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In this study, the relationship between AO and winter synoptic temperature variability (STV) over the Northern Hemisphere is examined in 34 CMIP5/CMIP6 model outputs. With significant model bias around the North Pacific and North Atlantic, most models fail to capture the correct AO–STV pattern in historical simulations compared to observations. To investigate the bias of AO–STV relationship simulations, AO-related processes for the connection between AO and winter STV are examined in high pattern score (HPS) models and low pattern score (LPS) models, respectively. Furthermore, the bias of AO impact can be traced back to AO pattern simulations. On the one hand, compared to observations, HPS models can overall capture the intensity in the North Pacific and North Atlantic center of AO. On the other hand, LPS models tend to overestimate the North Pacific center and underestimate the North Atlantic center. In addition, similar to historical simulations, a robust AO–STV relationship can still be found over the Northern Hemisphere in future projections based on HPS models. Meanwhile, the uncertainty of the projected AO–STV relationship in the multimodel ensemble is confined mainly to the North Pacific, consistent with the large diversity of intensity over the North Pacific center of AO, which is related to the uncertainty of the relationship between AO and regional mode variability.

Immunotherapies targeting the PD-1/PD-L1 axis have become first-line treatments in multiple cancers. However, only a limited subset of individuals achieves durable benefits because of the elusive mechanisms regulating PD-1/PD-L1. Here, we report that in cells exposed to interferon-γ (IFNγ), KAT8 undergoes phase separation with induced IRF1 and forms biomolecular condensates to upregulate PD-L1. Multivalency from both the specific and promiscuous interactions between IRF1 and KAT8 is required for condensate formation. KAT8–IRF1 condensation promotes IRF1 K78 acetylation and binding to the CD247 (PD-L1) promoter and further enriches the transcription apparatus to promote transcription of PD-L1 mRNA. Based on the mechanism of KAT8–IRF1 condensate formation, we identified the 2142–R8 blocking peptide, which disrupts KAT8–IRF1 condensate formation and consequently inhibits PD-L1 expression and enhances antitumor immunity in vitro and in vivo. Our findings reveal a key role of KAT8–IRF1 condensates in PD-L1 regulation and provide a competitive peptide to enhance antitumor immune responses.

The North Atlantic Oscillation (NAO) generally has an in-phase relationship with surface air temperature (SAT) anomalies over Northeast China in late winter. The present study shows that such an NAO–SAT relationship becomes stronger during easterly phases of the quasi-biennial oscillation (QBO), but is relatively weak during westerly phases. Observational evidence reveals that the modulation effect of the QBO on the NAO–SAT relationship over Northeast China is attributable to QBO-induced changes in the spatial structure of the NAO and associated stratosphere–troposphere coupling. During easterly QBO phases, the NAO has a strong connection with the Northern Hemisphere stratospheric polar vortex, facilitating a hemisphere-wide structure of the NAO and thus a downstream extension of NAO signal from the Euro–Atlantic sector toward Northeast Asia. During westerly QBO phases, however, the NAO has a limited connection with the stratospheric polar vortex. In this case, the NAO features a classically regional mode, with the signal in the SAT field mainly confined to the Euro-Atlantic sector. By examining historical simulations from six climate models participating in CMIP6 and including stratospheric processes, it is found that none of these models captures a significant difference in the spatial structure of the NAO and its connection with the stratospheric polar vortex between the easterly and westerly QBO phases in late winter. A key reason may be related to the poor performance of the models in simulating the Holton–Tan effect, which is critical for linking the QBO and NAO. Significance Statement The QBO is the dominant mode of equatorial stratospheric variability and important for seasonal forecasting. This study aims to better understand the surface influence of the QBO by examining the relationship between the NAO and temperature anomalies over China according to the phases of the QBO during boreal winter. Our results highlight the importance of the QBO in modulating the spatial structure and thus climate impact of the NAO via stratosphere–troposphere coupling in observations, while state-of-the-art climate models perform poorly in simulating the QBO-related stratosphere–troposphere coupling and thus the QBO–NAO connection. These findings have important implications for seasonal prediction and model development in the future.

STING, an endoplasmic reticulum (ER) transmembrane protein, mediates innate immune activation upon cGAMP stimulation and is degraded through autophagy. Here, we report that activated STING could be transferred between cells to promote antitumor immunity, a process triggered by RAB22A-mediated non-canonical autophagy. Mechanistically, RAB22A engages PI4K2A to generate PI4P that recruits the Atg12–Atg5–Atg16L1 complex, inducing the formation of ER-derived RAB22A-mediated non-canonical autophagosome, in which STING activated by agonists or chemoradiotherapy is packaged. This RAB22A-induced autophagosome fuses with RAB22A-positive early endosome, generating a new organelle that we name Rafeesome (RAB22A-mediated non-canonical autophagosome fused with early endosome). Meanwhile, RAB22A inactivates RAB7 to suppress the fusion of Rafeesome with lysosome, thereby enabling the secretion of the inner vesicle of the autophagosome bearing activated STING as a new type of extracellular vesicle that we define as R-EV (RAB22A-induced extracellular vesicle). Activated STING-containing R-EVs induce IFNβ release from recipient cells to the tumor microenvironment, promoting antitumor immunity. Consistently, RAB22A enhances the antitumor effect of the STING agonist diABZI in mice, and a high RAB22A level predicts good survival in nasopharyngeal cancer patients treated with chemoradiotherapy. Our findings reveal that Rafeesome regulates the intercellular transfer of activated STING to trigger and spread antitumor immunity, and that the inner vesicle of non-canonical autophagosome originated from ER is secreted as R-EV, providing a new perspective for understanding the intercellular communication of organelle membrane proteins.

Southern China has experienced a discernible early-spring drying trend in recent decades. This drying trend is a direct result of a severe deficiency of water vapor, which is induced by local descent anomalies and strong anomalous northerlies from the northwestern Pacific. The predominant anomalous northerlies are directly associated with two anomalous warm highs over the North Pacific (NPH) and East Asia (EAH), respectively. Anomalous easterlies along the southern edge of the NPH divert southwestward over southern Japan and form a branch of the northerlies, which merges into strong northerlies east of the EAH to construct the prevalent and deep northerly anomalies along the coast of East Asia. The NPH is related to changes in the zonal contrast of the Pacific sea surface temperature (SST-Tri), whose linear trend is dominated by warming in the western Pacific. The change in SST-Tri causes more precipitation in the tropical North Pacific, where strong ascent occurs and further facilitates robust descent over the extratropical North Pacific, facilitating the formation of the NPH. The EAH results from the interaction of tropical and higher latitudinal forcing in the context of global warming. On the one hand, enhanced precipitation over the Maritime Continent associated with the change in SST-Tri induces descent anomalies of the EAH over southern China via a local Hadley cell circulation. On the other hand, a “positive–negative–positive” tripolar tendency over the North Atlantic forces a wave train, which propagates eastward, becomes intensified over the Ural Mountains, and then moves farther eastward to affect the EAH. In addition, changes in SST-Tri can also modulate the tripole pattern over the North Pacific to further contribute to the EAH.

Droughts and associated near-surface temperature anomalies can be attributed to amplified vertical subsidence and anomalous anticyclonic circulations from dynamic perspectives. However, two open and interesting issues remain unknown: 1) whether hydrometeorological situations under droughts can be reproduced directly utilizing variability of atmospheric dynamics and 2) what specific roles atmospheric dynamics play in drought reconstruction. To explore these questions, this study employs three kinds of dynamic features (i.e., vertical velocity, relative vorticity, and horizontal divergence) for hydrometeorological reconstruction (e.g., precipitation and near-surface air temperature) under drought situations through a so-called XGBoost (extreme gradient boosting) ensemble learning method. The study adopts two different reconstruction schemes (i.e., statistically preexisting dynamic–hydrometeorological relationships and interannual variability) and finds dynamically based reconstruction feasible. The three main achievements are as follows. 1) Regarding different hydrometeorological situations reconstructed with preexisting dynamic–hydrometeorological relationships, good reconstruction performance can be captured with the same or different lead times, depending on whether the evolution of dynamic anomalies (e.g., vertical motion and relative vorticity) is temporally asynchronous. 2) Reconstruction on the interannual scale performs relatively well, seemingly regardless of seasonality and drought-inducing mechanisms. 3) More importantly, from interpretable perspectives, global-scale analysis of dynamic contributions helps discover unexpected dynamic drought-inducing roles and associated latitudinal modulation. That is, low-level cyclonic/anticyclonic anomalies contribute to drought development in the northern middle and high latitudes, while upper-level vertical subsidence contributes significantly to tropical near-surface temperature anomalies concurrent with droughts. These achievements could provide guidance for dynamically based drought monitoring and prediction in different geographic regions. Significance Statement It is common sense that severe drought events are physically attributable to amplified vertical subsidence and anomalous anticyclonic circulations. However, the specific contributions of atmospheric dynamics, together with the feasibility of dynamically based drought reconstruction, are crucial components that are seldom investigated. To our knowledge, this manuscript is the first to reconstruct drought utilizing atmospheric dynamics and to interpret quantified dynamic contributions; it also represents a new interdisciplinary attempt to reproduce hydrological variability based on routine atmospheric dynamic variables.

The impact of El Niño–Southern Oscillation (ENSO) on the winter stratospheric polar vortex intensity (PVI) is re-examined, using JRA-55 datasets and the CESM2 model. Our results show that the negative correlation between ENSO and PVI has weakened in recent decades and is no longer statistically significant after the mid-1990s. This weakening ENSO–PVI relationship after the mid-1990s is associated with wave-1 fluxes entering the stratosphere; that is, the ENSO-induced increasing wave-1 fluxes are weaker after the mid-1990s than before the mid-1990s. Except for the Pacific–North America (PNA)-like wave train, the stratospheric wave flux changes are related to ENSO-induced geopotential height changes over East Asia. The ENSO-induced tropical zonal circulation anomalies are enhanced from the central Pacific to East Asia, leading to more substantial wave flux anomalies propagating westward from the central Pacific to East Asia and a more significant high center over Northeast Asia after the mid-1990s than before the mid-1990s. This ENSO-induced high center after the mid-1990s is out of phase with the climatological center of wave 1, leading to a relatively weaker increase in wave 1. Model results show that changes in the ENSO–PVI relationship and ENSO–Asia circulation are associated with changes in ENSO-related SST combined with global mean SST. Significance Statement In this study, changes in the ENSO–polar vortex relationship and the relevant mechanisms are analyzed from the perspective of the ENSO-induced East Asia circulation. The results can help us better understand and predict variations in the stratospheric polar vortex.

Transcription dysregulation is a salient characteristic of bladder cancer (BC), but no appropriate therapeutic target for it has been established. Here, we found that heterogeneous downregulation of histone H4 transcription factor (HINFP) was associated with senescence in BC tissues and that lower HINFP expression could predict an unfavorable outcome in BC patients. Knockout of HINFP transcriptionally inhibited H1F0 and H1FX to trigger DNA damage, consequently inducing cell senescence to repress the proliferation and growth of BC cells. However, the senescence-associated secretory phenotype, characterized by increases in MMP1/3, enhances the invasion and metastasis of non-senescent BC cells. Histone deacetylase inhibitors (HDACis) could efficiently eliminate the senescent cells induced by HINFP knockout to suppress the invasion and metastasis of BC cells. Our study suggests that HDACis, widely used in multiple cancer types in a clinical context, may also benefit BC patients with metastases induced by cell senescence.

Supplemental Figure S1. The over-expression of CBX4, but not of other CBX members, suppresses the migration of DLD1 cells. Supplementary Figure S2. The knockdown of CBX4 enhances migration and invasion of CRC cells. Supplementary Figure S3. The over-expression of CBX4 inhibits the cell migration and invasion of CRC cells. Supplementary Figure S4. CBX4 represses the liver metastasis of HCT116 cells. Supplementary Figure S5. CBX4 is negatively related to the Runx2 expression in CRC cell lines. Supplementary Figure S6. The knockdown of Runx2 decreases the expression of Slug. Supplementary Figure S7. The promotion of cell migration and invasion after CBX4 knockdown primarily depends on Runx2. Supplementary Figure S8. The knockdown of Slug also reverses the promotion of cell migration and invasion after CBX4 knockdown. Supplementary Figure S9. IHC antibodies specifically recognized CBX4 or Runx2 protein. Supplementary Figure S10. The ΔSIM1/2 and CDM mutations marginally affect the functions of CBX4 in CRC. Supplementary Figure S11. CBX4 strongly binds with HDAC1, HDAC2, HDAC3 and HDAC9. Supplementary Figure S12. HDAC1, HDAC2, and HDAC3, but not HDAC9, are expressed in the tested CRC cell lines. Supplementary Figure S13. The ΔSIM1/2 and CDM mutations marginally affect the interaction of CBX4 with HDAC3. Supplementary Figure S14. The binding affinity of HDAC3 with the Runx2 promoter was dependent on CBX4. Supplementary Figure S15. The knockdown of HDAC3 abrogates the functions of CBX4 in CRC. Supplementary Figure S16. Determination of CBX4 fragments interacting with HDAC3. Supplementary Figure S17. The C-terminal 10 amino acids of CBX4 are responsible for its interaction with Bmi1. Supplementary Figure S18. The ΔDM1-CBX4 and ΔTM-CBX4 mutations, but not the deltaC-CBX4 mutation, abolish the inhibition of cell migration and invasion by CBX4.

The transcriptome analysis of HCT116 cells transfected with scrambled or CBX4 shRNA.

Table S1 is the correlation between CBX4 expression and Runx2 expression of CRC patients, Table S2 is correlation between CBX4 expression and clinicopathologic characteristics of CRC patients, and Table S3 is univariate and multivariate analysis for overall survival.

Polycomb chromobox (CBX) proteins participate in the polycomb repressive complex (PRC1) that mediates epigenetic gene silencing and endows PRC1 with distinct oncogenic or tumor suppressor functions in a cell-type–dependent manner. In this study, we report that inhibition of cell migration, invasion, and metastasis in colorectal carcinoma requires CBX4-mediated repression of Runx2, a key transcription factor that promotes colorectal carcinoma metastasis. CBX4 inversely correlated with Runx2 expression in colorectal carcinoma tissues, and the combination of high CBX4 expression and low Runx2 expression significantly correlated with overall survival, more so than either CBX4 or Runx2 expression alone. Mechanistically, CBX4 maintained recruited histone deacetylase 3 (HDAC3) to the Runx2 promoter, which maintained a deacetylated histone H3K27 state to suppress Runx2 expression. This function of CBX4 was dependent on its interaction with HDAC3, but not on its SUMO E3 ligase, its chromodomain, or the PRC1 complex. Disrupting the CBX4–HDAC3 interaction abolished Runx2 inhibition as well as the inhibition of cell migration and invasion. Collectively, our data show that CBX4 may act as a tumor suppressor in colorectal carcinoma, and strategies that stabilize the interaction of CBX4 with HDAC3 may benefit the colorectal carcinoma patients with metastases. Cancer Res; 76(24); 7277–89. ©2016 AACR.

Addtional information on shRNA sequences, qRT-PCR primers, promoter cloning primers, antibodies and ChIP-qPCR primers used in this study.

Cu foams with 75% and 98% porosity were employed as reinforcing structures to enhance the performance of the Sn3.0Ag0.5Cu(SAC305)/Cu solder joints. The effects of Cu foam porosity and ultrasonic power on the microstructure and shear properties of solder joints were investigated. The results suggested that the Cu substrate produced excellent metallurgical reactions with both composite solder foils, but more Cu6Sn5 was generated in 75% porosity Cu foam/SAC305 solder joints. The increase of ultrasonic power would accelerate the dissolution of Cu skeleton and effectively refine and homogenize the intermetallic compound grains. Higher power ultrasonic vibration optimized the microstructure of the solder joint, so the shear strength of the joint was increased, but excessive ultrasonic power would cause microcracks at the interface of the solder joint in turn reducing the shear strength.

Tamarix chinensis Lour. is a shrub or 3-6-meter-tall small tree with high salt- and alkali- tolerance and aggressive invasiveness, mainly distributed in the eastern part of China in warm-temperate and subtropical climate zones. Molecular evidence indicated it expanded eastward from the western part of China quite recently in late Pleistocene about 0.02 Ma. With highly polymorphic microsatellites markers, we evaluated genetic structure and adaptation of nine T. chinensis populations mainly distributed in two estuarine flats of two climate zones: Yellow River Delta of warm-temperate and Hangzhou Bay of the subtropical zone. Despite a low population differentiation of FST= 0.0518, Bayesian clustering analysis, Discriminant Analysis of Principal Components (DAPC) and the unweighted pair group method with arithmetic mean (UPGMA) clearly identified three genetic clusters correlated to the populations’ geographic origin. Isolation by distance (IBD) and isolation by environment (IBE) patterns were detected at significant levels. A series of redundancy analyses (RDA) revealed significant contributions of geographical and environmental factors to genetic variation measured with environmental factors explaining a larger variance. The FST-based test (BayeScan) determined 5 out of 8 SSRs as outlier loci possibly at balancing selection. Further landscape genetic analysis identified some alleles significantly correlated to environmental variables including maximum temperature of the warmest month, minimum temperature of coldest month, and isothermality, signaling the adaptation of T. chinensis to temperature in two climate zones. Our result showed rapid evolution happened at a small temporal scale in a woody species with short generation time.

Rab22a-NeoF fusion protein has recently been reported as a promising target for osteosarcoma lung metastasis. However, how this fusion protein is regulated in cells remains unknown. Here, using multiple screenings, it is reported that Rab22a-NeoF1 fusion protein is degraded by an E3 ligase STUB1 via the autophagy receptor NDP52-mediated lysosome pathway, which is facilitated by PINK1 kinase. Mechanistically, STUB1 catalyzes the K63-linked ubiquitin chains on lysine112 of Rab22a-NeoF1, which is responsible for the binding of Rab22a-NeoF1 to NDP52, resulting in lysosomal degradation of Rab22a-NeoF1. PINK1 is able to phosphorylate Rab22a-NeoF1 at serine120, which promotes ubiquitination and degradation of Rab22a-NeoF1. Consistently, by upregulating PINK1, Sorafenib and Regorafenib can inhibit osteosarcoma lung metastasis induced by Rab22a-NeoF1. These findings reveal that the lysosomal degradation of Rab22a-NeoF1 fusion protein is targetable for osteosarcoma lung metastasis, proposing that Sorafenib and Regorafenib may benefit cancer patients who are positive for the RAB22A-NeoF1 fusion gene.

Using observation, reanalysis and model datasets, the impact of the El Niño-Southern Oscillation (ENSO) on winter precipitation in southern China is re-examined. The results show that positive correlation between ENSO and winter precipitation in southern China after 1995 is significantly higher than that before 1995. Significant positive correlation is located mainly over the southern coastal areas of China before 1995, whereas the positive correlation extends northward to the Yangtze River basin after 1995. These changes in the relationship between ENSO and winter precipitation are related to the ENSO pattern and Philippine anticyclone changes. An increasing trend is observed in the ENSO amplitude, while the area with cooler SST in the Philippine seas extends westward after 1995 compared with that before 1995, leading to an extension of the anticyclone from the east side to the west side of the Philippines. The westward extension of anticyclone after 1995 could enhance the winter precipitation over southern China through modifying water vapour fluxes and vertical motion. Model results support the observation analyses of the changes in ENSO-precipitation relationship and the corresponding mechanism. The mean SST changes could also modify the ENSO-precipitation relationship.

The development of radioresistance by nasopharyngeal carcinoma (NPC) cells almost always results in tumor recurrence and metastasis, making clinical treatment of the disease difficult. In this study, the mechanism of radioresistance in NPC cells was investigated. First, a gene array and quantitative reverse-transcription-PCR assays were used to screen for genes exhibiting significantly altered expression in the DNA damage signaling pathway. Based on those results, GADD45G was further studied in the context of radioresistance. A GADD45G-knockout NPC cell line (CNE-2R-KO) was constructed using CRISPR-Cas9 technology and used for a comparison of differences in radioresistance with other radiosensitive and radioresistant NPC cells, as evaluated using colony formation assays. Cell cycle changes were observed using flow cytometry. Cell proliferation and migration were measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and wound healing assays, respectively. The sequencing results revealed the successful construction of the CNE-2R-KO cell line, the radiosensitivity of which was higher than that of its parent radioresistant cell line owing to the GADD45G knockout. This was likely related to the increase in the number of cells in the G1 phase and decrease in those in the S1 phase as well as the increased cell proliferation rate and decreased migratory ability. GADD45G is associated with radioresistance in NPC cells and likely has a role in the occurrence and metastasis of NPC.

Using the ERA-Interim reanalysis dataset for the time period 1979–2016, we analyzed the influence of the stratospheric polar vortex shift on the Arctic Oscillation (AO) in winter (December–March). The results show that a shift in the stratospheric polar vortex toward the Eurasian continent is favorable for the occurrence of the negative phase of the AO. The duration of the AO events accompanied by the stratospheric polar vortex shift toward the Eurasian continent (AO-shift events) is longer than that of the remaining negative AO events (AO-noshift events), and the intensity of AO-shift events is greater than that of AO-noshift events from day 4 to day 15 of the life cycle of the events. The enhancement in the AO intensity during AO-shift events is likely due to downward extension of the stratospheric northern annular mode (NAM) signals and more poleward-propagating planetary waves in the troposphere and lower stratosphere and their convergence in the mid-high latitudes. Furthermore, the polar vortex shift can lead to changes in the intensity of the three action centers in the AO spatial pattern at 500 hPa. In general, during AO-shift events, the three action centers are stronger than those during AO-noshift events. There is an overall westward shift of the Arctic action center during AO-shift events, which may be closely related to the changes of Greenland blocking frequency.

Cu-foam sheets with the thicknesses of 0.15 mm and 0.5 mm were utilized as strengthening structure to improve the performances of the Sn3.0Ag0.5Cu (SAC305)/Cu solder joints. The ultrasonic-assisted soldering was applied to manufacture the solder joints. The effects of Cu-foam and ultrasound-assisted soldering time on microstructure and mechanical property of solder joints were researched. Experimental results showed that excellent metallurgical bonding was generated between the copper substrate and the Cu-foam/SAC305 composite solder layer. The average thickness of interfacial intermetallic compound (IMC) layer decreased with the increase of ultrasonically soldering time, and a thinner interfacial IMC layer was found in the joints with ultrasonic treatment in narrow channels. With the ultrasonic soldering time prolonged, the Cu6Sn5 grains became more refined. Some round-shape Cu6Sn5 grains were transformed into hexagonal prismatic with the increase of the ultrasonic soldering time. The shear test was conducted for the solder joints under different soldering conditions. It was found that the shear strength of the Cu-foam/SAC305 composite solder joints were higher than that of SAC305 solder joints. The grain refinement caused by ultrasonic cavitation significantly improved the shear strength of the solder joints. Besides, the fracture behavior of solder joints without ultrasonic vibration was classified to be ductile-brittle mixed type while that with ultrasonic vibration was changed to be ductile type.

It remains unknown for decades how some of the therapeutic fusion proteins positive in a small percentage of cancer cells account for patient outcome. Here, we report that osteosarcoma Rab22a-NeoF1 fusion protein, together with its binding partner PYK2, is sorted into exosomes by HSP90 via its KFERQ-like motif (RVLFLN142). The exosomal Rab22a-NeoF1 fusion protein facilitates the pulmonary pre-metastatic niche formation by recruiting bone marrow-derived macrophages. The exosomal PYK2 activates RhoA in its negative recipient osteosarcoma cells and induces signal transducer and activator of transcription 3 activation in its recipient macrophages to increase M2 phenotype. Consequently, lung metastases of its recipient osteosarcoma cells are promoted by this exosomal Rab22a-NeoF1 fusion protein, and this event can be targeted by disrupting its interaction with PYK2 using a designed internalizing RGD peptide.

Osteosarcoma is a type of aggressive malignant bone tumour that frequently metastasizes to lungs, resulting in poor prognosis. However, the molecular mechanisms of lung metastasis of osteosarcoma remain poorly understood. Here we identify exon-intron fusion genes in osteosarcoma cell lines and tissues. These fusion genes are derived from chromosomal translocations that juxtapose the coding region for amino acids 1-38 of Rab22a (Rab22a1-38) with multiple inverted introns and untranslated regions of chromosome 20. The resulting translation products, designated Rab22a-NeoFs, acquire the ability to drive lung metastasis of osteosarcoma. The Rab22a1-38 moiety governs the function of Rab22a-NeoFs by binding to SmgGDS-607, a GTP-GDP exchange factor of RhoA. This association facilitates the release of GTP-bound RhoA from SmgGDS-607, which induces increased activity of RhoA and promotes metastasis. Disrupting the interaction between Rab22a-NeoF1 and SmgGDS-607 with a synthetic peptide prevents lung metastasis in an orthotopic model of osteosarcoma. Our findings may provide a promising strategy for a subset of osteosarcoma patients with lung metastases.

Using the JRA-55 reanalysis datasets and radiosonde observations, the impact of the quasi-biennial oscillation (QBO) on the downward extension of stratospheric Northern Annular Mode (NAM) signals in its positive and negative phases (positive and negative NAM hereafter) is examined. The results show that the average number of days per month on which stratospheric negative NAM signals extend downward into the troposphere is more than twice as large during the easterly phase of the QBO (EQBO) as those during the westerly phase of the QBO (WQBO). The increasing likelihood of downward extension of stratospheric negative NAM signals during the EQBO is related to three factors: enhanced upward wave-1 fluxes entering the stratosphere, anomalous poleward wave fluxes below 100 hPa and EQBO-induced residual circulation. It is also revealed that the EQBO-induced subtropical tropospheric easterly anomalies lead to positive height anomalies over the subtropical North Atlantic, which are amplified by transient eddies and maintained by convection. These subtropical positive height anomalies further stimulate an anomalous wave train, forcing subpolar positive height anomalies over the Euro-Atlantic sector and enhancing wave 1. Over the Pacific, the EQBO could also induce positive height anomalies in the tropical troposphere, and these anomalies are related to convection and vertical motion. The positive height anomalies can induce anomalous poleward-propagating waves, forcing negative height anomalies over the North Pacific at mid-high latitudes and the enhancing wave 1. Fewer stratospheric positive NAM signals extend downward into the troposphere during the EQBO than during the WQBO, with mechanisms similar to those of negative NAM.

Using ERA-Interim and ERA-5 reanalysis datasets combined with measurements from the Microwave Limb Sounder (MLS), we divided the Tibetan Plateau (TP) into three regions to analyse the long-term trends of water vapor in the upper troposphere and its possible mechanisms. The conclusions are as follows. The water vapor at 200 hPa in the summers from 1979 to 2016 over Region 1 (34°N-40°N, 80°E-100°E) shows a positive trend, which is caused by the rising surface temperature and the northward shift of the South Asian High (SAH). The positive trend of water vapor over Region 2 (28°N-33°N, 80°E-90°E) is attributed to the enhanced South Asian summer monsoon, which leads to increases in horizontal transport of water vapor and vertical water vapor flux. The increase in the vertical transport of water vapor is responsible for the increase in water vapor over the Region 2. The negative trend of water vapor over Region 3 (27°N-30°N, 93°E-98°E) is mainly due to the weakening of water vapor transport caused by the weakening of convective activities.

Using various observations, reanalysis datasets, and a general circulation model (CESM-WACCM4), the relationship between the Arctic total column ozone (TCO) and the tropospheric circulation and sea surface temperatures (SSTs) over the western North Pacific (30°–45°N, 130°E–170°W) was investigated. We find that anomalies in the circulation and SSTs over the western North Pacific in June are closely related to anomalies in the Arctic TCO in March; that is, when the Arctic TCO in March decreases, the anomalous tropospheric cyclone and negative SST anomalies (SSTAs) will occur over the western North Pacific in June. Further analysis indicates that the decreased Arctic TCO in March tends to result in positive Victoria mode (VM)-like SSTAs over the North Pacific in April, which persist and develop an anomalous cyclone over the eastern North Pacific in May via atmosphere–ocean coupling. This anomalous cyclone over the eastern North Pacific subsequently induces an anomalous cyclone over the western North Pacific in June via westward-propagating Rossby waves in the lower troposphere. Furthermore, the negative SSTAs over the western North Pacific are enhanced by the anomalous northerly wind related to the anomalous cyclone in June. The effects of increased Arctic TCO in March on the tropospheric circulation and SSTs are almost opposite to those of decreased Arctic TCO. These results are also supported by our numerical simulations. Moreover, 10%–20% of the anomalies in the tropospheric circulation and SSTs over the western North Pacific in June are affected by the anomalies in the Arctic TCO in March.

Osteosarcoma, an aggressive malignant cancer, has a high lung metastasis rate and lacks therapeutic target. Here, we reported that chromobox homolog 4 (CBX4) was overexpressed in osteosarcoma cell lines and tissues. CBX4 promoted metastasis by transcriptionally up-regulating Runx2 via the recruitment of GCN5 to the Runx2 promoter. The phosphorylation of CBX4 at T437 by casein kinase 1α (CK1α) facilitated its ubiquitination at both K178 and K280 and subsequent degradation by CHIP, and this phosphorylation of CBX4 could be reduced by TNFα. Consistently, CK1α suppressed cell migration and invasion through inhibition of CBX4. There was a reverse correlation between CK1α and CBX4 in osteosarcoma tissues, and CK1α was a valuable marker to predict clinical outcomes in osteosarcoma patients with metastasis. Pyrvinium pamoate (PP) as a selective activator of CK1α could inhibit osteosarcoma metastasis via the CK1α/CBX4 axis. Our findings indicate that targeting the CK1α/CBX4 axis may benefit osteosarcoma patients with metastasis., Osteosarcoma is an aggressive tumour and little is known the mechanisms underpinning its highly metastatic nature. Here, the authors highlight a role for the CK1α/CBX4 axis in driving metastasis, suggesting that this pathway might be targeted for therapeutic benefit.