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The epithelial-mesenchymal transition (EMT) is crucial to cancer progression and metastasis. Although multiple cellular miRNAs have been identified to regulate the EMT and metastasis in cancers, the role of viral miRNAs in cancer progression remains largely unknown. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy typically characterized by its early metastasis. In the present study, we have discovered the involvement of a viral miRNA, EBV-miR-BART7-3p, in the EMT and metastasis of NPC cells. Initially, we observed that EBV-miR-BART7-3p was highly expressed in NPC and positively correlated with lymph node metastasis and clinical stage of NPC. Subsequently, we demonstrated that EBV-miR-BART7-3p enhanced cell migration/invasion in vitro , cancer metastasis in vivo , and particularly the EMT characterized by loss of epithelial markers and gain of mesenchymal features in NPC cells. Furthermore, mechanistic studies disclosed that EBV-miR-BART7-3p targeted a major human tumor suppressor PTEN, modulating PI3K/Akt/GSK-3β signaling and eventually leading to the high expression and nuclear accumulation of Snail and β-catenin, which favor EMT. Knockdown of PTEN could phenocopy the effect of EBV-miR-BART7-3p, whereas re-expression of PTEN resulted in a phenotypic reversion. Moreover, these findings were supported by an observation of an EBV-positive cell model in which silencing of endogenous EBV-miR-BART7-3p partially attenuated cell migration/invasion and altered EMT protein expression pattern via reverting PI3K/Akt, Snail and β-catenin expression. Thus, this study suggests a novel mechanism by which EBV-miR-BART7-3p modulates the EMT and metastasis of NPC cells, and a clinical implication of EBV-miR-BART7-3p as a potential biomarker or therapeutic target.

Gamma-ray bursts (GRBs) have been phenomenologically classified into long and short populations based on the observed bimodal distribution of duration 1 . Multi-wavelength and multi-messenger observations in recent years have revealed that in general long GRBs originate from massive star core collapse events 2 , whereas short GRBs originate from binary neutron star mergers 3 . It has been known that the duration criterion is sometimes unreliable, and multi-wavelength criteria are needed to identify the physical origin of a particular GRB 4 . Some apparently long GRBs have been suggested to have a neutron star merger origin 5 , whereas some apparently short GRBs have been attributed to genuinely long GRBs 6 whose short, bright emission is slightly above the detector’s sensitivity threshold. Here, we report the comprehensive analysis of the multi-wavelength data of the short, bright GRB 200826A. Characterized by a sharp pulse, this burst shows a duration of 1 second and no evidence of an underlying longer-duration event. Its other observational properties such as its spectral behaviours, total energy and host galaxy offset are, however, inconsistent with those of other short GRBs believed to originate from binary neutron star mergers. Rather, these properties resemble those of long GRBs. This burst confirms the existence of short-duration GRBs with stellar core-collapse origin 4 , and presents some challenges to the existing models. A gamma-ray burst (GRB) is reported to show a sharp 1-second spike, characteristic of short GRBs, but with other observational properties resembling those of long GRBs. This burst may belong to a class of core-collapse-origin GRBs with genuinely short durations.

The symmetry of Cooper pairs in iron-based superconductors is an issue under continued investigation. A scanning tunnelling study of Fe(Te,Se) reveals a robust zero-energy bound state, providing evidence for a non-trivial pairing symmetry. In superconductors, electrons are paired and condensed into the ground state. An impurity can break the electron pairs into quasiparticles with energy states inside the superconducting gap. The characteristics of such in-gap states reflect accordingly the properties of the superconducting ground state 1 . A zero-energy in-gap state is particularly noteworthy, because it can be the consequence of non-trivial pairing symmetry 1 or topology 2 , 3 . Here we use scanning tunnelling microscopy/spectroscopy to demonstrate that an isotropic zero-energy bound state with a decay length of ∼10 Å emerges at each interstitial iron impurity in superconducting Fe(Te,Se). More noticeably, this zero-energy bound state is robust against a magnetic field up to 8 T, as well as perturbations by neighbouring impurities. Such a spectroscopic feature has no natural explanation in terms of impurity states in superconductors with s -wave symmetry, but bears all the characteristics of the Majorana bound state proposed for topological superconductors 2 , 3 , indicating that the superconducting state and the scattering mechanism of the interstitial iron impurities in Fe(Te,Se) are highly unconventional.

Saturn’s magnetosphere, shaped by solar wind interaction with its dipole field, differs from Earth’s due to faster rotation and Enceladus’s internal plasma sources. An ongoing focus of investigation is how the internal plasma sources and rapid rotation result in a different global magnetospheric configuration. The magnetospheric cusp, a crucial interaction region between solar wind and planetary magnetic field, serves as an indicator of global magnetic configuration. Here we utilize Cassini observations from 2004 to 2010 to study dawn-dusk asymmetry in Saturn’s cusp distribution and extend the number of cusp events from about 11 reported in previous studies to 67. We find peak occurrence in the post-noon sector and signatures extending to post-dusk (near 20 local time), resembling recent observations of Jupiter’s post-dusk cusp. We further examine magnetic topology using high-resolution magnetohydrodynamic simulations to visualize the cusp asymmetry. This is consistent with previous studies, but our simulations provide a more detailed view of Saturn’s magnetic topology near the magnetopause. This asymmetry of cusp distribution demonstrates how rapid rotation and internal plasma sources fundamentally alter magnetospheric configuration, offering insights for understanding other rotating planetary systems within and beyond the solar system. The magnetospheric cusp is a key solar wind– magnetic field interface. Here, the authors show that Saturn’s cusp has a pronounced dawn–dusk asymmetry, with signatures reaching the postdusk region, unlike Earth’s near-noon cusp.

The upper reaches of most planetary atmospheres contain a layer that is ionized by incoming solar radiation—the ionosphere. As it went through its final orbits around Saturn, the Cassini spacecraft dipped close enough to the planet to pass directly through the ionosphere. Wahlund et al. examined the plasma data collected in situ and found that Saturn's ionosphere is highly variable and interacts with the planet's inner ring. They also observed decreases in ionization within regions shaded from the Sun by the rings. Science , this issue p. 66 The Cassini spacecraft has flown through Saturn’s ionosphere, which is highly variable and affected by the planet’s rings. The ionized upper layer of Saturn’s atmosphere, its ionosphere, provides a closure of currents mediated by the magnetic field to other electrically charged regions (for example, rings) and hosts ion-molecule chemistry. In 2017, the Cassini spacecraft passed inside the planet’s rings, allowing in situ measurements of the ionosphere. The Radio and Plasma Wave Science instrument detected a cold, dense, and dynamic ionosphere at Saturn that interacts with the rings. Plasma densities reached up to 1000 cubic centimeters, and electron temperatures were below 1160 kelvin near closest approach. The density varied between orbits by up to two orders of magnitude. Saturn’s A- and B-rings cast a shadow on the planet that reduced ionization in the upper atmosphere, causing a north-south asymmetry.

The accumulation of myeloid-derived suppressor cells (MDSCs) has been observed in solid tumors and is correlated with tumor progression; however, the underlying mechanism is still poorly understood. In this study, we identified a mechanism by which tumor cells induce MDSC accumulation and expansion in the bladder cancer (BC) microenvironment via CXCL2/MIF-CXCR2 signaling. Elevated expression of CXCL2 and MIF and an increased number of CD33 + MDSCs were detected in BC tissues, and these increases were significantly associated with advanced disease stage and poor patient prognosis ( P <0.01). A positive association was observed between CXCL2 or MIF expression and the number of tumor-infiltrating CD33 + MDSCs ( P <0.01). Subsequently, we demonstrated that CD45 + CD33 + CD11b + HLA-DR − MDSCs from fresh BC tissues displayed high levels of suppressive molecules, including Arg1, iNOS, ROS, PDL-1 and P-STAT3, and stronger suppression of T-cell proliferation. Interestingly, these CD45 + CD33 + CD11b + HLA-DR − MDSCs exhibited increased CXCR2 expression compared with that in peripheral blood from BC patients or healthy controls ( P <0.05). Chemotaxis assay revealed that bladder cancer cell line J82 induced MDSC migration via CXCL2/MIF-CXCR2 signaling in vitro . Mechanistic studies demonstrated that J82-induced MDSC trafficking and CXCR2 expression were associated with increased phosphorylation of p38, ERK and p65. Conversely, inhibition of the phosphorylation of p38, ERK or p65 decreased J82-induced MDSC trafficking and CXCR2 expression. CXCL2/MIF-stimulated activation of the mitogen-activated protein kinase and nuclear factor kappa B pathways in MDSCs was MyD88 dependent. Overall, our results identify the CXCL2/MIF-CXCR2 axis as an important mediator in MDSC recruitment and as predictors and potential therapeutic targets in BC patients.

Conflicting reports have emerged for rates of preterm births and stillbirths during the COVID-19 pandemic. Most of these reports did not account for natural variation in these rates. We aimed to evaluate variations in preterm birth and stillbirth rates before and during the COVID-19 pandemic in Ontario, Canada. We conducted a retrospective cohort study using linked population health administrative databases of pregnant people giving birth in any hospital in Ontario between July 2002 and December 2020. We calculated preterm birth and stillbirth rates. We assessed preterm birth at 22–28, 29–32 and 33–36 weeks’ gestation, and stillbirths at term and preterm gestation. We used Laney control P′ charts for the 18-year study period (6-mo observation periods) and interrupted time-series analyses for monthly rates for the most recent 4 years. We evaluated 2 465 387 pregnancies, including 13 781 that resulted in stillbirth. The mean preterm birth rate for our cohort was 7.96% (range 7.32%–8.59%). From January to December 2020, we determined that the preterm birth rate in Ontario was 7.87%, with no special cause variation. The mean stillbirth rate for the cohort was 0.56% (range 0.48%–0.70%). From January to December 2020, the stillbirth rate was 0.53%, with no special cause variation. We did not find any special cause variation for preterm birth or stillbirth subgroups. We found no changes in slope or gap between prepandemic and pandemic periods using interrupted time-series analyses. In Ontario, Canada, we found no special cause variation (unusual change) in preterm birth or stillbirth rates, overall or by subgroups, during the first 12 months of the COVID-19 pandemic compared with the previous 17.5 years.

“Hot papers” (HPs) are papers which received a boost of citations shortly after publication. Papers with “delayed recognition” (DRs) received scarcely impact over a long time period, before a considerable citation boost started. DRs have attracted a lot of attention in scientometrics and beyond. Based on a comprehensive dataset with more than 5,000,000 papers published between 1980 and 1990, we identified HPs and DRs. In contrast to many other studies on DRs, which are based on raw citation counts, we calculated dynamically field-normalized impact scores for the search of HPs and DRs. This study is intended to investigate the differences between HPs (n = 323) and DRs (n = 315). The investigation of the journals which have published HPs and DRs revealed that some journals (e.g. Physical Review Letters and PNAS) were able to publish significantly more HPs than other journals. This pattern did not appear in DRs. Many HPs and DRs have been published by authors from the USA; however, in contrast to other countries, authors from the USA have published statistically significantly more HPs than DRs. Whereas “Biochemistry & Molecular Biology,” “Immunology,” and “Cell Biology” have published significantly more HPs than DRs, the opposite result arrived for “Surgery” and “Orthopedics.” The results of the analysis of certain properties of HPs and DRs (e.g. number of pages) suggest that the emergence of DRs is an unpredictable process.

Metastasis is the major cause of death in colorectal cancer (CRC). Although multiple genes have been identified to be responsible for the development of CRC, the molecular changes that enable CRC cells to undergo early local invasion and to form distant metastatic colonies still remain largely unknown. Herein, we investigated the role of Forkhead box protein C2 (FOXC2) and explored the underlying mechanisms in invasion and metastasis of CRC. We show that both high FOXC2 expression and nuclear localization of FOXC2 are significantly correlated with advanced TNM (T=primary tumor; N=regional lymph nodes; M=distant metastasis) stages. FOXC2 enhanced the invasive abilities of CRC cells in vitro and promoted local invasion and distant metastasis in an orthotopic mouse metastatic model of CRC. Microarray analysis revealed that overexpression of FOXC2 increased the proto-oncogene MET tyrosine kinase expression and activated the hepatocyte growth factor (HGF)-MET signaling pathway. Furthermore, luciferase reporter assays and chromatin immunoprecipitation assays revealed that FOXC2 directly associated with MET promoter to increase the transcriptional activity of MET. Inhibition of MET attenuates the invasive phenotype and metastatic potential of FOXC2-overexpressing CRC cells, indicating that MET is a major mediator of FOXC2-promoted metastasis. In addition, FOXC2 expression was positively correlated with MET expression in CRC tissue samples. Our findings suggest that FOXC2 has a crucial role in CRC metastasis by regulating HGF-MET signaling via inducing MET expression, highlighting FOXC2 as a potential therapeutic target for preventing or reducing metastasis in CRC.

Since the advent in 2004, high-entropy alloys (HEAs) have been attracting a great deal of research interest worldwide. Being deemed as a major paradigmatic shift, the design of HEAs without base elements poses challenges to the existing thermodynamic models and theories that were long established for traditional alloys, one of which is related to the thermodynamic mechanisms for the formation of random solid solution in a concentrated multicomponent alloy. In this article, we discuss the design of HEAs from the perspective of correlated mixing (nonideal mixing of atoms with interatomic correlations). In a quantitative manner, we can show that the formation of a random solid solution in HEAs depends not only on the number of constituent elements but also on the alloy’s melting/processing temperature and on various interatomic correlations. Through the correlated mixing rule, we further demonstrate a strategy to screen out equiatomic alloys with the thermodynamic characteristics close to those of random solid solutions from an expanded library of 20 candidate elements.