Activation of the DDR Pathway Leads to the Down-Regulation of the TGFβ Pathway and a Better Response to ICIs in Patients With Metastatic Urothelial Carcinoma

Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of metastatic urothelial carcinoma (mUC), a dominant type of bladder cancer (BC). Previous studies have shown an association between gene mutations in the DNA damage response (DDR) pathway and the immunotherapy response in mUC but have neglected the effect of the activation level of the DDR pathway on the ICI response in mUC. A published immunotherapy cohort with genome, transcriptome and survival data for 348 mUC patients was used. An external cohort (The Cancer Genome Atlas Bladder Cancer) and the GSE78220 cohort were used for validation. The activation level of the DDR pathway was quantified using single-sample gene set enrichment analysis (ssGSEA). Further analysis on the genome, immunogenicity, and the immune microenvironment was conducted using the DDR ssGSEA enrichment score-high (DSSH) group and the DDR ssGSEA enrichment score-low (DSSL) group. In the mUC cohorts, the DSSH group was associated with longer overall survival times (P=0.026; Hazard ratio=0.67; 95%CI: 0.46−0.95). The DSSH group was also associated with higher tumor mutation burden, neoantigen load, immune-activated cell patterns, and immune-related gene expression levels. The GSEA results indicated an immune activation state in DSSH group, which correlated with a down-regulation in the transforming growth factor β receptor signaling pathway. Our study suggests that the activation level of the DDR pathway may be a novel predictive marker for immunotherapy efficacy in patients with mUC

The dynamic evolution of multipoint interplanetary coronal mass ejections observed with BepiColombo, Tianwen-1, and MAVEN

We present two multipoint interplanetary coronal mass ejections (ICMEs) detected by the Tianwen-1 and Mars Atmosphere and Volatile Evolution spacecraft at Mars and the BepiColombo (0.56 au ∼0.67 au) upstream of Mars from 2021 December 5 to 31. This is the first time that BepiColombo is used as an upstream solar wind monitor ahead of Mars and that Tianwen-1 is used to investigate the magnetic field characteristics of ICMEs at Mars. The Heliospheric Upwind Extrapolation time model was used to connect the multiple in situ observations and the coronagraph observations from STEREO/SECCHI and SOHO/LASCO. The first fast coronal mass ejection event (∼761.2 km s−1), which erupted on December 4, impacted Mars centrally and grazed BepiColombo by its western flank. The ambient slow solar wind decelerated the west flank of the ICME, implying that the ICME event was significantly distorted by the solar wind structure. The second slow ICME event (∼390.7 km s−1) underwent an acceleration from its eruption to a distance within 0.69 au and then traveled with the constant velocity of the ambient solar wind. These findings highlight the importance of background solar wind in determining the interplanetary evolution and global morphology of ICMEs up to Mars distance. Observations from multiple locations are invaluable for space weather studies at Mars and merit more exploration in the future

Ground calibration of the Mars orbiter magnetometer onboard Tianwen-1

Ground calibration experiments of the Mars orbiter magnetometer (MOMAG) onboard the orbiter of Tianwen-1 were performed to determine the sensitivity, misalignment angle, and offset of the sensors. The linearity of the applied calibrated magnetic fields and the output from the sensors were confirmed to be better than 10−4, and the sensor axes were orthogonal to each other within 0.5 degrees. The temperature dependencies of the sensitivity and misalignment angle were examined, but no clear signatures of temperature dependencies could be seen. Sensor offset and the stability of sensor offset drift with a temperature change were also determined by the rotation method. The stability of the sensor offset drift was less than 0.01 nT/°C. The ground calibration of MOMAG determines all the calibration parameters of the sensors for accurate magnetic field measurements in orbit with the appropriate corrections

Martian Bow Shock Oscillations Driven by Solar Wind Variations: Simultaneous Observations From Tianwen‐1 and MAVEN

International audienceThe Martian bow shock stands as the first defense against the solar wind and shapes the Martian magnetosphere. Previous studies showed the correlation between the Martian bow shock location and solar wind parameters. Here we present direct evidence of solar wind effects on the Martian bow shock by analyzing Tianwen‐1 and MAVEN data. We examined three cases where Tianwen‐1 data show rapid oscillations of the bow shock, while MAVEN data record changes in solar wind plasma and magnetic field. The results indicate that the bow shock is rapidly compressed and then expanded during the dynamic pressure pulse in the solar wind, and is also oscillated during the IMF rotation. The superposition of variations in multiple solar wind parameters leads to more intensive bow shock oscillation. This study emphasizes the importance of joint observations by Tianwen‐1 and MAVEN for studying the real‐time response of the Martian magnetosphere to the solar wind

Interplanetary Coronal Mass Ejections and Stream Interaction Regions Observed by Tianwen-1 and MAVEN at Mars

The Tianwen-1 spacecraft is China's first Mars exploration mission. The Mars Orbiter Magnetometer (MOMAG) is a scientific instrument on board the Tianwen-1 mission that is designed to study magnetic fields at Mars, including the solar wind to the magnetosheath and the ionosphere. Using the first Tianwen-1/MOMAG data that is publicly available, we present an interplanetary coronal mass ejection (ICME) and stream interaction region (SIR) list based on in situ observations at Mars between 2021 November 16 and 2021 December 31. We compared the magnetic field intensity and vector magnetic field measurements from Tianwen-1/MOMAG and Mars Atmospheric Volatile EvolutioN (MAVEN)/Magnetometer (MAG) during the ICME and SIR interval and found a generally good consistency between them. Due to MAVEN's orbital adjustment since 2019, the Tianwen-1/MOMAG instrument is almost unique in its status as an interplanetary magnetic field monitor currently at Mars. The observations indicate that the MOMAG instrument on Tianwen-1 is performing well and can provide accurate measurements of the vector magnetic field in the near-Mars solar wind space. The multipoint observations combining MOMAG, MINPA, and MEPA on board Tianwen-1 with MAG, SWIA, and STATIC on board MAVEN will help develop systematic studies of the characteristics of ICMEs and SIRs at Mars, and their influences on the Martian atmosphere and ionosphere

Tianwen-1 and MAVEN observations of the response of Mars to an interplanetary coronal mass ejection

Interplanetary coronal mass ejections (ICMEs) are solar transients that have significant effects on the upper atmosphere and ionosphere of Mars. The simultaneous spacecraft observations from Tianwen1/MOMAG in solar wind and multiple instruments onboard the Mars Atmosphere and Volatile Evolution (MAVEN) in the Martian upper atmosphere are used to study the response of Mars to an ICME. The ICME was observed at Mars by Tianwen-1 and MAVEN at 00:00 UT on 10 December, 2021, which was earlier observed by BepiColombo upstream of Mars at 22:32 UT on 6 December, 2021. During 6–15 December 2021, MAVEN measured the nightside ionosphere and Tianwen-1 measured the dayside ionosphere while both were inside the Martian bow shock. The rapid drop in densities of ionospheric ions and electrons, which is typically identified as the end of the ionosphere at altitudes between 300 and 800 km, is known as ionopause. The altitude of the Martian ionopause location was lowered by the high dynamic pressure of solar wind during the ICME passage. The depletion of the plasma density in the topside Martian ionosphere on the nightside reveals the presence of substantial ion and electron escape to space through the interaction between the ICME and Mars. The column abundance of plasma dramatically decreased, with 34% e−, 61% O+2, and 73% O+ 36 reduced. This study highlights the significant impact of the space weather associated with the intense magnetic field and high dynamic pressure of the ICME on Mars’ atmosphere, which is particularly important for future human exploration missions to Mars