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Utilizing the European Centre for Medium-Range Weather Forecast (ECMWF) Reanalysis v5 (ERA5), for the first time, we have confirmed close links among Sudden Stratospheric Warmings (SSWs) in the Northern Hemisphere (NH), the polar vortices, and stratospheric Planetary Waves (PWs) by analyzing and comparing their trends. Interestingly, within overall increasing trends, the duration and strength of SSWs exhibit increasing and decreasing trends before and after the winter of 2002, respectively. To reveal possible physical mechanisms driving these trends, we analyzed the long-term trends of the winter (from December to February) polar vortices and of stratospheric PWs with zonal wave number 1. Notably, our results show that in all three time periods (the entire period of 41 winters, 1980 to 2020, and the two subperiods — 1980−2002 and 2002−2020) enhancing SSWs were always accompanied by weakening winter polar vortices and strengthening polar PWs like Stationary Planetary Waves (SPWs) and 16-day waves, and vice versa. This is the first proof, based on ERA5 long-term trend data, that weakening polar vortices and enhancing stratospheric PWs (especially SPWs) could cause an increase in SSWs.

Abstract Development of B cell memory is a conundrum that scientists are still exploring. Studies have been conducted in vitro and using advanced animal models to elucidate the mechanism underlying the generation of memory B cells (MBCs), the precise roles of MBCs against pathogens, and their protective functions against repeated infections throughout life. Lifelong immunity against invading diseases is mainly the result of overcoming a single infection. This protection is largely mediated by the two main components of B cell memory—MBCs and long-lived plasma cells (PCs). The chemical and cellular mechanisms that encourage fat selection for MBCs or long-lived PCs are an area of active research. Despite the fact that nearly all available vaccinations rely on the capacity to elicit B-cell memory, we have yet to develop successful vaccines that can induce broad-scale protective MBCs against some of the deadliest diseases, including malaria and AIDS. A deeper understanding of the specific cellular and molecular pathways that govern the generation, function, and reactivation of MBCs is critical for overcoming the challenges associated with vaccine development. Here, we reviewed literature on the development of MBCs and their reactivation, interaction with other cell types, strategies against invading pathogens, and function throughout life and discussed the recent advances regarding the key signals and transcription factors which regulate B cell memory and their relevance to the quest for vaccine development.

Abstract Traumatic brain injuries (TBI) and stroke are major causes of morbidity and mortality in both developing and developed countries. The complex and heterogeneous pathophysiology of TBI and cerebral ischemia‐reperfusion injury (CIRI), in addition to the blood‐brain barrier (BBB) resistance, is a major barrier to the advancement of diagnostics and therapeutics. Clinical data showed that the severity of TBI and stroke is positively correlated with the number of neutrophils in peripheral blood and brain injury sites. Furthermore, neutrophil extracellular traps (NETs) released by neutrophils correlate with worse TBI and stroke outcomes by impairing revascularization and vascular remodeling. Therefore, targeting neutrophils to deliver NETs inhibitors to brain injury sites and reduce the formation of NETs can be an optimal strategy for TBI and stroke therapy. Herein, the study designs and synthesizes a reactive oxygen species (ROS)‐responsive neutrophil‐targeting delivery system loaded with peptidyl arginine deiminase 4 (PAD4) inhibitor, GSK484, to prevent the formation of NETs in brain injury sites, which significantly inhibited neuroinflammation and improved neurological deficits, and improved the survival rate of TBI and CIRI. This strategy may provide a groundwork for the development of targeted theranostics of TBI and stroke.

Abstract Ischemic stroke is a refractory disease that endangers human health and safety owing to cerebral ischemia. Brain ischemia induces a series of inflammatory reactions. Neutrophils migrate from the circulatory system to the site of cerebral ischemia and accumulate in large numbers at the site of inflammation across the blood–brain barrier. Therefore, hitchhiking on neutrophils to deliver drugs to ischemic brain sites could be an optimal strategy. Since the surface of neutrophils has a formyl peptide receptor (FPR), this work modifies a nanoplatform surface by the peptide cinnamyl‐F‐(D)L‐F‐(D)L‐F (CFLFLF), which can specifically bind to the FPR receptor. After intravenous injection, the fabricated nanoparticles effectively adhered to the surface of neutrophils in peripheral blood mediated by FPR, thereby hitchhiking with neutrophils to achieve higher accumulation at the inflammatory site of cerebral ischemia. In addition, the nanoparticle shell is composed of a polymer with reactive oxygen species (ROS)‐responsive bond breaking and is encased in ligustrazine, a natural product with neuroprotective properties. In conclusion, the strategy of hitching the delivered drugs to neutrophils in this study could improve drug enrichment in the brain, thereby providing a general delivery platform for ischemic stroke or other inflammation‐related diseases.

Abstract Based on the zonal winds from the Modern‐Era Retrospective Analysis for Research and Applications, version 2 reanalysis data, we investigate the enhancement of an eastward propagating 4‐day wave (E4DW) during the 2019 Antarctic sudden stratospheric warming (SSW). The amplitudes of E4DW are centered at 50°S and 50 km with a maximum amplitude of ∼20 m/s. The enhanced E4DW significantly exceeds the climatological level and has the strongest amplitude in the Southern Hemisphere since 1980. Our results show that the E4DW is generated by the atmospheric instabilities via a double‐jet configuration of the zonal mean zonal winds. Our analysis further indicates that the special structure of the zonal mean zonal winds caused by the 2019 Antarctic SSW at the stratopause is responsible for the excitation of the record‐strong E4DW in 2019 in the Southern Hemisphere.

Abstract Combining two meteor radar observations at mid-latitudes and MERRA2 reanalysis data, we report an extraordinary quasi-16-day wave (Q16DW) activity in the mesosphere and lower thermosphere (MLT) from about October 2013 to January 2014. The Q16DW is not only active for a long period, but also unrelated to stratospheric sudden warming (SSW), while 7-year radar observations indicate that strong waves and oscillations in the MLT at mid-latitudes occur generally in winter, and are almost always associated with SSW and stratospheric final warming (SFW), except the extraordinary Q16DW. Meanwhile, during the SSW and SFW in February and March 2014, the observation and reanalysis data show that an intense Q16DW arises in the stratosphere but is not present in the MLT. The two Q16DWs are obviously distinguished from each other. The exceptional Q16DW shows a slowly downward phase progression from the MLT to the troposphere with predominant wavenumber 1, while the second Q16DW has a steeper vertical phase in the stratosphere with predominant wavenumber 2. Although the eastward winds prevail, these Q16DWs are weakened and evanescent in the region with the westward wind and negative refractive index. EP flux vector indicates that these waves originate mainly from the lower atmosphere at mid- and high-latitudes, and are intensified in the middle stratosphere. The first Q16DW may make a little contribution to polar vortex intensification due to small EP flux divergence. However, the Q16DW in the SSW has a strong negative divergence almost in the whole polar stratosphere, implying an important role in the stratospheric zonal wind reduction in the SSW. Graphical Abstract

Abstract The global amplitude of the westward propagating quasi-16-day waves (16DW) with wavenumber 1 (Q16W1), the strongest component of 16DW, are derived from the European Centre for Medium-Range Weather Forecasts ERA-Interim reanalysis temperature and zonal wind data sets from February 1979 to January 2018. In terms of temperature and zonal wind, strong climatologically average amplitudes of Q16W1 appear in the upper stratosphere at mid–high latitudes in both hemispheres, and the wave amplitude is stronger in the Northern Hemisphere (NH) than in the Southern Hemisphere (SH). Multivariate linear regression is separately applied to calculate the responses of the Q16W1 temperature and zonal wind amplitudes to the QBO (quasi-biennial oscillation), ENSO (El Niño-Southern Oscillation), solar activity and linear trends of the Q16W1 amplitude. The QBO signatures of the Q16W1 temperature and zonal wind amplitudes are mainly located in the stratosphere. The Q16W1 has significant QBO responses at low latitudes. In addition, only the temperature amplitude presents a larger QBO signature in its strongest climatological amplitude region. No significant responses to ENSO and solar activity are observed in temperature and zonal wind amplitudes. The linear trends of the monthly mean Q16W1 temperature and zonal wind amplitude are generally positive, especially in the mid-upper stratosphere. The trend is asymmetric about the equator and significantly stronger in the NH than in the SH. The seasonal variation in the trend of the temperature amplitude is studied and illustrated to be stronger in winter and weaker in spring and autumn. Further investigation suggests that the background and local instability trends contribute most of the increasing trend of the Q16W1 amplitude. In winter in both hemispheres, a weakening trend of eastward zonal wind provides more favourable background wind for Q16W1 upward propagation, in autumn and winter in the NH and in spring, autumn and winter in the SH, and the increasing trend of local instability may enhance wave excitation. Graphical Abstract

Abstract Using meteor radar, radiosonde observations and MERRA-2 reanalysis data from 12 August to 31 October 2006, we report a dynamical coupling from the tropical lower atmosphere to the mesosphere and lower thermosphere through a quasi-27-day intraseasonal oscillation (ISO). It is interesting that the quasi-27-day ISO is observed in the troposphere, stratopause and mesopause regions, exhibiting a three-layer structure. In the MLT, the amplitude in the zonal wind increases from about 4 ms−1 at 90 km to 15 ms−1 at 100 km, which is different from previous observations that ISOs occurs generally in winter with an amplitude peak at about 80–90 km, and then are rapidly weakened with increasing height. Outgoing longwave radiation (OLR) and specific humidity demonstrate that there is a quasi-27-day periodicity in convective activity in the tropics, which causes the ISO of the zonal wind and gravity wave (GW) activity in the troposphere. The upward propagating GWs are further modulated by the oscillation in the troposphere and upper stratosphere. As the GWs propagate to the MLT, the quasi-27-day oscillation in the wind field is induced with a clear phase opposite to that in the lower atmosphere through instability and dissipation of these modulated GWs. Wavelet analysis shows that the quasi-27-day variability in the MLT appears as a case event rather than a persistent phenomenon, and has not a clear corresponding relation with the solar rotation effect within 1 year of observations.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Emerging therapies, such as ferroptosis mediated cancer therapy and phototherapy, offer new opportunities for HCC treatment. The combination of multiple treatments is often more effective than monotherapy, but many of the current treatments are prone to serious side effects, resulting in a serious decline in patients’ quality of life. Therefore, the combination therapy of tumor in situ controllable activation will improve the efficacy and reduce side effects for precise treatment of tumor. Herein, we synthesized a GSH-activatable nanomedicine to synergize photothermal therapy (PTT) and ferrotherapy. We utilized a near-infrared dye SQ890 as both an iron-chelating and a photothermal converter agent, which was encapsulated with a GSH-sensitive polymer (PLGA-SS-mPEG), to attain the biocompatible SQ890@Fe nanoparticles (NPs). In the tumor microenvironment (TME), SQ890@Fe NPs showed a GSH-activated photothermal effect that could increase the Fenton reaction rate. Meanwhile, the depletion of GSH could further increase ferroptosis effect. In turn, the increasing radical generated by ferrotherapy could impair the formation of heat shock proteins (HSPs) which could amplify PTT effects by limiting the self-protection mechanism. Overall, the intelligent nanomedicine SQ890@Fe NPs combines ferrotherapy and PTT to enhance the efficacy and safety of cancer treatment through the mutual promotion of the two treatment mechanisms, providing a new dimension for tumor combination therapy.

Anomalous changes of zonal wind quasi-biennial oscillation (QBO) in winter 2015−2016 have received close attention. Combining radiosonde and satellite observations and reanalysis data, we investigate anomalous changes in temperature and ozone QBOs from the lower to middle stratosphere. As wind shear direction is reversed due to unexpected changes of zonal wind QBO at about 24−30 km, the shortest cold phase at 21−27 km appears in temperature QBO. This is different from the completely interrupted westward phase in zonal wind QBO, while the longest cold phase above almost 27 km lasts for 2−3 years from 2015 to 2017, owing to the absence of corresponding warm phase. Meridional scale reduction of temperature QBO causes a small temperature anomaly, thus the thermal wind relationship looks seemingly different from that in the other regular QBO cycles. QBO in the ozone mixing ratio anomaly shows a double-peak with inverse phase, and its phase below (above) 30 km is in agreement with (opposite to) the phase of temperature QBO because of different control mechanisms of ozone. Following temperature QBO variation, QBO in the ozone mixing ratio anomaly exhibits a less positive phase at 20−30 km in 2016−2017, and a very long positive phase above 30 km from 2015 to 2017. QBO in total column ozone shows a small peak in winter 2016−2017 since ozone is mainly concentrated at 20 to 30 km. Anomalous changes of temperature and ozone QBOs due to unexpected QBO zonal wind variation can be well-explained according to thermal wind balance and thermodynamic balance.

Abstract We analyze global characteristics of the westward-propagating quasi-16-day wave (Q16DW) with zonal wavenumber 1 (W1) in the troposphere and stratosphere using zonal wind, meridional wind, vertical velocity, temperature, geopotential, and potential vorticity data from the European Centre for Medium-Range Weather Forecasts (ECMWF) Interim Re-Analysis during one year from December 2012 to November 2013. The amplitudes of the W1 Q16DW are larger in the stratosphere than in the troposphere, and remarkable amplitudes are found at middle and high latitudes in the Northern Hemisphere (NH). More detailed analyses on the temporal variation in the W1 Q16DW show that this wave is significantly enhanced during the 2012/2013 Stratospheric Sudden Warming (SSW) event, and the strong wave most likely provides additional forcing on the splitting of the displaced polar vortex. Analysis of the Eliassen–Palm flux (EP flux) and its divergence of the interaction between W1 Q16DW and quasi-stationary planetary waves with wavenumber 1 during the 2012/2013 SSW event reveals that it causes an upward heat flux and exerts a westward acceleration on the background winds, indicating that this interaction plays an important role in the eastward stratospheric jet reversal. Moreover, the wave is amplified in the occurrence region of barotropic and/or baroclinic instability, suggesting a local source of the growing W1 Q16DW during this SSW event.

Abstract The eastward- and westward-traveling 10-day waves with zonal wavenumbers up to 6 from surface to the middle mesosphere during the recent 12 years from 2007 to 2018 are deduced from MERRA-2 data. On the basis of climatology study, the westward-propagating wave with zonal wave number 1 (W1) and eastward-propagating waves with zonal wave numbers 1 (E1) and 2 (E2) are identified as the dominant traveling ones. They are all active at mid- and high-latitudes above the troposphere and display notable month-to-month variations. The W1 and E2 waves are strong in the NH from December to March and in the SH from June to October, respectively, while the E1 wave is active in the SH from August to October and also in the NH from December to February. Further case study on E1 and E2 waves shows that their latitude–altitude structures are dependent on the transmission condition of the background atmosphere. The presence of these two waves in the stratosphere and mesosphere might have originated from the downward-propagating wave excited in the mesosphere by the mean flow instability, the upward-propagating wave from the troposphere, and/or in situ excited wave in the stratosphere. The two eastward waves can exert strong zonal forcing on the mean flow in the stratosphere and mesosphere in specific periods. Compared with E2 wave, the dramatic forcing from the E1 waves is located in the poleward regions.

Using Modern-Era Retrospective analysis for Research and Applications, Version 2 (MERRA-2) data in the northern hemisphere at the 10 hPa level, we compared the stratospheric evolution of temperature and geopotential height during two major sudden stratosphere warming events (SSWs) that occurred in the Arctic winter of 2018 and 2019. In the prewarming period, poleward temperature-enhanced regions were mainly located around 120°E with a displaced vortex and around 120°E and 60°W with splitting vortices. The evolution of geopotential height indicated that these temperature-enhanced regions were both on the western side of high-latitude anticyclones. In the postwarming period, the polar vortex turned from splitting to displacement in the 2018 SSW but from displacement to splitting in the 2019 SSW. Both transitions were observed over the Atlantic region, which may have been caused by anticyclones moving through the polar region. Our findings revealed that the evolution of the anticyclone is important during SSWs and is closely related to temperature-enhanced regions in the prewarming periods and to transitions of the polar vortices in postwarming periods.

This study presents an analysis of the quasi-16-day wave (Q16DW) at three stations in the middle latitudes by using a meteor radar chain in conjunction with Aura Microwave Limb Sounder temperature data and MERRA2 (Modern-Era Retrospective Analysis for Research and Applications, Version 2) reanalysis data from 2008 to 2017. The radar chain consists of three meteor radar stations located at Mohe (MH, 53.5°N, 122.3°E), Beijing (BJ, 40.3°N, 116.2°E), and Wuhan (WH, 30.5°N, 114.6°E). The Q16DW wave exhibits similar seasonal variation in the neutral wind and temperature, and the Q16DW amplitude is generally strong during winter and weak around summer. The Q16DW at BJ was found to have secondary enhancement around September in the zonal wind, which is rarely reported at similar latitudes. The latitudinal variations of the Q16DW in the neutral wind and temperature are quite different. The Q16DW at BJ is the most prominent in both neutral wind components among the three stations and the Q16DW amplitudes at MH and WH are comparable, whereas the wave amplitude in temperature decreases with decreasing latitude. The quasi-geostrophic refractive index squared at the three stations in the period from 2008 to 2017 was revealed. The results indicate that the Q16DW in the mesosphere and lower thermosphere (MLT) at MH has a limited contribution from the lower atmosphere. Around March and October, the Q16DW in the troposphere at BJ can propagate upward into the MLT region, whereas at WH, the contribution to the Q16DW in the MLT region is largely from the mesosphere.

Cisplatin is a common chemotherapeutic drug that has been used to treat of numerous tumors, including testicular, lung, bladder, ovarian, liver and head and neck cancers. Although clinical chemotherapy based on cisplatin has shown a remarkable therapeutic effect, the resistance to cisplatin becomes increasingly obvious as a patient uses it for a prolonged period. It not only affects the prognosis of these tumors, but also causes the recurrence of cancer and decreases the overall survival rate. The development of cisplatin resistance involves several mechanisms, including DNA damage repair, ATP-binding cassette (ABC) transporter, autophagy, cancer stem cells (CSCs), epithelial–mesenchymal transition (EMT), and other related signaling pathways. Interestingly, these mechanisms have been found to be influenced by circular RNAs (circRNAs) to regulate tumor proliferation, invasion, chemosensitivity, and other biological behaviors in the tumor microenvironment (TME). In recent years, circRNAs in cisplatin resistance in tumors, especially lung cancer and gastric cancer, have gradually drawn peoples’ attention. This review summarizes recent studies on the functions and mechanisms of circRNAs in cisplatin resistance. We emphasize that circRNA can be used as a promising target gene to improve drug resistance and therapeutic efficacy.

Although the characteristics of the traveling 10-day waves (10DWs) above the middle stratosphere have been well explored, little research has been performed on the counterpart in the troposphere and lower stratosphere (TLS). In the present study, we use radiosonde observations and MERRA-2 data from 2020 to characterize traveling 10DWs in mid-latitudes in the TLS. Single-site observations in both hemispheres show that strong 10DW activities are always accompanied by strong eastward jets (10–13 km). MERRA-2 data indicate that in the troposphere, the eastward-propagating modes with larger wavenumbers, i.e., E3, E4, E5 and E6 are dominant, while in the lower stratosphere, the eastward- and westward-propagating modes with small zonal wavenumbers, e.g., 1 and 2, are dominant. Further research on E3, E4, E5 and E6 modes in the troposphere of both hemispheres shows that all the wave activities are positively correlated to the background zonal wind. The refractive index squared reveals that a strong eastward jet is suitable for these four modes to propagate. However, just above the jet, the eastward wind decreases with altitude, and a thick evanescence region emerges above 15 km. E3, E4, E5 and E6 10DWs cannot propagate upward across the tropopause; as such, this can explain why these four modes are weak or even indiscernible in the stratosphere and above. In the troposphere, E5 10DW at 32° S was the most dominant mode in 2020. A case study of the anomalously strong E5 10DW activity on 12 May 2020 indicates that the wave amplification resulted from the upward and equatorward transmission of wave energy flows. Moreover, the tropopause and equatorial region can prevent the propagations of wave energy flows of E5 10DW. The upward-propagating wave energy is deposited near the tropopause, resulting in significant short-term variability in the tropopause height.

Abstract Background Cancer-associated fibroblasts (CAFs) have been widely reported to promote tumor angiogenesis. However, the underlying mechanisms of the proangiogenic switch of CAFs remain poorly understood. This study aims to clarify the mechanisms underlying the proangiogenic switch of CAFs. Methods NIH/3T3 cells were treated with B16 and B16F10-derived exosomes. Then the CAFs markers and proangiogenic factors were detected by RT-PCR and Western blot. CCK-8 assay, transwell migration assay, tube formation assay, and in vivo Matrigel plug assay were conducted to determine the proangiogenic capability of CAFs. Western blot and AG490 were used to investigate the role of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the proangiogenic switch of CAFs. Bioinformatics analysis, luciferase reporter assay, microRNA mimic and inhibitor, and xenograft models were used to investigate the role of mmu-miR-155-5p (miR-155) in the proangiogenic switch of CAFs. Results In this study, we show that melanoma cell-secreted exosomes can induce reprogramming of fibroblasts into CAFs and that exosomal miR-155 can trigger the proangiogenic switch of CAFs. Mechanistically exosomal miR-155 can be delivered into fibroblasts and promote the expression of proangiogenic factors, including vascular endothelial growth factor A (VEGFa), fibroblast growth factor 2 (FGF2), and matrix metalloproteinase 9 (MMP9), by directly targeting suppressor of cytokine signaling 1 (SOCS1). Downregulation of SOCS1 activates JAK2/STAT3 signaling pathway and elevates the expression levels of VEGFa, FGF2, and MMP9 in fibroblasts. Treatment with exosomes containing overexpressed miR-155 can promote angiogenesis, and the reduction of miR-155 in melanoma cell-secreted exosomes alleviates angiogenesis in vitro and in vivo. Conclusions These results demonstrate that by promoting the expression of proangiogenic factors in recipient fibroblasts via SOCS1/JAK2/STAT3 signaling pathway, melanoma cell-secreted exosomal miR-155 can induce the proangiogenic switch of CAFs. Although tumor angiogenesis is modulated by various factors, exosomal miR-155 may be a potential target for controlling melanoma angiogenesis and used to set up novel strategies to treat melanoma.

Vertical wave number spectra of inertial gravity waves in the troposphere and lower stratosphere over six stations at latitudes from 20° N to 40° N were statistically studied by using the data from Radiosonde observation on a twice daily basis at 08:00 and 20:00 LT. Statistically, the spectral characteristics seem to be independent of the local observation time, and show considerable conformity between the spectral of zonal and meridional kinetic energy densities. Compared with the spectra of the kinetic energy density, the spectra of the potential energy density are steeper. in addition the characteristic wave numbers of the spectra also show considerable consistency among the observations at different stations. As for the spectral slopes, they are systematically smaller (in magnitude) than the canon value of –3, and exhibit slight height, seasonal and latitudinal variability. In addition to these universal characteristics, the spectral structures also exhibit departures and variations, and most of the departures and variations are related to the strong tropospheric jets. Generally, in the case of strong shear due to the tropospheric jet, there usually occur larger characteristic wave numbers and smaller spectral slopes. These departures seem to be persistent and climatological rather than transitory, indicating the significant impacts of the sheared background winds on the spectral structures of gravity waves.

Traveling quasi-5-day oscillations (Q5DOs) with different wavenumbers are independently observed in the mesosphere and the lower thermosphere during many recent sudden stratospheric warming (SSW) events, but their common activities during SSWs are still unclear. Based on the geopotential height data measured by the Aura/Microwave Limb Sounder (MLS) from August 2004 to March 2021, we statistically investigate the characteristics of the Q5DOs during eight Arctic major SSW events. The amplitudes of the Q5DOs are obtained by a new fitting method, which inhibits the effect of rapid changes in stationary planetary waves during SSWs. Our results reveal a robust feature that Q5DOs were enhanced during all interested SSW events. Our analysis indicates that eastward and westward propagating Q5DOs can be simultaneously enhanced during SSWs. Additionally, the wavenumbers of the enhanced Q5DOs are found to be associated with the geometry of polar vortices. Extremely strong westward Q5DOs with wavenumber 2 are consistently observed during split-type major SSWs. [ABSTRACT FROM AUTHOR]