bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of a New Global Ocean Reanalysis in ENSO Predictions With NOAA UFS
Authors: Zhu Jieshun , Wang Wanqiu , Kumar Arun , Liu Yanyun , DeWitt David
Published: March 2024

As an update on the current NOAA/NCEP operational ocean reanalysis systems, a new system named GLobal Ocean Reanalysis (GLORe) is recently built up based on the JEDI‐SOCA 3DVar scheme. In this study, the quality of GLORe is assessed in initializing ENSO predictions using the NOAA Unified Forecast System (UFS). In details, initialized by GLORe, 9‐month ensemble hindcasts are conducted from each May/November during 1982–2021. The ENSO prediction skill is compared to the current NOAA operational system CFSv2, suggesting that UFS initialized with GLORe has an improved skill in ENSO predictions. By conducting another set of hindcasts with UFS and the same initializations as CFSv2, it is found that the skill improvement is largely attributed to the ocean initialization with GLORe, but with some contributions from model improvements as well. The effect of ocean initializations is further confirmed by the superiority of GLORe over CFSR as validated against an objective analysis.
Thermoelastic Properties of Fe3+‐Rich Jeffbenite and Application to Superdeep Diamond Barometry
Authors: Qin Fei , Wang Fei , Smyth Joseph R. , Zhang Dongzhou , Xu Jingui , Jacobsen Steven D.
Published: March 2024

Jeffbenite (Mg3Al2Si3O12) is a tetragonal phase found in so far only in superdeep diamonds, and its thermoelastic parameters are a prerequisite for determining entrapment pressures as it is regarded as a potential indicator for superdeep diamonds. In this study, the thermoelastic properties of synthetic Fe3+‐jeffbenite were measured up to 33.7 GPa and 750 K. High‐temperature static compression data were fitted, giving (∂KT0/∂T)P = −0.0107 (4) GPa/K and αT = 3.50 (3) × 10−5 K−1. The thermoelastic properties and phase stability are applied to modeling isomekes, or P‐T paths intersecting possible conditions of entrapment in diamond. We calculate that under ideal exhumation, jeffbenite entrapped at mantle transition zone conditions will exhibit a high remnant pressure at 300 K (Pinc) of ∼5.0 GPa. Elastic geobarometry on future finds of jeffbenite inclusions can use the new equation of state to estimate entrapment pressures for this phase with still highly uncertain stability field in the mantle.
How Currents Trigger Extreme Sea Waves. The Roles of Stokes Drift, Eulerian Return Flow, and a Background Flow in the Open Ocean
Authors: Li Yan , Chabchoub Amin
Published: March 2024

A deterministic system of ocean surface waves and flow in the oceanic boundary layer is key to understanding the dynamics of the upper ocean. For the description of such complex systems, a higher‐order shear‐current modified nonlinear Schrödinger equation is newly derived and then used to physically interpret the interplay between Stokes drift, Eulerian return flow due to a passing wave group, and an open‐ocean vertically sheared flow in the extreme sea wave generation. The conditions for the suppression or enhancement of the modulation instability in the rogue wave dynamics in the presence of a background flow are reported, whose relevance and influence to the Craik‐Leibovich type 2 instability in triggering a Langmuir‐type circulation is discussed. The findings highlight the need for future studies to establish and assess the energy transfer from waves to currents or in the reversing order, asserting a plausible physical mechanism for the dissipation of the surface wave energy through wave‐current interactions in the open ocean.
The Unprecedented 2023 North China Heatwaves and Their S2S Predictability
Authors: Xiao Huiwen , Xu Peiqiang , Wang Lin
Published: March 2024

This study unravels the characteristics, mechanisms, and predictability of four consecutive record‐breaking heatwaves hitting North China in June and July 2023. The first three heatwaves primarily influenced the northern part of North China and were accompanied by consistent anticyclonic anomalies in the upper troposphere. The anomalous anticyclone was caused by the British–Baikal corridor teleconnection along the polar front jet, particularly during the second heatwave. In contrast, the fourth heatwave was induced by a distinct low‐pressure system, attributed to the Silk Road pattern along the subtropical jet. The presence of this low‐pressure system and its interaction with atmospheric rivers and local topography led to the foehn wind, further contributing to the rise in surface temperatures. Sub‐seasonal to seasonal models can effectively predict the occurrence of all heatwaves 2–5 days in advance despite underestimating the intensity. However, models exhibit limitations in providing reliable predictions when the lead time exceeds 2 weeks.
Slow Electron Holes in the Earth's Magnetosheath
Authors: Shaikh Z. I. , Vasko I. Y. , Hutchinson I. H. , Kamaletdinov S. R. , Holmes J. C. , Newman D. L. , Mozer F. S.
Published: March 2024

We present a statistical analysis of electrostatic solitary waves observed aboard Magnetospheric Multiscale spacecraft in the Earth's magnetosheath. Applying single‐spacecraft interferometry to several hundred solitary waves collected in about 2‐minute interval, we show that almost all of them have the electrostatic potential of positive polarity and propagate quasi‐parallel to the local magnetic field with plasma frame velocities of the order of 100 km/s. The solitary waves have typical parallel half‐widths from 10 to 100 m that is between 1 and 10 Debye lengths and typical amplitudes of the electrostatic potential from 10 to 200 mV that is between 0.01% and 1% of local electron temperature. The solitary waves are associated with quasi‐Maxwellian ion velocity distribution functions, and their plasma frame velocities are comparable with ion thermal speed and well below electron thermal speed. We argue that the solitary waves of positive polarity are slow electron holes and estimate the time scale of their acceleration, which occurs due to interaction with ions, to be of the order of one second. The observation of slow electron holes indicates that their lifetime was shorter than the acceleration time scale. We argue that multi‐spacecraft interferometry applied previously to these solitary waves is not applicable because of their too‐short spatial scales. The source of the slow electron holes and the role in electron‐ion energy exchange remain to be established.
Large‐Scale Traveling Ionospheric Disturbances Over the European Sector During the Geomagnetic Storm on March 23–24, 2023: Energy Deposition in the Source Regions and the Propagation Characteristics
Authors: Nykiel Grzegorz , Ferreira Arthur , Günzkofer Florian , Iochem Pelin , Tasnim Samira , Sato Hiroatsu
Published: March 2024

Multiple Large‐Scale Traveling Ionospheric Disturbances (LSTIDs) are observed in the European sector in both day‐time and night‐time during the magnetic storm on March 23–24, 2023. The Total Electron Content (TEC) observation from a network of GNSS receivers shows the propagation of LSTIDs with amplitudes between around 0.5 and 1 TECU originating from auroral and polar cusp regions down to southern Europe (35°N) with velocities between around 500 and 1,600 [m/s]. We study the energy deposition to the LSTIDs in the source regions and the resulting horizontal propagation over storm‐time background density by using continuous measurements of EISCAT incoherent scatter radars in northern Norway and Svalbard that allow for estimating the source energy to the thermosphere‐ionosphere system via Joule heating and particle precipitation. Both EISCAT and GNSS TEC data show that the electron density decreased to 50% in the auroral zone after the storm onset. The ionospheric heating caused a nearly 250% increase in the electron temperature above 200 km altitude and the ion temperature above 100 km altitude. We find that Joule Heating acts as a primary energy source for the night‐time LSTIDs triggered in the auroral region, while the day‐time LSTIDs can be also driven by precipitating particles in the polar cusp. We also find that a significant background density decrease over the whole European sector is caused by this storm for the following day, during which almost no clear LSTIDs are observed.
Ion‐Scale Magnetic Flux Ropes and Loops in Earth's Magnetotail: An Automated, Comprehensive Survey of MMS Data Between 2017 and 2022
Authors: Smith A. W. , Sun W. , Slavin J. A. , Rae I. J.
Published: March 2024

Magnetic reconnection is a critically important process in defining the dynamics and energy transport within plasma environments. In near‐Earth space we may track where and when reconnection occurs by identifying associated coherent magnetic structures. On a global scale these structures facilitate the flow of mass and magnetic flux into, within, and out of the magnetospheric system, whilst contributing to local plasma heating. In the Earth's magnetotail there are two similar structures we identify in this work: magnetic flux ropes and loops. We present a robust, automated and model independent method by which encounters with such structures may be identified using the Magnetospheric Multiscale (MMS) mission. The magnetic structures are first identified through their magnetic field signatures at a single spacecraft (MMS1), including checks on the local minimum variance coordinate system. Next, the local curvature of the magnetic field is evaluated with all four MMS spacecraft. Finally, the plasma conditions are checked to ensure that the interpretation is fully self‐consistent. We evaluate the data obtained by MMS between 2017 and 2022. In total we find 181 self‐consistent magnetic flux ropes and 263 magnetic loops, which fit an exponentially decaying size distribution with a scale size comparable to the ion gyroradius (∼0.23 RE/1,400 km). If we remove the requirements on the plasma properties of the structure, we locate 648 potential magnetic flux ropes and 1,073 magnetic loops. The magnetic structures are preferentially observed in the pre‐midnight region of the magnetotail, with most identifications occurring beyond 20 RE. All catalogs are provided to the community.
Modeling the Global Distribution of Chorus Wave Induced Relativistic Microburst Spatial Characteristics
Authors: Kang Ning , Bortnik Jacob , Ma Qianli , Claudepierre Seth
Published: March 2024

The full spatiotemporal distribution of chorus wave‐induced relativistic electron microburst is modeled for chorus waves originated from different L shells and MLTs, based on the newly developed numerical precipitation model (Kang et al., 2022, https://doi.org/10.1029/2022gl100841). The wave‐particle interaction process that induces each microburst is analyzed in detail, and its relation to the chorus wave propagation effects is explained. The global distribution of maximum precipitation fluxes and scale sizes of relativistic microbursts is then obtained by modeling chorus waves at different L‐shells and local times. The characteristics of dawn and midnight sector microbursts have little difference, but the noon sector has much larger maximum flux and much smaller full width at half maximum, which may be due to dayside's low electron flux in the Landau resonance range. This suggests the controlling effect of keV electrons on the MeV electron precipitation intensity and properties and the overall relativistic electron loss in the outer radiation belt.
17O‐Excess in Tropical Cyclones Reflects Local Rain Re‐Evaporation More Than Moisture Source Conditions
Authors: Sun Chijun , Shanahan Timothy , He Shaoneng , Bailey Adriana , Nusbaumer Jesse , Hu Jun , Hillman Aubrey , Ornouski Erika , Warner Jacob , DeLong Kristine
Published: March 2024

17O‐excess is a relatively new water isotope parameter that could potentially provide useful information about the hydrological cycle. Previous works focusing on 17O‐excess in polar regions suggest that it primarily tracks moisture source relative humidity, but little is known about how to interpret 17O‐excess data in lower latitudes. Here we present quasi‐hourly triple oxygen isotope data of precipitation collected from two tropical cyclones in Texas and Louisiana in 2020 to understand the impacts of environmental and meteorological processes on the 17O‐excess of low‐to mid‐latitude precipitation. We find that at both hourly timescales and the event scale, 17O‐excess is strongly correlated to changes in on‐site rainfall intensity and relative humidity, which is consistent with the theory that the isotopic fractionation associated with rain re‐evaporation lowers the 17O‐excess of the remaining droplet. In addition, although evaporative conditions at the moisture source region may also influence 17O‐excess of water vapor transported to the precipitation site, their impacts are likely overprinted by the post‐condensation rain re‐evaporation processes. Our results thus suggest that 17O‐excess can be used as a proxy for local rather than source region evaporative conditions during tropical cyclones.
Raindrop Size Distributions Simulated Using a Bin Microphysics Scheme: Different Biases in Stratiform and Convective Rain From an Extratropical Cyclone
Authors: Lee Joohyun , Baik Jong‐Jin , Jin Han‐Gyul
Published: March 2024

Bin microphysics schemes prognose the raindrop size distribution (RSD), which can be directly evaluated through comparison with disdrometer observations. This evaluation will provide implications on the reliability of simulated cloud microphysics by bin microphysics schemes. In this study, the RSDs of a precipitation event associated with an extratropical cyclone passing South Korea are simulated using a bin microphysics scheme and compared with those observed by a ground‐based disdrometer. The simulated mean RSD overall agrees with the observation. However, notable overestimations appear in the large‐ (3.3–4.3 mm) and small‐ (0.56–1.88 mm) diameter ranges, which respectively stem from the biases in two different time periods, one dominated by stratiform rain and the other largely involved with convective rain. In the stratiform‐rain‐dominated period, the melting of snow is the largest contributor to RSDs. The overestimation in the large‐diameter range in this period can be associated with overly active ice–ice collection at upper levels, which generates a local maximum in RSD at the diameter of 3.3 mm that is not seen in the observed RSDs. In the convective‐rain‐involved period, the warm‐rain collision–coalescence is the largest contributor to RSDs. The overestimation in the small‐diameter range and underestimation in the large‐diameter range imply that the collisional growth of raindrops is represented to be weaker than that in reality. The findings in this study suggest that the RSDs simulated using a bin microphysics scheme can have some systematic biases associated with misrepresentation of some microphysical processes.
Analysis of Planetary Scale Waves Using Idealized Sudden Stratospheric Warming Simulations in Different Dynamical Cores
Authors: Park J.‐S. , Park S.‐H. , Chun H.‐Y. , Yoo J.‐H. , Shin U.
Published: March 2024

Planetary waves from the troposphere are known to play an important role in sudden stratospheric warming (SSW). To evaluate the representation of large‐scale waves in idealized SSW simulations, three dynamical cores of the National Center for Atmospheric Research Community Atmosphere Model were tested in this study: the Eulerian (EUL) spectral‐transform, finite‐volume (FV), and spectral element (SE) models. Notable differences were observed among the dynamical cores, with FV being unable to generate major SSWs and simulating minor SSWs less effectively than the other models. Wave decomposition analysis revealed distinct planetary wave propagation patterns during the development of each event. Zonal Wave Number 2 wave activities primarily determined SSW types, and ZWN1 led SSWs to recovery during the ensuing periods. However, FV failed to adequately propagate large‐scale waves in minor SSW events, preventing the reversal of stratospheric zonal‐mean zonal winds. Interestingly, FV showed decreased upward Eliassen–Palm flux compared to that of other dynamical cores, even during climatology. Additional tests were performed to examine the reasons for FV's atypical results, but the dynamic impacts on planetary waves remain poorly understood.
VIIRS Version 2 Deep Blue Aerosol Products
Authors: Lee Jaehwa , Hsu N. Christina , Kim Woogyung V. , Sayer Andrew M. , Tsay Si‐Chee
Published: March 2024

NASA's Deep Blue aerosol project has developed global aerosol data records using consistent retrieval algorithms applied to various satellite sensors. The primary components of these data records are derived from the series of Visible Infrared Imaging Radiometer Suite (VIIRS) aboard the Suomi National Polar‐orbiting Partnership (SNPP) and the National Oceanic and Atmospheric Administration or NOAA‐20+ satellites as well as the Moderate Resolution Imaging Spectroradiometer (MODIS), among others. These instruments provide over 23 years of measurements with similar radiometric characteristics for aerosol retrievals. The algorithms used for the initial Version 1 SNPP VIIRS data set were based on the MODIS Collection 6.1 Deep Blue algorithm over land and Satellite Ocean Aerosol Retrieval (SOAR) algorithm over water. For VIIRS Version 2 data reprocessing, major updates have been made to the algorithm suite, including better accounting for effects of surface pressure, improved determination of surface reflectance, and the inclusion of fine‐mode aerosol optical models to better represent anthropogenic aerosols over land. Cross‐calibration gain factors are derived for the NOAA‐20 VIIRS measurements to be consistent with the SNPP VIIRS, which allows the use of a unified algorithm package for both instruments. Comparisons against AERONET observations indicate that the Version 2 AOD data from SNPP VIIRS are significantly better than the Version 1 counterpart over land and slightly degraded over water in exchange for better spatial coverage. The AOD data from SNPP and NOAA‐20 VIIRS are comparable, indicating that cross‐calibration enables the creation of consistent aerosol data records using the series of VIIRS sensors.
Sediment Addition Leads to Variable Responses in Temperate Salt Marsh Greenhouse Gas Fluxes During the Growing Season
Authors: Bartolucci Nia N. , Fulweiler Robinson W.
Published: March 2024

Salt marshes play an important role in coastal carbon cycling. Unfortunately, these systems are threatened by sea level rise. One strategy to increase the resilience of marshes is thin‐layer placement of sediment (TLP). While TLP can boost elevation, little is known about how TLP alters greenhouse gas fluxes. We addressed this knowledge gap by measuring greenhouse gas fluxes in TLP plots that received either 7 cm (TLP‐7 cm) or 14 cm of added sediment (TLP‐14 cm), control plots that received no sediment, and reference plots that served as elevation end goal targets for the TLP plots. We found that mean (± standard error) CO2 uptake was comparable between control and TLP plots (control: −25.84 ± 2.46; TLP‐7 cm: −24.44 ± 3.32; TLP‐14 cm: −23.18 ± 2.08 mmol m−2 hr−1) and significantly less in reference plots (−9.54 ± 2.98 mmol m−2 hr−1). However, TLP plots (TLP‐7 cm: 35.74 ± 12.70, TLP‐14 cm: 19.79 ± 3.47 μmol m−2 hr−1) emitted up to 7 to 22 times more CH4 compared to control (5.77 ± 0.74 μmol m−2 hr−1) and reference (1.63 ± 0.75 μmol m−2 hr−1) plots, respectively. N2O fluxes from the TLP plots exhibited both uptake (TLP‐7 cm) and emission (TLP‐ 14 cm). Overall, the marsh remained a net greenhouse gas sink, at least during the times we measured—during the day and throughout the growing season. This research demonstrates the dynamics of greenhouse gas fluxes in marshes amended with sediment and highlights the need for future diel and annual measurements.
Pliocene Weakening of Gradients in Temperature but Not in Productivity in the Eastern Equatorial Pacific
Authors: Kimble K. M. , Herbert T. D. , Jones C. A.
Published: March 2024

The modern eastern equatorial Pacific Ocean (EEP) exhibits strong upwelling, producing pronounced gradients in sea surface temperature (SST), nutrient concentration, and biological productivity between 80° and 140°W. During the globally warmer late Pliocene (3.0–3.6 Ma), the EEP may have experienced permanent El Niño‐like conditions, supported by a reduced SST gradient across the equatorial Pacific. However, the weakened east‐west SST gradient has been controversial, with disparate results depending on the proxy used to monitor Western Warm Pool SSTs. We present new Pliocene alkenone‐based SST and paleoproductivity records from four Ocean Drilling Program (ODP) cores spanning an east‐west transect across the EEP, which present an internally consistent picture of SST and productivity gradients in the modern cold tongue, resolved at orbital‐scale variability. Strong agreement between core top reconstructions and satellite estimates indicates that alkenone paleotemperature and paleoproductivity proxies are appropriate for reconstructing Pliocene EEP conditions. The average SST gradient between 90° and 120°W was reduced from the modern 1.8°C gradient to 0.9°C in the late Pliocene. Despite the weakened SST gradient, the surface productivity gradient was stronger during the late Pliocene compared to modern, based on calibrated X‐ray fluorescence biogenic opal and alkenone average accumulation rates. Contrary to modern El Niño SST and productivity patterns, reduced Pliocene surface productivity did not accompany the weakened SST gradient. Instead, strong Pliocene biogenic opal and alkenone concentration accumulation gradients in the eastern EEP suggest that subsurface tilting of the nutricline and thermocline persisted to supply vigorous upwelling of warm but nutrient‐rich subsurface waters in a warmer climate.
Modeling Ionospheric TEC Using Gradient Boosting Based and Stacking Machine Learning Techniques
Authors: Nigusie Ayanew , Tebabal Ambelu , Galas Roman
Published: March 2024

Accurately predicting and modeling the ionospheric total electron content (TEC) can greatly improve the accuracy of satellite navigation and positioning and help to correct ionospheric delay. This study assesses the effectiveness of four different machine learning (ML) models in predicting hourly vertical TEC (VTEC) data for a single‐station study over Ethiopia. The models employed include gradient boosting machine (GBM), extreme gradient boosting (XGBoost), light gradient boosting machine (LightGBM) algorithms, and a stacked combination of these algorithms with a linear regression algorithm. The models relied on input variables that represent solar activity, geomagnetic activity, season, time of the day, interplanetary magnetic field, and solar wind. The models were trained using the VTEC data from January 2011 to December 2018, excluding the testing data. The testing data comprised the data for the year 2015 and the initial 6 months of 2017. The RandomizedSearchCV algorithm was used to determine the optimal hyperparameters of the models. The predicted VTEC values of the four ML models were strongly correlated with the GPS VTEC, with a correlation coefficient of ∼0.96, which is significantly higher than the corresponding value of the International Reference Ionosphere (IRI 2020) model, which is 0.87. Comparing the GPS VTEC values with the predicted VTEC values based on diurnal and seasonal characteristics showed that the predictions of the developed models were generally in good agreement and outperformed the IRI 2020 model. Overall, the ML models used in this study demonstrated promising potential for accurate single‐station VTEC prediction over Ethiopia.
Global Magnetic Reconnection During Sustained Sub‐Alfvénic Solar Wind Driving
Authors: Burkholder B. L. , Chen L.‐J. , Sarantos M. , Gershman D. J. , Argall M. R. , Chen Y. , Dong C. , Wilder F. D. , Le Contel O. , Gurram H.
Published: March 2024

When the solar wind speed falls below the local Alfvén speed, the magnetotail transforms into an Alfvén wing configuration. A Grid Agnostic Magnetohydrodynamics for Extended Research Applications (GAMERA) simulation of Earth's magnetosphere using solar wind parameters from the 24 April 2023 sub‐Alfvénic interval is examined to reveal modifications of Dungey‐type magnetotail reconnection during sustained sub‐Alfvénic solar wind. The simulation shows new magnetospheric flux is generated via reconnection between polar cap field lines from the northern and southern hemisphere, similar to Dungey‐type magnetotail reconnection between lobe field lines mapping to opposite hemispheres. The key feature setting the Alfvén wing reconnection apart from the typical Dungey‐type is that the majority of new magnetospheric flux is added to the polar cap at local times 1–3 (21‐23) in the northern (southern) hemisphere. During most of the sub‐Alfvénic interval, reconnection mapping to midnight in the polar cap generates relatively little new magnetospheric flux.
HMGA2 alleviates ferroptosis by promoting GPX4 expression in pancreatic cancer cells
Authors: Luo Ziyang , Zheng Qingfang , Ye Shazhou , Li Yanguo , Chen Jiayi , Fan Chengjiang , Chen Jianing , Lei Yuxin , Liao Qi , Xi Yang
Published: March 2024

Pancreatic cancer is one of the most malignant tumor types and is characterized by high metastasis ability and a low survival rate. As a chromatin-binding protein, HMGA2 is widely overexpressed and considered an oncogene with various undefined regulatory mechanisms. Herein, we demonstrated that HMGA2 is highly expressed in pancreatic cancer tissues, mainly distributed in epithelial cells, and represents a subtype of high epithelial–mesenchymal transition. Deletion of HMGA2 inhibits tumor malignancy through cell proliferation, metastasis, and xenograft tumor growth in vivo. Moreover, HMGA2 enhanced the cellular redox status by inhibiting reactive oxygen species and promoting glutathione production. Importantly, ferroptotic cell death was significantly ameliorated in cells overexpressing HMGA2. Conversely, HMGA2 deletion exacerbated ferroptosis. Mechanistically, HMGA2 activated GPX4 expression through transcriptional and translational regulation. HMGA2 binds and promotes cis-element modification in the promoter region of the GPX4 gene by enhancing enhancer activity through increased H3K4 methylation and H3K27 acetylation. Furthermore, HMGA2 stimulated GPX4 protein synthesis via the mTORC1-4EBP1 and -S6K signaling axes. The overexpression of HMGA2 alleviated the decrease in GPX4 protein levels resulting from the pharmacologic inhibition of mTORC1. Conversely, compared with the control, HMGA2 deletion more strongly reduced the phosphorylation of 4EBP1 and S6K. A strong positive correlation between HMGA2 and GPX4 expression was confirmed using immunohistochemical staining. We also demonstrated that HMGA2 mitigated the sensitivity of cancer cells to combination treatment with a ferroptosis inducer and mTORC1 inhibition or gemcitabine. In summary, our results revealed a regulatory mechanism by which HMGA2 coordinates GPX4 expression and underscores the potential value of targeting HMGA2 in cancer treatment.
HOXD3 promotes the migration and angiogenesis of hepatocellular carcinoma via modifying hepatocellular carcinoma cells exosome-delivered CCR6 and regulating chromatin conformation of CCL20
Authors: Wang Lumin , Qiao Chenyang , Han Lili , Wang Xiaofei , Miao Jiyu , Cao Li , Huang Chen , Wang Jinhai
Published: March 2024

Angiogenesis plays an essential role in the microenvironment of hepatocellular carcinoma (HCC). HOXD3 is involved in the metastasis and invasion of HCC cells; Whereas the underlying molecular mechanisms in the microenvironment of HCC remain unknown. Wound healing, transwell invasion, tube formation and spheroid sprouting assays were carried out to identify the effects of HCC-HOXD3-exosomes and genes on the migration of HCC cells. ChIP–PCR was applied to test the binding region of HOXD3 on CCR6, Med15, and CREBBP promoter. Exosome isolation and mRNA-seq were applied to examine the morphological characteristics of exosomes and the contained mRNA in exosomes. Co-IP and Immunofluorescence assays were used to demonstrate the role of CREBBP in the chromatin conformation of CCL20. The nude mice were used to identify the function of genes in regulating migration of HCC in vivo. In this study, integrated cellular and bioinformatic analyses revealed that HOXD3 targeted the promoter region of CCR6 and induced its transcription. CCR6 was delivered by exosomes to endothelial cells and promoted tumour migration. Overexpression of CCR6 promoted metastasis, invasion in HCCs and angiogenesis in endothelial cells (ECs), whereas its downregulation suppressed these functions. The role of HOXD3 in the metastasis and invasion of HCC cells was reversed after the suppression of CCR6. Furthermore, CCL20 was demonstrated as the ligand of CCR6, and its high expression was found in HCC tissues and cells, which was clinically associated with the poor prognosis of HCC. Mechanistically, HOXD3 targets the promoter regions of CREBBP and Med15, which affect CCL20 chromatin conformation by regulating histone acetylation and expression of Pol II to enhance the migration of HCCs. This study demonstrated the function of the HOXD3–CREBBP/Med15–CCL20–CCR6 axis in regulating invasion and migration in HCC, thus providing new therapeutic targets for HCC.
Theoretical formulation of chemical equilibrium under vibrational strong coupling
Authors: Sun Kaihong , Ribeiro Raphael F.
Published: March 2024

Experiments have suggested that strong interactions between molecular ensembles and infrared microcavities can be employed to control chemical equilibria. Nevertheless, the primary mechanism and key features of the effect remain largely unexplored. In this work, we develop a theory of chemical equilibrium in optical microcavities, which allows us to relate the equilibrium composition of a mixture in different electromagnetic environments. Our theory shows that in planar microcavities under strong coupling with polyatomic molecules, hybrid modes formed between all dipole-active vibrations and cavity resonances contribute to polariton-assisted chemical equilibrium shifts. To illustrate key aspects of our formalism, we explore a model SN2 reaction within a single-mode infrared resonator. Our findings reveal that chemical equilibria can be shifted towards either direction of a chemical reaction, depending on the oscillator strength and frequencies of reactant and product normal modes. Polariton-induced zero-point energy changes provide the dominant contributions, though the effects in idealized single-mode cavities tend to diminish quickly as the temperature and number of molecules increase. Our approach is valid in generic electromagnetic environments and paves the way for understanding and controlling chemical equilibria with microcavities.
Assessing intra- and inter-molecular charge transfer excitations in non-fullerene acceptors using electroabsorption spectroscopy
Authors: Mahadevan Sudhi , Liu Taili , Pratik Saied Md , Li Yuhao , Ho Hang Yuen , Ouyang Shanchao , Lu Xinhui , Yip Hin-Lap , Chow Philip C. Y. , Brédas Jean-Luc , Coropceanu Veaceslav , So Shu Kong , Tsang Sai-Wing
Published: March 2024

Organic photovoltaic cells using Y6 non-fullerene acceptors have recently achieved high efficiency, and it was suggested to be attributed to the charge-transfer (CT) nature of the excitations in Y6 aggregates. Here, by combining electroabsorption spectroscopy measurements and electronic-structure calculations, we find that the charge-transfer character already exists in isolated Y6 molecules but is strongly increased when there is molecular aggregation. Surprisingly, it is found that the large enhanced charge transfer in clustered Y6 molecules is not due to an increase in excited-state dipole moment, Δμ, as observed in other organic systems, but due to a reduced polarizability change, Δp. It is proposed that such a strong charge-transfer character is promoted by the stabilization of the charge-transfer energy upon aggregation, as deduced from density functional theory and four-state model calculations. This work provides insight into the correlation between molecular electronic properties and charge-transfer characteristics in organic electronic materials.
Hermitian and non-Hermitian topology from photon-mediated interactions
Authors: Roccati Federico , Bello Miguel , Gong Zongping , Ueda Masahito , Ciccarello Francesco , Chenu Aurélia , Carollo Angelo
Published: March 2024

As light can mediate interactions between atoms in a photonic environment, engineering it for endowing the photon-mediated Hamiltonian with desired features, like robustness against disorder, is crucial in quantum research. We provide general theorems on the topology of photon-mediated interactions in terms of both Hermitian and non-Hermitian topological invariants, unveiling the phenomena of topological preservation and reversal, and revealing a system-bath topological correspondence. Depending on the Hermiticity of the environment and the parity of the spatial dimension, the atomic and photonic topological invariants turn out to be equal or opposite. Consequently, the emergence of atomic and photonic topological boundary modes with opposite group velocities in two-dimensional Hermitian topological systems is established. Owing to its general applicability, our results can guide the design of topological systems.
Ultrasound-induced reorientation for multi-angle optical coherence tomography
Authors: Kvåle Løvmo Mia , Deng Shiyu , Moser Simon , Leitgeb Rainer , Drexler Wolfgang , Ritsch-Marte Monika
Published: March 2024

Organoid and spheroid technology provide valuable insights into developmental biology and oncology. Optical coherence tomography (OCT) is a label-free technique that has emerged as an excellent tool for monitoring the structure and function of these samples. However, mature organoids are often too opaque for OCT. Access to multi-angle views is highly desirable to overcome this limitation, preferably with non-contact sample handling. To fulfil these requirements, we present an ultrasound-induced reorientation method for multi-angle-OCT, which employs a 3D-printed acoustic trap inserted into an OCT imaging system, to levitate and reorient zebrafish larvae and tumor spheroids in a controlled and reproducible manner. A model-based algorithm was developed for the physically consistent fusion of multi-angle data from a priori unknown angles. We demonstrate enhanced penetration depth in the joint 3D-recovery of reflectivity, attenuation, refractive index, and position registration for zebrafish larvae, creating an enabling tool for future applications in volumetric imaging.
Genomic malaria surveillance of antenatal care users detects reduced transmission following elimination interventions in Mozambique
Authors: Brokhattingen Nanna , Matambisso Glória , da Silva Clemente , Neubauer Vickers Eric , Pujol Arnau , Mbeve Henriques , Cisteró Pau , Maculuve Sónia , Cuna Boaventura , Melembe Cardoso , Ndimande Nelo , Palmer Brian , García-Ulloa Manuel , Munguambe Humberto , Montaña-Lopez Júlia , Nhamussua Lidia , Simone Wilson , Chidimatembue Arlindo , Galatas Beatriz , Guinovart Caterina , Rovira-Vallbona Eduard , Saúte Francisco , Aide Pedro , Aranda-Díaz Andrés , Greenhouse Bryan , Macete Eusébio , Mayor Alfredo
Published: March 2024

Routine sampling of pregnant women at first antenatal care (ANC) visits could make Plasmodium falciparum genomic surveillance more cost-efficient and convenient in sub-Saharan Africa. We compare the genetic structure of parasite populations sampled from 289 first ANC users and 93 children from the community in Mozambique between 2015 and 2019. Samples are amplicon sequenced targeting 165 microhaplotypes and 15 drug resistance genes. Metrics of genetic diversity and relatedness, as well as the prevalence of drug resistance markers, are consistent between the two populations. In an area targeted for elimination, intra-host genetic diversity declines in both populations (p = 0.002-0.007), while for the ANC population, population genetic diversity is also lower (p = 0.0004), and genetic relatedness between infections is higher (p = 0.002) than control areas, indicating a recent reduction in the parasite population size. These results highlight the added value of genomic surveillance at ANC clinics to inform about changes in transmission beyond epidemiological data.
Axl and MerTK regulate synovial inflammation and are modulated by IL-6 inhibition in rheumatoid arthritis
Authors: Nerviani Alessandra , Boutet Marie-Astrid , Ghirardi Giulia Maria , Goldmann Katriona , Sciacca Elisabetta , Rivellese Felice , Pontarini Elena , Prediletto Edoardo , Abatecola Federico , Caliste Mattia , Pagani Sara , Mauro Daniele , Bellan Mattia , Cubuk Cankut , Lau Rachel , Church Sarah E. , Hudson Briana M. , Humby Frances , Bombardieri Michele , Lewis Myles J. , Pitzalis Costantino
Published: March 2024

The TAM tyrosine kinases, Axl and MerTK, play an important role in rheumatoid arthritis (RA). Here, using a unique synovial tissue bioresource of patients with RA matched for disease stage and treatment exposure, we assessed how Axl and MerTK relate to synovial histopathology and disease activity, and their topographical expression and longitudinal modulation by targeted treatments. We show that in treatment-naive patients, high AXL levels are associated with pauci-immune histology and low disease activity and inversely correlate with the expression levels of pro-inflammatory genes. We define the location of Axl/MerTK in rheumatoid synovium using immunohistochemistry/fluorescence and digital spatial profiling and show that Axl is preferentially expressed in the lining layer. Moreover, its ectodomain, released in the synovial fluid, is associated with synovial histopathology. We also show that Toll-like-receptor 4-stimulated synovial fibroblasts from patients with RA modulate MerTK shedding by macrophages. Lastly, Axl/MerTK synovial expression is influenced by disease stage and therapeutic intervention, notably by IL-6 inhibition. These findings suggest that Axl/MerTK are a dynamic axis modulated by synovial cellular features, disease stage and treatment.
Structural and mechanistic insights into activation of the human RNA ligase RTCB by Archease
Authors: Gerber Janina Lara , Morales Guzmán Suria Itzel , Worf Lorenz , Hubbe Petra , Kopp Jürgen , Peschek Jirka
Published: March 2024

RNA ligases of the RTCB-type play an essential role in tRNA splicing, the unfolded protein response and RNA repair. RTCB is the catalytic subunit of the pentameric human tRNA ligase complex. RNA ligation by the tRNA ligase complex requires GTP-dependent activation of RTCB. This active site guanylylation reaction relies on the activation factor Archease. The mechanistic interplay between both proteins has remained unknown. Here, we report a biochemical and structural analysis of the human RTCB-Archease complex in the pre- and post-activation state. Archease reaches into the active site of RTCB and promotes the formation of a covalent RTCB-GMP intermediate through coordination of GTP and metal ions. During the activation reaction, Archease prevents futile RNA substrate binding to RTCB. Moreover, monomer structures of Archease and RTCB reveal additional states within the RNA ligation mechanism. Taken together, we present structural snapshots along the reaction cycle of the human tRNA ligase.
Therapeutic targeting nudix hydrolase 1 creates a MYC-driven metabolic vulnerability
Authors: Ye Minhui , Fang Yingzhe , Chen Lu , Song Zemin , Bao Qing , Wang Fei , Huang Hao , Xu Jin , Wang Ziwen , Xiao Ruijing , Han Meng , Gao Song , Liu Hudan , Jiang Baishan , Qing Guoliang
Published: March 2024

Tumor cells must rewire nucleotide synthesis to satisfy the demands of unbridled proliferation. Meanwhile, they exhibit augmented reactive oxygen species (ROS) production which paradoxically damages DNA and free deoxy-ribonucleoside triphosphates (dNTPs). How these metabolic processes are integrated to fuel tumorigenesis remains to be investigated. MYC family oncoproteins coordinate nucleotide synthesis and ROS generation to drive the development of numerous cancers. We herein perform a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based functional screen targeting metabolic genes and identified nudix hydrolase 1 (NUDT1) as a MYC-driven dependency. Mechanistically, MYC orchestrates the balance of two metabolic pathways that act in parallel, the NADPH oxidase 4 (NOX4)-ROS pathway and the Polo like kinase 1 (PLK1)-NUDT1 nucleotide-sanitizing pathway. We describe LC-1-40 as a potent, on-target degrader that depletes NUDT1 in vivo. Administration of LC-1-40 elicits excessive nucleotide oxidation, cytotoxicity and therapeutic responses in patient-derived xenografts. Thus, pharmacological targeting of NUDT1 represents an actionable MYC-driven metabolic liability.
A universal system for boosting gene expression in eukaryotic cell-lines
Authors: Vaknin Inbal , Willinger Or , Mandl Jonathan , Heuberger Hadar , Ben-Ami Dan , Zeng Yi , Goldberg Sarah , Orenstein Yaron , Amit Roee
Published: March 2024

We demonstrate a transcriptional regulatory design algorithm that can boost expression in yeast and mammalian cell lines. The system consists of a simplified transcriptional architecture composed of a minimal core promoter and a synthetic upstream regulatory region (sURS) composed of up to three motifs selected from a list of 41 motifs conserved in the eukaryotic lineage. The sURS system was first characterized using an oligo-library containing 189,990 variants. We validate the resultant expression model using a set of 43 unseen sURS designs. The validation sURS experiments indicate that a generic set of grammar rules for boosting and attenuation may exist in yeast cells. Finally, we demonstrate that this generic set of grammar rules functions similarly in mammalian CHO-K1 and HeLa cells. Consequently, our work provides a design algorithm for boosting the expression of promoters used for expressing industrially relevant proteins in yeast and mammalian cell lines.
Maternal dietary fat during lactation shapes single nucleus transcriptomic profile of postnatal offspring hypothalamus in a sexually dimorphic manner in mice
Authors: Huang Yi , Wang Anyongqi , Zhou Wenjiang , Li Baoguo , Zhang Linshan , Rudolf Agata M. , Jin Zengguang , Hambly Catherine , Wang Guanlin , Speakman John R.
Published: March 2024

Maternal overnutrition during lactation predisposes offspring to develop metabolic diseases and exacerbates the relevant syndromes in males more than females in later life. The hypothalamus is a heterogenous brain region that regulates energy balance. Here we combined metabolic trait quantification of mother and offspring mice under low and high fat diet (HFD) feeding during lactation, with single nucleus transcriptomic profiling of their offspring hypothalamus at peak lacation to understand the cellular and molecular alterations in response to maternal dietary pertubation. We found significant expansion in neuronal subpopulations including histaminergic (Hdc), arginine vasopressin/retinoic acid receptor-related orphan receptor β (Avp/Rorb) and agouti-related peptide/neuropeptide Y (AgRP/Npy) in male offspring when their mothers were fed HFD, and increased Npy-astrocyte interactions in offspring responding to maternal overnutrition. Our study provides a comprehensive offspring hypothalamus map at the peak lactation and reveals how the cellular subpopulations respond to maternal dietary fat in a sex-specific manner during development.
SpyMask enables combinatorial assembly of bispecific binders
Authors: Driscoll Claudia L. , Keeble Anthony H. , Howarth Mark R.
Published: March 2024

Bispecific antibodies are a successful and expanding therapeutic class. Standard approaches to generate bispecifics are complicated by the need for disulfide reduction/oxidation or specialized formats. Here we present SpyMask, a modular approach to bispecifics using SpyTag/SpyCatcher spontaneous amidation. Two SpyTag-fused antigen-binding modules can be precisely conjugated onto DoubleCatcher, a tandem SpyCatcher where the second SpyCatcher is protease-activatable. We engineer a panel of structurally-distinct DoubleCatchers, from which binders project in different directions. We establish a generalized methodology for one-pot assembly and purification of bispecifics in 96-well plates. A panel of binders recognizing different HER2 epitopes were coupled to DoubleCatcher, revealing unexpected combinations with anti-proliferative or pro-proliferative activity on HER2-addicted cancer cells. Bispecific activity depended sensitively on both binder orientation and DoubleCatcher scaffold geometry. These findings support the need for straightforward assembly in different formats. SpyMask provides a scalable tool to discover synergy in bispecific activity, through modulating receptor organization and geometry.
Long noncoding RNA Malat1 protects against osteoporosis and bone metastasis
Authors: Zhao Yang , Ning Jingyuan , Teng Hongqi , Deng Yalan , Sheldon Marisela , Shi Lei , Martinez Consuelo , Zhang Jie , Tian Annie , Sun Yutong , Nakagawa Shinichi , Yao Fan , Wang Hai , Ma Li
Published: March 2024

MALAT1, one of the few highly conserved nuclear long noncoding RNAs (lncRNAs), is abundantly expressed in normal tissues. Previously, targeted inactivation and genetic rescue experiments identified MALAT1 as a suppressor of breast cancer lung metastasis. On the other hand, Malat1-knockout mice are viable and develop normally. On a quest to discover the fundamental roles of MALAT1 in physiological and pathological processes, we find that this lncRNA is downregulated during osteoclastogenesis in humans and mice. Remarkably, Malat1 deficiency in mice promotes osteoporosis and bone metastasis of melanoma and mammary tumor cells, which can be rescued by genetic add-back of Malat1. Mechanistically, Malat1 binds to Tead3 protein, a macrophage-osteoclast–specific Tead family member, blocking Tead3 from binding and activating Nfatc1, a master regulator of osteoclastogenesis, which results in the inhibition of Nfatc1-mediated gene transcription and osteoclast differentiation. Notably, single-cell transcriptome analysis of clinical bone samples reveals that reduced MALAT1 expression in pre-osteoclasts and osteoclasts is associated with osteoporosis and metastatic bone lesions. Altogether, these findings identify Malat1 as a lncRNA that protects against osteoporosis and bone metastasis.
Three-dimensional ultrafast charge-density-wave dynamics in CuTe
Authors: Nhat Quyen Nguyen , Tzeng Wen-Yen , Hsu Chih-En , Lin I-An , Chen Wan-Hsin , Jia Hao-Hsiang , Wang Sheng-Chiao , Liu Cheng-En , Chen Yu-Sheng , Chen Wei-Liang , Chou Ta-Lei , Wang I-Ta , Kuo Chia-Nung , Lin Chun-Liang , Wu Chien-Te , Lin Ping-Hui , Weng Shih-Chang , Cheng Cheng-Maw , Kuo Chang-Yang , Tu Chien-Ming , Chu Ming-Wen , Chang Yu-Ming , Lue Chin Shan , Hsueh Hung-Chung , Luo Chih-Wei
Published: March 2024

Charge density waves (CDWs) involved with electronic and phononic subsystems simultaneously are a common quantum state in solid-state physics, especially in low-dimensional materials. However, CDW phase dynamics in various dimensions are yet to be studied, and their phase transition mechanism is currently moot. Here we show that using the distinct temperature evolution of orientation-dependent ultrafast electron and phonon dynamics, different dimensional CDW phases are verified in CuTe. When the temperature decreases, the shrinking of c-axis length accompanied with the appearance of interchain and interlayer interactions causes the quantum fluctuations (QF) of the CDW phase until 220 K. At T < 220 K, the CDWs on the different ab-planes are finally locked with each other in anti-phase to form a CDW phase along the c-axis. This study shows the dimension evolution of CDW phases in one CDW system and their stabilized mechanisms in different temperature regimes.