Objective: Ovarian cancer (OV) is the most fatal and frequent type of gynecological malignancy worldwide. TIMELESS (TIM), as a circadian clock gene, has been found to be highly expressed and predictive of poor prognosis in various cancers. However, the function of TIM in OV is not known. This study was designed to investigate the biological functions and underlying mechanisms of TIM during OV progression.Methods: Cell viability assay, cell migration assay, immunohistochemistry staining, qPCR analyses, and tumor xenograft model were used to identify the functions of TIM in OV. Bioinformatics analyses, including GEPIA, cBioPortal, GeneMANIA, and TIMER, were used to analyze the gene expression, genetic alteration, and immune cell infiltration of TIM in OV.Results: TIM is highly expressed in OV patients. TIM knockdown inhibited OV cell proliferation, migration, and invasion both in vitro and in vivo. Genetic alteration of TIM was identified in patients with OV. TIM co-expression network indicates that TIM had a wide effect on the immune cell infiltration and activation in OV. Further analysis and experimental verification revealed that TIM was positively correlated with macrophages infiltration in OV.Conclusions: Our study unveiled a novel function of highly expressed TIM associated with immune cell especially macrophages infiltration in OV. TIM may serve as a potential prognostic biomarker and immunotherapy target for OV patients.
Inner magnetospheric magnetosonic waves are usually considered to grow from the near‐equatorial ion Bernstein instability below the lower hybrid resonance frequency and contribute significantly to the radiation belt electron dynamics. We here present unusual observations of magnetosonic waves extending above the local lower hybrid resonance frequency in the midlatitude ∼15° plasmasphere after the substorm proton injection. Linear instability analyses and ray‐tracing simulations show that, because of the latitudinal variation of normal angles, these waves have little growth near the equator but are amplified accumulatively to the observable level over broad latitudes |λ| < 30° during the bounce‐drift propagation. Our data and modeling illustrate a previously unexplored scenario that off‐equatorial proton ring distributions could be a significant source of magnetosonic waves in the inner magnetosphere. Such off‐equatorially generated magnetosonic waves might differ from the near‐equatorially generated ones in latitudinal coverage, wavevector distribution, and then effect on the radiation belt electrons.
Whistler‐mode hiss waves play an important role in the radiation belt electron depletion. Whether the hiss waves with significant differences in amplitude and propagation direction within the plasmaspheric core and plume are related to each other remains unclear. We here show that the plasmaspheric plume facilitates the energy conversion from energetic electrons to hiss waves and then guides hiss waves into the plasmaspheric core. Three ground and space missions captured the initial formation and subsequent rotation of the plasmaspheric plume in the noon‐dusk‐midnight sector following a strong substorm. The observed hiss waves in the nightside plasmaspheric plume and core propagated oppositely but highly correlated with each other at a time lag of 4–10 s. The linear instability of energetic electrons in the plasmaspheric plume qualitatively explains the frequency‐dependence of hiss waves, and the ray‐tracing modeling reproduces the propagation direction and timing of hiss waves.
4 January 2024 in Journal of Geophysical Research: Space Physics
Purpose: Ovarian cancer (OC) is the leading cause of death from gynecological malignancies, and its etiology and pathogenesis are currently unclear. Recent studies have found that PUF60 overexpressed in various cancers. However, the exact function of PUF60 in global RNA processing and its role in OC has been unclear. Methods: The expression of PUF60 and its relationship with clinical characteristics were analyzed by multiple database analysis and immunohistochemistry. Phenotypic effects of PUF60 on ovarian cancer cell proliferation and metastasis were examined by in vitro cell proliferation assay, migration assay, and in vivo xenograft models and lung metastasis models. RNA immunoprecipitation, seahorse analyses, RNA stability assay were used to study the effect of PUF60 on the stability of oxidative phosphorylation (OXPHOS)-related genes in OC. Results: We report PUF60 is highly expressed in OC with frequent amplification of up to 33.9% and its upregulation predicts a poor prognosis. PUF60 promotes the proliferation and migration of OC cells both in vitro and in vivo. Mechanistically, we demonstrated that silencing of PUF60 enhanced the stability of mRNA transcripts involved in OXPHOS and decreased the formation of processing bodies (P-bodies), ultimately elevating the OXPHOS level. Conclusion: Our study unveils a novel function of PUF60 in OC energy metabolism. Thus, PUF60 may serve as a novel target for the treatment of patients with OC.
1 January 2021 in Annals of Translational Medicine
Background: The aim of this study was to determine the effects of different therapies on patients with cervical cancer (CC) with intermediate risk factors. Methods: Clinicopathological data of 596 patients diagnosed with stage I–IIA CC at the Obstetrics and Gynecology Hospital of Fudan University between January 2013 and November 2015 were retrospectively reviewed. Of the patients, 500 patients received adjuvant therapy including chemotherapy (CT), radiotherapy (RT), and sequential chemotherapy and radiotherapy (CT + RT). Patients who displayed at least one intermediate risk factor number were screened. Results: The median follow-up was 62 months. The 5-year progression-free survival (PFS) and overall survival (OS) of the entire cohort were 90.4% and 90.9%, respectively. Univariate analysis showed that tumor stage, tumor size, pathological type, lymphovascular space invasion, and numbers of medium risk factors were not risk factors for early-stage CC. Compared with the control group, patients who received CT, RT, or CT + RT showed improved PFS and OS (P<0.05). The RT group had lower PFS and OS than the CT and CT + RT groups (P<0.05). Among the 318 patients with a single intermediate risk factor, 297 patients received CT, RT, and CT + RT benefit from adjuvant therapy (P<0.05). Of the 253 patients with high-risk factors, 220 patients received CT, RT and CT + RT get improved PFS and OS (P<0.05). Conclusions: Patients who received adjuvant therapy had better postoperative outcomes than those who did not receive adjuvant therapy. Patients had CT alone or CT combined with RT had better efficacy than those had RT alone.