bluuebunny/crossref_metadata_2025 huggingface dataset:
Soyasaponin Bb has poor absorption and bioavailability in Sprague–Dawley rats and Caco-2 intestinal epithelial cell model
Authors: Xiao Lingyu , Su Chuhong , Chen Junbin , Gu Xiangfu , Zhao Yue , Tang Jiaqi , Liu Yuguo , Luo Huiyu , Zha Longying
Published: February 2025

Soyasaponin Bb has various health-promoting bioactivities. However, the bioavailability of soyasaponin Bb is not fully understood. This study aimed to explore the absorption and metabolism of soyasaponin Bb by using both in vivo and in vitro methods. Soyasaponin Bb (100 mg/kg) was orally administrated in Sprague–Dawley (SD) rats, and the content of soyasaponin Bb and soyasapogenol B in plasma, urine and feces were determined by HPLC–MS/MS. The Caco-2 intestinal epithelial cell model was established by culturing on Transwell plates and assessing through cell morphology, transepithelial electrical resistance, alkaline phosphatase activity, and phenol red flux. Then, the apical (AP) to basolateral (BL) transport or uptake of soyasaponin Bb in the model were determined. In SD rats, soyasaponin Bb reached a maximum of 19.8 ng/mL in plasma and showed two material peaks. The cumulative excretion of soyasaponin Bb at 168 h was (0.0022 ± 0.0006) % in urine and (0.36 ± 0.21) % in feces. Soyasapogenol B was not detected in plasma and urine, but had a cumulative excretion of (0.45 ± 0.29) % in feces at 168 h. Culturing Caco-2 cells on Transwell plates for 21 days formed good intestinal epithelial monolayers. The apparent permeability (Papp) of both AP-BL and BL-AP transport of soyasaponin Bb in the Caco-2 cell models was less than 1.0 × 10–6 cm/s, and the efflux ratio (ER) was 0.5 ± 0.2. The uptake of soyasaponin Bb in the AP-BL cells was significantly higher (p < 0.05) than that in the BL-AP cells. In conclusion, soyasaponin Bb has poor absorption and bioavailability in SD rats and Caco-2 intestinal epithelial cell model.
Combined Use of Pan-Immune-Inflammation Value and Triglyceride-Glucose Index for Risk Prediction of Contrast-Induced Nephropathy After Coronary Angiography in Patients with STEMI
Authors: Zorlu Çağrı , Cabri Gökhan , Şimşek Ahmet , Demirezen Yağmur , Ömür Sefa Erdi
Published: February 2025

Aim

The pan-immune-inflammation value (PIV) and triglyceride-glucose (TyG) index are very important parameters that predict contrast-induced nephropathy (CIN) well in patients with ST-elevation myocardial infarction (STEMI) underwent percutaneous coronary intervention (PCI). There are limited data on the predictive value of CIN derived from the combination of PIV and TyG index compared to the use of PIV and CIN alone in patients with STEMI who underwent PCI. We aimed to evaluate the ability of the combination of PIV and TyG index, routinely obtained on admission, to identify STEMI patients at risk of CIN.

Method

Between 2018 and 2024, 2367 patients with STEMI who underwent PCI were included. CIN was defined as a 25% or 0.5 mg/dL increase in creatinine from baseline within 48–72 h after PCI. Receiver operating curve (ROC) analysis was performed to predict the development of CIN.

Results

In ROC analysis, the cut-off values of PIV and TyG index for best predicting CIN were 548, and 8.97 respectively. The combination of two markers was the most powerful predictor of CIN risk when included in a single variable such as high PIV or high TyG index. Furthermore, the co-presence of high PIV and high TyG index exhibited the highest specificity for CIN(82%) compared to high PIV(77%) or TyG index(71%) alone.

Conclusion

The combination of PIV and TyG index, a simple and cost-effective risk assessment, may be a more reliable prognostic indicator for predicting the development of CIN in STEMI patients undergoing PCI than the use of PIV and TyG index alone.
A morphological and molecular study of adults and cystacanths of Oncicola luehei Travassos, 1917 (Acanthocephala: Archiacanthocephala), from the Neotropical region of Mexico
Authors: Sereno-Uribe A.L. , Ortega-Olivares M.P. , González-García M.T. , Grano-Maldonado M.I. , García-Varela M.
Published: February 2025

Members of the genus Oncicola Travassos, 1916 are generalist parasites able to infect a broad spectrum of carnivorous hosts, such as marsupials, procyonids, felids, and canids, and are distributed globally. Adult specimens were collected from the intestines of three white-nosed coatis (N. narica), whereas cystacanths (larval form) were found in the body cavities of two amphibian species (paratenic hosts) in localities from northern and southeastern Mexico. Morphologically, both stages were identified as O. luehei (Travassos, 1917) on the basis of the following features: trunk cylindrical, narrow anteriorly, enlarging midbody, tapering gradually to narrow posteriorly; proboscis globular with six circular rows of hooks with six hooks each, decreasing in size posteriorly; neck short with sensory papilla; tubular lemnisci long, extending to the posterior region; protonephridia dendritic type; and eight cement glands, compact with a single giant nuclei. Sequences from cytochrome c oxidase subunit 1 from mtDNA were aligned and compared with sequences available in GenBank. Phylogenetic analyses revealed that adults and cystacanths formed a clade with two other isolates identified as Oncicola sp. and O. luehei from Mexico. The intraspecific genetic divergence among the isolates was low, ranging from 0.0% to 3.0%, indicating that the two stages of the life cycle belong to the same species. The haplotype network was inferred with 11 sequences and revealed a lack of shared haplotypes between populations, suggesting a reduced recombination rate and a high pattern of genetic variation among individuals. Finally, these new records of O. luehei increase the distribution range of O. luehei on both coasts of Mexico.
A new species of Armandia and a new record of Ophelina (Polychaeta: Opheliidae) from Indian waters
Authors: Gopal Aiswarya , Sivadas Sanitha K. , Ramu Karri
Published: February 2025

A new species of polychaete annelid, Armandia ramanamurthyi n. sp., is described from the sandy sediments off Tamil Nadu coast, Bay of Bengal, northern Indian Ocean. The major feature distinguishing A. ramanamurthyi n. sp. from other species of the genus is bearing a non-papillated anal tube and the presence of a bulbous, orbicular papilla ventrally placed at the proximal end of the anal tube. The orbicular papilla bears black pigmentation and posteriorly ends in an oblique cirrus. Additionally, Ophelina arabica Parapar, Al-Kandari, Barroso & Moreira, 2023 described from Kuwait waters is recorded for the first time in Indian waters since its original description.
Deconstructing the nature of emotion regulation impairments at the identification, selection, and implementation stages in individuals at clinical high-risk for psychosis
Authors: Strauss Gregory P. , Raugh Ian , Visser Katherine , Walker Elaine , Mittal Vijay
Published: February 2025

Background

Psychotic disorders are characterized by emotion regulation abnormalities that predict greater symptom severity and poor functional outcomes. However, it is unclear whether these abnormalities also occur in individuals at clinically high risk for psychosis (CHR). The current study used ecological momentary assessment (EMA) to address this question and examined the nature of abnormalities at three stages of emotion regulation (identification, selection, implementation).

Methods

Participants included 120 CHR and 59 CN who completed 1 week of EMA surveys evaluating emotional experience, emotion regulation, context, and symptoms. Multi-level models examined concurrent and time-lagged effects.

Results

CHR evidenced elevated state negative affect and abnormalities at all three stages of emotion regulation. At the identification stage (i.e., determining the need to regulate), regulatory attempts were made too frequently and with too much effort at low levels of negative affect and not frequently enough and with insufficient effort at high levels of negative affect. Selection stage abnormalities (i.e., choosing the exact strategy to attempt based on context) were characterized by increased frequency of selecting individual strategies and greater polyregulation (i.e., use of multiple strategies concurrently). Implementation stage (i.e., executing the selected strategy) abnormalities were indicated by being less effective at decreasing the intensity of negative affect from time t to t + 1.

Conclusions

It is not only heightened stress reactivity that confers risk for psychosis, but also abnormalities in applying emotion regulation strategies to control the stress response. The profile of abnormalities observed in CHR is similar to schizophrenia, suggesting treatment targets that transcend phases of psychotic illness.
Disrupted functional connectivity of the emotion regulation network in major depressive disorder and its association with symptom improvement: A multisite resting-state functional MRI study
Authors: Lan Zhihui , Zhu Lin-lin , Dai You-ran , Wu Yan-kun , Shen Tian , Yang Jing-jing , Li Ji-tao , Xia Mingrui , Wang Xiaoqin , Wei Dongtao , Liu Bangshan , Chen Taolin , Tang Yanqing , Gong Qiyong , Wang Fei , Qiu Jiang , Xie Peng , Li Lingjiang , He Yong , Su Yun-Ai ,   DIDA-MDD Working Group, Si Tianmei
Published: February 2025

Background

The emotion regulation network (ERN) in the brain provides a framework for understanding the neuropathology of affective disorders. Although previous neuroimaging studies have investigated the neurobiological correlates of the ERN in major depressive disorder (MDD), whether patients with MDD exhibit abnormal functional connectivity (FC) patterns in the ERN and whether the abnormal FC in the ERN can serve as a therapeutic response signature remain unclear.

Methods

A large functional magnetic resonance imaging dataset comprising 709 patients with MDD and 725 healthy controls (HCs) recruited across five sites was analyzed. Using a seed-based FC approach, we first investigated the group differences in whole-brain resting-state FC of the 14 ERN seeds between participants with and without MDD. Furthermore, an independent sample (45 MDD patients) was used to evaluate the relationship between the aforementioned abnormal FC in the ERN and symptom improvement after 8 weeks of antidepressant monotherapy.

Results

Compared to the HCs, patients with MDD exhibited aberrant FC between 7 ERN seeds and several cortical and subcortical areas, including the bilateral middle temporal gyrus, bilateral occipital gyrus, right thalamus, calcarine cortex, middle frontal gyrus, and the bilateral superior temporal gyrus. In an independent sample, these aberrant FCs in the ERN were negatively correlated with the reduction rate of the HAMD17 score among MDD patients.

Conclusions

These results might extend our understanding of the neurobiological underpinnings underlying unadaptable or inflexible emotional processing in MDD patients and help to elucidate the mechanisms of therapeutic response.
Cognitive presentation at psychosis onset through premorbid deterioration and exposure to environmental risk factors
Authors: Ferraro Laura , Di Forti Marta , La Barbera Daniele , La Cascia Caterina , Morgan Craig , Tripoli Giada , Jongsma Hannah , Seminerio Fabio , Sartorio Crocettarachele , Sideli Lucia , Tarricone Ilaria , Carloni Anna Lisa , Szoke Andrei , Pignon Baptiste , Bernardo Miguel , de Haan Lieuwe , Arango Celso , Velthorst Eva , Gayer-Anderson Charlotte , Kirkbride James , Rutten Bart P. F. , Lasalvia Antonio , Tosato Sarah , Del Ben Cristina Marta , Menezes Paulo Rossi , Bobes Julio , Arrojo Manuel , Tortelli Andrea , Jones Peter , Selten Jean-Paul , van Os Jim ,   The WP2 EU-GEI Group, Murray Robin , Quattrone Diego , Vassos Evangelos
Published: February 2025

Background

Previous studies identified clusters of first-episode psychosis (FEP) patients based on cognition and premorbid adjustment. This study examined a range of socio-environmental risk factors associated with clusters of FEP, aiming a) to compare clusters of FEP and community controls using the Maudsley Environmental Risk Score for psychosis (ERS), a weighted sum of the following risks: paternal age, childhood adversities, cannabis use, and ethnic minority membership; b) to explore the putative differences in specific environmental risk factors in distinguishing within patient clusters and from controls.

Methods

A univariable general linear model (GLS) compared the ERS between 1,263 community controls and clusters derived from 802 FEP patients, namely, low (n = 223) and high-cognitive-functioning (n = 205), intermediate (n = 224) and deteriorating (n = 150), from the EU-GEI study. A multivariable GLS compared clusters and controls by different exposures included in the ERS.

Results

The ERS was higher in all clusters compared to controls, mostly in the deteriorating (β=2.8, 95% CI 2.3 3.4, η2 = 0.049) and the low-cognitive-functioning cluster (β=2.4, 95% CI 1.9 2.8, η2 = 0.049) and distinguished them from the cluster with high-cognitive-functioning. The deteriorating cluster had higher cannabis exposure (meandifference = 0.48, 95% CI 0.49 0.91) than the intermediate having identical IQ, and more people from an ethnic minority (meandifference = 0.77, 95% CI 0.24 1.29) compared to the high-cognitive-functioning cluster.

Conclusions

High exposure to environmental risk factors might result in cognitive impairment and lower-than-expected functioning in individuals at the onset of psychosis. Some patients’ trajectories involved risk factors that could be modified by tailored interventions.
“Our Own and Our Country’s Ruin”: Public Credit, War Markets, and Political Transition in the Colonial American Northeast, 1758–1768
Authors: Fifield Donovan
Published: February 2025

In British North America, imperial sovereignty required peripheral cooperation in public finance. However, because of limited coercive British state capacity, local colonial assemblies and town governments operated with substantial autonomy. The interests of colonial subjects did not align exactly with those of politicians and military officers in the center of British imperial authority in London. Short term success in colonial war between 1754 and 1763 required policies that incentivized colonists to buy into the imperial project. After 1758, Parliament and royal departments managed to incentivize greater provincial participation and resource allocation to the military by co-opting existing colonial merchant networks using lucrative public contracts. The contracts requested a small number of merchant firms in colonial cities take on large debts to circulate notes of credit in exchange for commissions. Merchant financiers could use these notes to pay for military expenses. The contracts promised bullion remittances from England to cover the debts, but these funds ultimately proved insufficient to cover outstanding obligations. Failures to remit led to a colonial credit crisis between 1762 and 1768 which shook colonists’ faith in the credibility of the British fiscal state in the decade leading up to the American Revolution.
Long‐Term Trend and Seasonal Cycles of Gap‐Free Downscaled Diurnal/Nocturnal LST and the Interaction to Functional Plant Trait Under Tropical Monsoon Climate
Authors: Hoa Pham Viet , Binh Nguyen An , Thao Giang Thi Phuong , An Nguyen Ngoc , Trinh Pham The , Tuan Nguyen Quang , Hanh Nguyen Cao
Published: February 2025

Land surface temperature (LST) monitoring via Earth observation constellation will become optimized and consistent with spatiotemporal‐explicit characteristics. Besides, scientific evidence for the interaction between LST and vegetation biophysical variables remains limited through spatial large‐scale assessment and seamless long‐term tracking. This study addresses this gap by utilizing gap‐filled fine spatial resolution LST products in understanding the dynamic over the period 2000–2023 and the spatiotemporal relationship with leaf area index (LAI). Firstly, Moderate Resolution Imaging Spectroradiometer (MODIS) LST 1,000 m of both daytime and nighttime were downscaled to a finer resolution of 250 m using the Random Forest algorithm. The Whittaker algorithm was then applied to obtain gap‐free LST products due to the typical cloud cover under tropical monsoon climate. Time series decomposition of gap‐filled fine resolution LST revealed slight warming trends in daytime (0.005°C year−1), nighttime (0.036°C year−1), and mean of all‐day time (0.02°C year−1) over recent 24 years, while seasonal amplitude in daytime (−3.7°C–4.8°C) is more fluctuated than in nighttime (−2.5°C–1.9°C). Spatial correlations of monthly LSTs and LAI indicated a consistent negative correlation (R ranging from −0.717 to −0.45). These findings shed light on the quantitative relationship between vegetation LAI and LST, contributing to a more unified theoretical framework for understanding functional vegetation responses under diverse climatic conditions.
Radiation Belt Losses: The Long‐Standing Debate Part II
Authors: Blum L. W. , Staples F. , Drozdov A. Y. , Michael A. , Millan R. , Tu W. , Zhao H. , Ukhorskiy A. , Fu X.
Published: February 2025

On 21 June 2022, during the annual Geospace Environment Modeling (GEM) workshop, a panel discussion titled “Radiation Belt Loss: The Long‐Standing Debate Part II” was organized by the focus group “System Understanding of Radiation Belt Particle Dynamics.” The panel focused on unresolved questions regarding the mechanisms driving electron loss in Earth's radiation belts, discussing topics including magnetopause shadowing, outward radial transport, and wave‐particle interactions driving particle precipitation. In this commentary, we provide an overview of the outcomes of this discussion and highlight future needs to better resolve outstanding questions.
A Potential Mushy Source for the Geysers of Enceladus and Other Icy Satellites
Authors: Meyer Colin R. , Buffo Jacob J. , Nimmo Francis , Wells Andrew J. , Boury Samuel , Fox‐Powell Mark , Tomlinson Tara C. , Parkinson Jamie R. G. , Vasil Geoffrey M.
Published: February 2025

Enceladus is a target for astrobiology due to the plume ejecta measured by the Cassini spacecraft and the inferred subsurface ocean that could be the source of the geysers. Here we explore an alternative where shear heating along tiger stripe fractures produces partial melting in the ice shell and interstitial convection allows fluid to be ejected as geysers. We use an idealized two‐dimensional reactive transport model to simulate a mushy region generated by an upper‐bound estimate for the localized shear heating rate. We find that the rate of internal melting could potentially match the observed eruption rate. The composition of the liquid brine would be, however, distinct from that of the ocean, due to fractionation during partial melting. This shear heating mechanism for geyser formation could apply to Enceladus and other icy moons and has implications for our understanding of the geophysical processes and astrobiological potential of icy satellites.
Transport of Nitric Oxide in the Winter Mesosphere and Lower Thermosphere
Authors: Liu H.‐L.
Published: February 2025

Nitric oxide (NO) plays key roles both in thermospheric energetics and upper‐lower atmosphere coupling. However, mesospheric NO in the polar night region has often been underestimated in whole atmosphere models, and the exact causes are not well understood. Recent high‐resolution (HR) WACCM‐X simulations show significant increase in NO in the polar night, and our analysis reveals distinct differences in the vertical transport between the HR and coarse resolution (CR) simulations: The residual mean vertical wind in the mesosphere and lower thermosphere (MLT) region displays mesoscale flow channels that are strong and alternate between upward and downward directions in the former, with large net downward transport over the polar region. In the latter it is much weaker and even upward over large latitude ranges. Moreover, the resolved waves in the HR simulations induce downward eddy transport of NO in the MLT much stronger than the parameterized diffusion in CR simulations.
Feedbacks Between Fjord Circulation, Mélange Melt, and the Subglacial Discharge Plume at Kangerlussuaq Glacier, East Greenland
Authors: Wood M. , Fenty I. , Khazendar A. , Willis J. K.
Published: February 2025

In recent decades, the Greenland ice sheet has been losing ice and contributing substantially to global sea level rise. Approximately half of this recent loss is due to glacier acceleration, increasing the calving of icebergs into the ocean. This process has been linked with increased ocean heat content on the continental shelf, yet the pathways delivering this heat into Greenland's fjords and its interactions with fjord‐scale processes modulating glacier ice loss are still unclear. In this study, we use a series of numerical ocean model configurations to examine feedbacks between ocean circulation, subglacial discharge, submarine glacier melt, and ice mélange in Kangerlussuaq Fjord—a major fjord system where Greenland's third‐largest glacier terminates. We find that subglacial discharge is a major control on ocean properties, increasing the up‐fjord advection of deep warm water more than 10‐fold over fjords without discharge and modulating ocean temperature on the continental shelf near the fjord mouth. Further, discharge‐driven upwelling increases ice mélange melt 3‐fold, revealing that subglacial discharge is an important control on mélange melt, particularly in the summer when submarine glacier melt and subsequent glacier retreat is highest. These results suggest that subglacial plume activity contributes to the strong correlation between mélange thickness and retreat noted in previous studies and may contribute to extensive future retreat at Kangerlussuaq Glacier.
Enhanced Sea Surface Cooling and Suppressed Storm Intensification During Slow‐Moving Track‐Turning Stage of Tropical Cyclones
Authors: Guan Shoude , Liu Ping , Zhang Yihan , Lin I.‐I. , Zhou Lei , Yang Qingxuan , Zhao Wei , Tian Jiwei
Published: February 2025

Tropical cyclones (TCs) often undergo track turning when moving over the ocean. However, the influence of track turning on TC‐ocean interactions remains little explored. This study systematically investigates sea surface temperature (SST) cooling and TC intensification during TC track‐turning stages in global TC‐active basins during 1998–2022. Globally, turning TCs induce stronger SST cooling than straight‐moving TCs (e.g., −1.53°C vs. −1.08°C for categories 1–2), expand cooling area by 40%–110%, and greatly reduce cooling asymmetry for left‐turning (right‐turning) TCs in the Northern (Southern) Hemisphere. The translation speed of turning TCs is 1.5 m s−1 slower compared to straight‐moving TCs. Numerical experiments demonstrate that the enhanced cooling is attributed to the combined effect of track turning and accompanying slow translation speed. The enhanced cooling effectively suppresses storm intensification of turning TCs. The intensification rate for straight‐moving versus turning TCs is 2.98 versus 0.06 m s−1 per 24 hr for categories 1–2. As turning angle increases, cooling magnitude increases and intensification rate decreases. The probability of rapid intensification for turning TCs is about one‐third lower than that for straight‐moving TCs. Consequently, TCs with smaller turning angles are more likely to develop into intense TCs. Operational forecast models underforecast turning angles of turning TCs and thus overforecast TC intensity with forecast errors increasing with turning angle. This study demonstrates that TC track‐turning stages play a crucial role in modulating TC intensification via an oceanic pathway, highlighting that improving track turning forecast will contribute to enhancing TC intensity forecast accuracy.
Experimental Soil Warming Impacts Soil Moisture and Plant Water Stress and Thereby Ecosystem Carbon Dynamics
Authors: Riley W. J. , Tao J. , Mekonnen Z. A. , Grant R. F. , Brodie E. L. , Pegoraro E. , Torn M. S.
Published: February 2025

Experimental soil heating experiments have found a consistent increase in soil‐surface CO2 emissions (Fs), but inconsistent soil organic carbon (SOC) responses. Interpretation of heating effects is complicated by spatial heterogeneity and soil moisture, nitrogen availability, and microbial and plant responses. Here we applied a mechanistic ecosystem model to interpret heating impacts on a California forest subjected to 1 m deep, 4°C heating. The model accurately simulated control‐plot CO2 fluxes, SOC stocks, fine root biomass, soil moisture, and soil temperature, and the observed increases in Fs and decreases in fine root biomass. We show that a complex suite of interactions can lead to a consistent increase in Fs (∼17%) over the 5‐year study period, with very small changes in SOC stocks (<1%). Modeled increases in leaf water stress from soil drying reduced GPP and NPP. The resulting reduction in leaf and fine root allocation increased fine root litter inputs to the soil and reduced root exudation. Soil heating led to about a 50% larger increase in root autotrophic respiration than in heterotrophic respiration, with the heating effect on both these fluxes decreasing over the simulation period. Increased heterotrophic respiration led to increased soil N availability and plant N uptake. These heating responses are mechanistically linked, of magnitudes that can affect ecosystem dynamics, and long‐term observations of them are rarely made. Therefore, we conclude that a coupled observational and mechanistic modeling framework is needed to interpret manipulation experiments, and to improve projections of climate change impacts on terrestrial ecosystem carbon dynamics.
Autism spectrum disorder common variants associated with regional lobe volume variations at birth: cross-sectional study in 273 European term neonates in developing human connectome project
Authors: Le Hai , Fenchel Daphna , Dimitrakopoulou Konstantina , Patel Hamel , Curtis Charles , Cordero-Grande Lucilio , Edwards A. David , Hajnal Joseph , Tournier Jacques-Donald , Deprez Maria , Cullen Harriet
Published: February 2025

Increasing lines of evidence suggest cerebral overgrowth in autism spectrum disorder (ASD) children in early life, but few studies have examined the effect of ASD common genetic variants on brain volumes in a general paediatric population. This study examined the association between ASD polygenic risk score (PRS) and volumes of the frontal, temporal, parietal, occipital, fronto-temporal and parieto-occipital lobes in 273 term-born infants of European ancestry in the developing Human Connectome Project. ASD PRS was positively associated with frontal (β = 0.027, p

FDR
 = 0.04) and fronto-temporal (β = 0.024, p

FDR
 = 0.01) volumes, but negatively with parietal (β = −0.037, p

FDR
 = 0.04) and parieto-occipital (β = −0.033, p

FDR
 = 0.01) volumes. This preliminary result suggests the potential involvement of ASD common genetic variants in early structural variations linked to ASD.
Metallothionein-3-mediated intracellular zinc mediates antioxidant and anti-inflammatory responses in the complete Freund’s adjuvant-induced inflammatory pain mouse model
Authors: Tran Ngoc Buu , Lee Sook-Jeong
Published: February 2025

Chronic inflammatory pain is often caused by peripheral tissue damage and persistent inflammation. This disease substantially affects patients’ physical and social well-being. We investigated the role of metallothionein-3 (MT3) in modulating complete Freund’s adjuvant (CFA)-induced intracellular Zn2+ activity in an MT3 knockout mouse model of inflammatory pain in the hind paw. The results demonstrated that increasing intracellular Zn2+ levels ameliorate deficits in motor behavior, as well as inflammation in the paw, spleen, and thymus. Furthermore, intracellular Zn2+ was crucial in regulating oxidative stress markers (glutathione, superoxide dismutase, catalase, and malondialdehyde) and inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, in MT3 knockout mice induced with CFA. This study highlights the critical role of MT3 in coordinating the intracellular interaction with Zn2+, which is vital for the immune systems’s protective functions. These interactions are fundamental for maintaining metal ion homeostasis and regulating the synthesis of various biomolecules in the body.
High-altitude hypoxia aggravated neurological deficits in mice induced by traumatic brain injury via BACH1 mediating astrocytic ferroptosis
Authors: Zou Peng , Li Tianjing , Cao Zixuan , Yang Erwan , Bao Mingdong , Zhang Haofuzi , Zhang Zhuoyuan , Liu Dan , Zhang Min , Gao Xiangyu , Ge Junmiao , Jiang Xiaofan , Tian Zhicheng , Luo Peng
Published: February 2025

Traumatic brain injury (TBI) is one of the leading causes of disability and mortality, which was classified as low-altitude TBI and high-altitude TBI. A large amount of literature shows that high-altitude TBI is associated with more severe neurological impairments and higher mortality rates compared to low-altitude TBI, due to the special environment of high-altitude hypoxia. However, the role of high-altitude hypoxia in the pathogenesis of TBI remains unclear. In order to deeply investigate this scientific issue, we constructed a high-altitude hypoxic TBI model at different altitudes and used animal behavioral assessments (Modified neurological severity score, rotarod test, elevated plus maze test) as well as histopathological analyses (brain gross specimens, brain water content, Evans blue content, hypoxia inducible factor-1α, Hematoxylin-Eosin staining and ROS detection) to reveal its underlying principles and characteristics. We found that with higher altitude, TBI-induced neurological deficits were more severe and the associated histopathological changes were more significant. Single-nuclear RNA sequencing was subsequently employed to further reveal differential gene expression profiles in high-altitude TBI. We found a significant increase in ferroptosis of astrocytes in cases of high-altitude TBI compared to those at low-altitude TBI. Analyzing transcription factors in depth, we found that Bach1 plays a crucial role in regulating key molecules that induce ferroptosis in astrocytes following high-altitude TBI. Down-regulation of Bach1 can effectively alleviate high-altitude TBI-induced neurological deficits and histopathological changes in mice. In conclusion, high-altitude hypoxia may significantly enhance the ferroptosis of astrocytes and aggravate TBI by up-regulating Bach1 expression. Our study provides a theoretical foundation for further understanding of the mechanism of high-altitude hypoxic TBI and targeted intervention therapy.
Rac1-dependent regulation of osteoclast and osteoblast differentiation by developmentally regulated GTP-binding 2
Authors: Kim Jung Ha , Seong Semun , Kim Kabsun , Kim Inyoung , Park Jeong Woo , Koh Jeong-Tae , Kim Nacksung
Published: February 2025

Multiple small GTPases play crucial roles in bone homeostasis by regulating the differentiation and function of bone cells, including osteoclasts and osteoblasts. Here, we investigated whether developmentally regulated GTP-binding protein 2 (Drg2), a subfamily of the GTPase superfamily, could affect bone mass by regulating osteoclast and osteoblast differentiation. Downregulation of Drg2 using siRNA in bone marrow-derived macrophages inhibited osteoclast differentiation and function and Rac1 activation in vitro. Comparatively, Drg2 downregulation in calvarial-derived osteoprogenitor cells enhanced osteoblast differentiation and function in vitro. Rac1 activation was also suppressed by Drg2 downregulation in osteoprogenitor cells. Both osteoclast and osteoblast differentiation regulated by Drg2 downregulation were restored by suppressing Rac1 activity. Drg2-deficient mice showed increased bone mass due to a dramatic reduction in osteoclast numbers without significantly affecting the number of osteoblasts. Furthermore, Drg2 downregulation strongly inhibited RANKL-induced bone loss in vivo. In summary, Drg2 contributes to bone homeostasis by regulating the differentiation and function of osteoclasts and osteoblasts through Rac1 activation. In particular, the effect of Drg2 on osteoclasts is strong enough to regulate bone mass in vivo; therefore, Drg2 has significant potential for use as a therapeutic target in bone loss-related diseases.
Quadrupolar excitons in MoSe2 bilayers
Authors: Jasiński Jakub , Hagel Joakim , Brem Samuel , Wietek Edith , Taniguchi Takashi , Watanabe Kenji , Chernikov Alexey , Bruyant Nicolas , Dyksik Mateusz , Surrente Alessandro , Baranowski Michał , Maude Duncan K. , Malic Ermin , Plochocka Paulina
Published: February 2025

The quest for platforms to generate and control exotic excitonic states has greatly benefited from the advent of transition metal dichalcogenide (TMD) monolayers and their heterostructures. Among the unconventional excitonic states, quadrupolar excitons—a superposition of two dipolar excitons with anti-aligned dipole moments—are of great interest for applications in quantum simulations and for the investigation of many-body physics. Here, we unambiguously demonstrate the emergence of quadrupolar excitons in natural MoSe2 homobilayers, whose energy shifts quadratically in electric field. In contrast to trilayer systems, MoSe2 homobilayers have many advantages, which include a larger coupling between dipolar excitons. Our experimental observations are complemented by many-particle theory calculations offering microscopic insights in the formation of quadrupolar excitons. Our results suggest TMD homobilayers as ideal platform for the engineering of excitonic states and their interaction with light and thus candidate for carrying out on-chip quantum simulations.
Pulsed vector atomic magnetometer using an alternating fast-rotating field
Authors: Wang Tao , Lee Wonjae , Limes Mark , Kornack Thomas , Foley Elizabeth , Romalis Michael
Published: February 2025

We introduce a vector atomic magnetometer that employs a fast-rotating magnetic field applied to a pulsed 87Rb scalar atomic magnetometer. This approach enables simultaneous measurements of the total magnetic field and its two polar angles relative to the rotation plane. Operating in gradiometer mode, the magnetometer achieves a total field gradient sensitivity of 35

$${{{\rm{fT}}}}/\sqrt{{{{\rm{Hz}}}}}$$

fT
/

Hz

(0.7 parts per billion) and angular resolutions of 6

$${{{\rm{nrad}}}}/\sqrt{{{{\rm{Hz}}}}}$$

nrad
/

Hz

at a 50 μT Earth field strength. The noise spectra remain flat down to 1 Hz and 0.1 Hz, respectively. Here we show that this method overcomes several metrological challenges commonly faced by vector magnetometers and gradiometers. We propose a unique peak-altering modulation technique to mitigate systematic effects, including a newly identified dynamic heading error. Additionally, we establish the fundamental sensitivity limits of the sensor, demonstrating that its vector sensitivity approaches scalar sensitivity while preserving the inherent accuracy and calibration benefits of scalar sensors. This high-dynamic-range, ultrahigh-resolution magnetometer offers exceptional versatility for diverse applications.
Polygenic height prediction for the Han Chinese in Taiwan
Authors: Chang Chih-Hao , Chou Che-Yu , Raben Timothy G. , Chen Shih-Ann , Jong Yuh-Jyh , Wu Jeng-Yih , Yang Shun-Fa , Chen Hsiang-Cheng , Chen Yen-Lin , Chen Ming , Ma Gwo-Chin , Huang Chih-Yang , Wang Tso-Fu , Lee Sing-Lian , Hung Chen-Fang , Pang See-Tong , Widen Erik , Chang Yao-Ming , Yeh Erh-Chan , Wei Chun-Yu , Chen Chien-Hsiun , Hsu Stephen D. H. , Kwok Pui-Yan
Published: February 2025

Human height prediction based on genetic factors alone shows positive correlation, but predictors developed for one population perform less well when applied to population of different ancestries. In this study, we evaluated the utility of incorporating non-genetic factors in height predictors for the Han Chinese population in Taiwan. We analyzed data from 78,719 Taiwan Biobank (TWB) participants and 40,641 Taiwan Precision Medicine Initiative (TPMI) participants using genome-wide association study and multivariable linear regression least absolute shrinkage and selection operator (LASSO) methods to incorporate genetic and non-genetic factors for height prediction. Our findings establish that combining birth year (as a surrogate for nutritional status), age at measurement (to account for age-associated effects on height), and genetic profile data improves the accuracy of height prediction. This method enhances the correlation between predicted and actual height and significantly reduces the discrepancies between predicted and actual height in both males and females.
The current state, opportunities and challenges for upscaling private investment in biodiversity in Europe
Authors: zu Ermgassen Sophus O.S.E. , Hawkins Isobel , Lundhede Thomas , Liu Qian , Thorsen Bo Jellesmark , Bull Joseph W.
Published: February 2025

European countries have committed to ambitious upscaling of privately funded nature conservation. We review the status and drivers of biodiversity finance in Europe. By implementing semistructured interviews with 25 biodiversity finance key informants and three focus groups across Europe, we explore opportunities and challenges for upscaling private investment in nature. Opportunities arise from macroeconomic and regulatory changes, along with various technological and financial innovations and growing professional experience. However, persistent barriers to upscaling include the ongoing lack of highly profitable investment opportunities and the multitude of risks facing investors, including political, ecological and reputational risks influencing supply and demand of investment opportunities. Public policy plays the foundational role in creating and hindering these mechanisms. Public policy can create nature markets and investment opportunities, meanwhile agricultural subsidies and poor coordination between public funding sources undermine the supply of return-seeking investment opportunities. Investors demand derisking investments from uncertainties; in part caused by political uncertainty. These markets require profound state intervention to enable upscaling whilst achieving positive ecological outcomes; private investment will probably not upscale without major public policy change and public investment.
SKI complex loss renders 9p21.3-deleted or MSI-H cancers dependent on PELO
Authors: Borck Patricia C. , Boyle Isabella , Jankovic Kristina , Bick Nolan , Foster Kyla , Lau Anthony C. , Parker-Burns Lucy I. , Lubicki Daniel A. , Li Tianxia , Borah Ashir A. , Lofaso Nicholas J. , Das Sharma Sohani , Chan Tessla , Kishen Riya V. , Adeagbo Anisah , Raghavan Srivatsan , Aquilanti Elisa , Prensner John R. , Krill-Burger J. Michael , Golub Todd R. , Campbell Catarina D. , Dempster Joshua M. , Chan Edmond M. , Vazquez Francisca
Published: February 2025

Cancer genome alterations often lead to vulnerabilities that can be used to selectively target cancer cells. Various inhibitors of such synthetic lethal targets have been approved by the FDA or are in clinical trials, highlighting the potential of this approach1–3. Here we analysed large-scale CRISPR knockout screening data from the Cancer Dependency Map and identified a new synthetic lethal target, PELO, for two independent molecular subtypes of cancer: biallelic deletion of chromosomal region 9p21.3 or microsatellite instability-high (MSI-H). In 9p21.3-deleted cancers, PELO dependency emerges from biallelic deletion of the 9p21.3 gene FOCAD, a stabilizer of the superkiller complex (SKIc). In MSI-H cancers, PELO is required owing to MSI-H-associated mutations in TTC37 (also known as SKIC3), a critical component of the SKIc. We show that both cancer subtypes converge to destabilize the SKIc, which extracts mRNA from stalled ribosomes. In SKIc-deficient cells, PELO depletion induces the unfolded protein response, a stress response to accumulation of misfolded or unfolded nascent polypeptides. Together, our findings indicate PELO as a promising therapeutic target for a large patient population with cancers characterized as MSI-H with deleterious TTC37 mutations or with biallelic 9p21.3 deletions involving FOCAD.
BioVars - A bioclimatic dataset for Europe based on a large regional climate ensemble for periods in 1971–2098
Authors: Reichmuth Anne , Rakovec Oldrich , Boeing Friedrich , Müller Sebastian , Samaniego Luis , Marx Andreas , Komischke Hanna , Schmidt Andreas , Doktor Daniel
Published: February 2025

Ongoing ecological research is concerned with analysing climate-induced changes in species distribution. For this purpose, the projection must have high-quality bioclimatic variables from historical and future climatic periods for the projection. To date, there are many global bioclimatic variables on this topic. Nevertheless, a consistent dataset with identical model variables from historic and projected periods is rare. We present 26 bioclimatic variables that are calculated based on a large ensemble consisting of 70 bias-adjusted GCM-RCM simulations for 1971–2098. Both, the historic and the projection periods were calculated using the same models to ensure consistency between the periods. The variables are validated against E-OBS observations from which we calculated the same bioclimatic variables. For projection periods we chose 20 year ranges between 2021–2098. Here, we offer two versions of them: (1) variables separated into RCP 2.6, 4.5 and 8.5, including percentiles among the realisations and within the RCPs; and (2) variables per realisation separately. We then extracted the temporal 5th, 50th and 95th percentile per period as representing values.
Differential resistance to nematode infection is associated with the genotype- and age-dependent pace of intestinal T cell homing
Authors: Adjah Joshua , Kapse Bhavya , Zhang Hongwei , Hartmann Susanne , Rausch Sebastian
Published: February 2025

The resistance of inbred mice to nematode infections varies depending on the extent of protective Th2 responses. Here, we compared two mouse lines differing in resistance to infection with the enteric nematode Heligmosomoides polygyrus bakeri despite the similar instruction of GATA-3+ T effector cells. Resistant BALB/c mice rapidly recruited high numbers of Th2 cells to the gut within the 1-week time frame required for larval development in the intestinal submucosa. C57BL/6 mice failed in the optimal control of early nematode fitness, with mucosal Th2 response peaking after 2 weeks when the larvae had left the tissue and relocated to the gut lumen as adult worms. The faster homing of Th2 cells to the gut of BALB/c mice is related to the extensive expression of the chemokine receptor CCR9 in GATA-3+ cells and higher frequencies of aldehyde dehydrogenase expressing dendritic cells present in mesenteric lymph nodes. Furthermore, nematode-infected older BALB/c mice displayed impaired resistance due to delayed mucosal homing of effector cells, which synergized with more numerous Th2/1 hybrid cells acting as IFN-γ-dependent confounders of type 2 responses. Hence, the distinct kinetics of effector cell recruitment to the infected gut and the quality of GATA-3+ T cell responses contribute to the genotype- and age-dependent resistance to intestinal nematode infections.
Bio-inspired 3D printing approach for bonding soft and rigid materials through underextrusion
Authors: Goshtasbi Arman , Grignaffini Luca , Sadeghi Ali
Published: February 2025

Vertebrate animals benefit from a combination of rigidity for structural support and softness for adaptation. Similarly, integrating rigidity and softness can enhance the versatility of soft robotics. However, the challenges associated with creating durable bonding interfaces between soft and rigid materials have limited the development of hybrid robots. Existing solutions require specialized machinery, such as polyjet 3D printers, which are not commonly available. In response to these challenges, we have developed a 3D printing technique that can be used with almost all commercially available FDM printers. This technique leverages the common issue of underextrusion to create a strong bond between soft and rigid materials. Underextrusion generates a porous structure, similar to fibrous connective tissues, that provides a robust interface with the rigid part through layer fusion, while the porosity enables interlocking with the soft material. Our experiments demonstrated that this method outperforms conventional adhesives commonly used in soft robotics, achieving nearly 200% of the bonding strength in both lap shear and peeling tests. Additionally, we investigated how different porosity levels affect bonding strength. We tested the technique under pressure scenarios critical to soft and hybrid robots and achieved three times more pressure than the current adhesion solution. Finally, we fabricated various hybrid robots using this technique to demonstrate the wide range of capabilities this approach and hybridity can bring to soft robotics.
Perceived urban environment elements associated with momentary and long-term well-being: An experience sampling method approach
Authors: Chen Yu-Ru , Nakagomi Atsushi , Hanazato Masamichi , Abe Noriyuki , Ide Kazushige , Kondo Katsunori
Published: February 2025

Well-being (WB) extends beyond physical health, as defined by the World Health Organization and encompasses two aspects: (1) long-term WB (LWB), such as overall life satisfaction; and (2) momentary WB (MWB), such as immediate mood. While research has demonstrated a positive association between one’s environment and LWB, limited studies have explored the association between environmental characteristics and MWB. We applied the experience sampling method (ESM) to collect data on location, perceived environmental characteristics, MWB, and LWB of adult participants living in Kashiwa-no-ha area, Kashiwa City, Japan. Structural equation modeling was used to calculate the correlation coefficients between different environments and both MWB and LWB. LWB was positively associated with MWB (standardized coefficient=0.24) and urban elements—cafés/restaurants/bars (0.11), cultural/sports/education facilities (0.04), and public spaces (0.11). Meanwhile, relaxing/clean (0.56) and natural environments (0.14) were associated with higher MWB. Conversely, vibrant environments (−0.14) and being on the move (−0.11) were linked to lower MWB. LWB was positively associated with being at cultural/sports/educational facilities (0.06), and vibrant (0.15) and communicative (0.13) urban settings. MWB was associated with various built environments, emphasizing the need for places like parks and cafés that promote a positive mood, and well-designed transportation and roads. These elements are important for developing urban areas that meet the physical requirements of residents while supporting their emotional and psychological well-being.
Deep visual proteomics reveals DNA replication stress as a hallmark of signet ring cell carcinoma
Authors: Kabatnik Sonja , Zheng Xiang , Pappas Georgios , Steigerwald Sophia , Padula Matthew P. , Mann Matthias
Published: February 2025

Signet Ring Cell Carcinoma (SRCC) is a rare and highly malignant form of adenocarcinoma with increasing incidence and poor prognosis due to late diagnosis and limited treatment options. We employed Deep Visual Proteomics (DVP), which combines AI-directed cell segmentation and classification with laser microdissection and ultra-high sensitivity mass spectrometry, for cell-type-specific proteomic analysis of SRCC across the bladder, prostate, seminal vesicle, and a lymph node of a single patient. DVP identified significant alterations in DNA damage response (DDR) proteins, particularly within the ATR and mismatch repair (MMR) pathways, indicating replication stress as a crucial factor in SRCC mutagenicity. Additionally, we observed substantial enrichment of immune-related proteins, reflecting high levels of cytotoxic T lymphocyte infiltration and elevated PD-1 expression. These findings suggest that pembrolizumab immunotherapy may be more effective than conventional chemotherapy for this patient. Our results provide novel insights into the proteomic landscape of SRCC, identify potential targets, and open up for personalized therapeutic strategies in managing SRCC.