) and identical (3D+) principal curvatures and a traditional two-dimensional interface (2D) are considered. The weighted essentially nonoscillatory scheme and the Level-Set method combined with the real ghost fluid method are adopted. For comparison, perturbations on the initial interfaces with the same wavelength and amplitude in the symmetry plane are employed. The numerical results confirm the experimental finding that the growth rate of perturbations in the symmetry plane at the linear stage in the 3D- case is much smaller than that in the 2D and 3D+ cases. The difference among them can be ascribed to the different pressure and vorticity distributions associated with the principal curvatures of the initial interface. On the one hand, the high-pressure zones in the vicinity of the deformed interface are significantly different for three cases especially in the very beginning. The shock convergence and divergence at the interface are more severe in the 3D+ case than those in the 2D case, while the wave pattern in the 3D- case is more complex. On the other hand, the baroclinic vorticity distribution plays a leading role in the interface deformation of the 3D RMI after the passage of the planar shock. The accumulated vorticity changes the movement of the deformed interface and makes the local growth of perturbations different among three cases.

Richtmyer-Meshkov instability of a three-dimensional SF_{6}-air interface with a minimum-surface feature.

The Richmyer-Meshkov instability of a three-dimensional (3D) SF_{6}-air single-mode interface with a minimum-surface feature is investigated experimentally. The interface produced by the soap film technique is subjected to a planar shock and the evolution of the shocked interface is captured by time-resolved schlieren photography. Different from the light-heavy single-mode case, a phase inversion occurs in the shock-interface interaction and a bubblelike structure is observed behind the shocked interface, which may be ascribed to the difference in pressure perturbation at different planes. The superimposition of spikelike forward-moving jets forms a complex structure, indicating a distinctly 3D effect. Quantitatively, it is also found that the instability at the symmetry plane grows much slower than the prediction of two-dimensional linear model, but matches the extended 3D linear and nonlinear models accounting for the curvature effects. Therefore, the opposite curvatures of the 3D interface are beneficial for suppressing the growth of the instability.

A cylindrical converging shock tube for shock-interface studies.

A shock tube facility for generating a cylindrical converging shock wave is developed in this work. Based on the shock dynamics theory, a specific wall profile is designed for the test section of the shock tube to transfer a planar shock into a cylindrical one. The shock front in the converging part obtained from experiment presents a perfect circular shape, which proves the feasibility and reliability of the method. The time variations of the shock strength obtained from numerical simulation, experiment, and theoretical estimation show the desired converging effect in the shock tube test section. Particular emphasis is then placed on the problem of shock-interface interaction induced by cylindrical converging shock waves. For this purpose, membrane-less gas cylinder is adopted to form the interface between two different fluids while the laser sheet technique to visualize the flow field. The result shows that it is convenient to perform such experiments in this facility.

An HPLC-ESI-MS method for simultaneous determination of fourteen metabolites of promethazine and caffeine and its application to pharmacokinetic study of the combination therapy against motion sickness.

The combination therapy, promethazine and caffeine had been proven effective in treating motion sickness and counteracting some possible side effects of using promethazine alone while the mechanism and interaction remained unclear. Therefore, an HPLC-ESI-MS method for simultaneous determination of both drugs, and their metabolites was developed for purpose of pharmacokinetic study. To determine as many metabolites as possible, the influence of parameters such as column, flow rate and pH value of mobile phase, ionization polarity and fragmentation voltage were optimized. Fourteen target analytes were well separated and all of them could be identified and determined in plasma after administration of promethazine and caffeine. The LODs and LOQs were 0.9-6.0 and 2.50-16.0 ng/ml, respectively; the recoveries of three levels of quality control samples were from 86.7% to 102%; the intra-day and inter-day precisions were less than 3% and 9%, separately; and the RSDs of compound stability were all lower than 10% within 24h after sample preparation. As a pharmacokinetic study of the combination therapy in 30 healthy volunteers, concentration-time curves of the drugs and metabolites were studied. The present method for simultaneous measurement of more than ten metabolites is valuable for the study of mechanism and interaction of the combination therapy.