bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unraveling the Molecular Reason of Opposing Effects of α‐Mangostin and Norfluoxetine on TREK‐2 at the Same Binding Site
Authors: Kim Gangrae , Van Nhung Thi Hong , Nam Joo Hyun , Lee Wook 
Published: August 2024

AbstractTWIK‐related K+ channel (TREK)‐2, expressed in sensory neurons, is involved in setting membrane potential, and its modulations contributes to the generation of nociceptive signals. Although acute and chronic pain is a common symptom experienced by patients with various conditions, most existing analgesics exhibit low efficacy and are associated with adverse effects. For this reason, finding the novel modulator of TREK‐2 is of significance for the development of new analgesics. Recent studies have shown that α‐Mangostin (α‐MG) activates TREK‐2, facilitating analgesic effects, yet the underlying molecular mechanisms remain elusive. Intriguingly, even though norfluoxetine (NFx) is known to inhibit TREK‐2, α‐MG is also observed to share a same binding site with NFx, and this implies that TREK‐2 might be modulated in a highly complicated manner. Therefore, we examine the mechanism of how TREK‐2 is activated by α‐MG using computational methods and patch clamp experiments in the present study. Based on these results, we offer an explanation of how α‐MG and NFx exhibit opposing effects at the same binding site of TREK‐2. These findings will broaden our understanding of TREK‐2 modulation, providing clues for designing novel analgesic drugs.
Biomechanical behavior of temporomandibular joint movements driven by mastication muscles
Authors: Cheng Kang‐jie , Zhang Qing‐qing , Zhang Feng , Wang Russell , Liu Yun‐feng 
Published: August 2024

AbstractSurgery of jawbones has a high potential risk of causing complications associated with temporomandibular joint disorder (TMD). The objective of this study was to investigate the effects of two drive modeling methods on the biomechanical behavior of the temporomandibular joint (TMJ) including articular disc during mandibular movements. A finite element (FE) model from a healthy human computed tomography was used to evaluate TMJ dynamic using two methods, namely, a conventional spatial‐oriented method (displacement‐driven) and a compliant muscle‐initiated method (masticatory muscle‐driven). The same virtual FE model was 3D printed and a custom designed experimental platform was established to validate the accuracy of experimental and theoretical results of the TMJ biomechanics during mandibular movements. The results show that stress distributed to TMJ and articular disc from mandibular movements provided better representation from the muscle‐driving approach than those of the displacement‐driven modeling. The simulation and experimental data exhibited significant strong correlations during opening, protrusion, and laterotrusion (with canonical correlation coefficients of 0.994, 0.993, and 0.932, respectively). The use of muscle‐driven modeling holds promise for more accurate forecasting of stress analysis of TMJ and articular disc during mandibular movements. The compliant approach to analyze TMJ dynamics would potentially contribute to clinic diagnosis and prediction of TMD resulting from occlusal disease and jawbone surgery such as orthognathic surgery or tumor resection.
Polymer‐Based Room‐Temperature Phosphorescence Materials Exhibiting Emission Lifetimes up to 4.6 s Under Ambient Conditions
Authors: Song Xiaoqing , Zhai Xiangxiang , Zeng Ying , Wang Guangming , Wang Tengyue , Li Yufang , Yan Qianqian , Chan Chin‐Yiu , Wang Biaobing , Zhang Kaka 
Published: August 2024

AbstractThe long‐emission‐lifetime nature of room‐temperature phosphorescence (RTP) materials lays the foundation of their applications in diverse areas. Despite the advantage of mechanical property, processability and solvent dispersity, the emission lifetimes of polymer‐based room‐temperature phosphorescence materials remain not particularly long because of the labile nature of organic triplet excited states under ambient conditions. Specifically, ambient phosphorescence lifetime (τP) longer than 2 s and even 4 s have rarely been reported in polymer systems. Here, luminescent compounds with small phosphorescence rate on the order of approximately 10−1 s−1 are designed, ethylene‐vinyl alcohol copolymer (EVOH) as polymer matrix and antioxidant 1010 to protect organic triplets are employed, and ultralong phosphorescence lifetime up to 4.6 s under ambient conditions by short‐term and low‐power excitation are achieved. The resultant materials exhibit high afterglow brightness, long afterglow duration, excellent processability into large area thin films, high transparency and thermal stability, which display promising anticounterfeiting and data encryption functions.
Environmental Influence on Stripe Formation at the Graphite‐Water Interface
Authors: Xu Chenglong , Qiao Greg G. , Nan Nan , Bao Lei 
Published: August 2024

AbstractUnderstanding the characteristics of graphite‐water interfaces is of scientific significance and practical importance. Ordered stripe structures have been observed at this interface, with their origins debated between condensed gas molecules and airborne hydrocarbons. Atomic force microscopy (AFM) studies have revealed variations in the morphology, formation and growth of these ordered structures. Here, we investigate the graphite‐water interface under different environmental conditions using PeakForce Quantitative Nanomechanical (PF‐QNM) AFM. Our findings reveal that stripe structures with 4 nm width and 0.5 nm periodicity, form and grow under wet laboratory conditions but not in pure inert gas or cleanroom environments. These stripes appear more readily when the graphite surface is immersed in water, with growth associated with gas nanodomains on the surface. This suggests that atmospheric contaminants migrate to the water‐graphite interface, potentially facilitated by gas states. These findings underscore the impact of environmental conditions on graphitic materials, providing new insights into the mechanisms underlying stripe formation and growth.
Carbon Suboxide, C3O2: A Hidden σ0π2 Carbene
Authors: Sultana Nargish , Sarmah Kangkan , Guha Ankur K. 
Published: August 2024

AbstractElectronic structure of carbon suboxide, C3O2, has been recently described as OC→C←CO having two lone pairs at the central carbon atom, thereby called as “Carbones”. Although it has a linear geometry, the presence of two lone pairs comes to fore when its reactivity is analyzed with two protons. However, no attention had been paid on its alternating reactivity with hydride ions. Herein, detailed quantum chemical calculations predict that carbon suboxide can also have significant hydride ion affinity. This reactivity is in tune with σ0π2 carbene character of carbon suboxide. This study also shows that such a σ0π2 carbene character is also prevalent in carbodiphosphorane, C(PH3)2. This bonding situation has been hitherto unexplored in “Carbone” chemistry.
Phosphoglycerate mutase 5 exacerbates alcoholic cardiomyopathy in male mice by inducing prohibitin‐2 dephosphorylation and impairing mitochondrial quality control
Authors: Tao Jun , Qiu Junxiong , Zheng Junmeng , Li Ruibing , Chang Xing , He Qingyong 
Published: August 2024

AbstractBackgroundThe induction of mitochondrial quality control (MQC) mechanisms is essential for the re‐establishment of mitochondrial homeostasis and cellular bioenergetics during periods of stress. Although MQC activation has cardioprotective effects in various cardiovascular diseases, its precise role and regulatory mechanisms in alcoholic cardiomyopathy (ACM) remain incompletely understood.MethodsWe explored whether two mitochondria‐related proteins, phosphoglycerate mutase 5 (Pgam5) and prohibitin 2 (Phb2), influence MQC in male mice during ACM.ResultsMyocardial Pgam5 expression was upregulated in a male mouse model of ACM. Notably, following ACM induction, heart dysfunction was markedly reversed in male cardiomyocyte‐specific Pgam5 knockout (Pgam5cKO) mice. Meanwhile, in alcohol‐treated male mouse‐derived neonatal cardiomyocytes, Pgam5 depletion preserved cell survival and restored mitochondrial dynamics, mitophagy, mitochondrial biogenesis and the mitochondrial unfolded protein response (mtUPR). We further found that in alcohol‐treated cardiomyocyte, Pgam5 binds Phb2 and induces its dephosphorylation at Ser91. Alternative transduction of phospho‐mimetic (Phb2S91D) and phospho‐defective (Phb2S9A) Phb2 mutants attenuated and enhanced, respectively, alcohol‐related mitochondrial dysfunction in cardiomyocytes. Moreover, transgenic male mice expressing Phb2S91D were resistant to alcohol‐induced heart dysfunction.ConclusionsWe conclude that ACM‐induced Pgam5 upregulation results in Pgam5‐dependent Phb2S91 dephosphorylation, leading to MQC destabilisation and mitochondrial dysfunction in heart. Therefore, modulating the Pgam5/Phb2 interaction could potentially offer a novel therapeutic strategy for ACM in male mice.Highlights
Pgam5 knockout attenuates alcohol‐induced cardiac histopathology and heart dysfunction in male mice.
Pgam5 KO reduces alcohol‐induced myocardial inflammation, lipid peroxidation and metabolic dysfunction in male mice.
Pgam5 depletion protects mitochondrial function in alcohol‐exposed male mouse cardiomyocytes.
Pgam5 depletion normalises MQC in ACM.
EtOH impairs MQC through inducing Phb2 dephosphorylation at Ser91.
Pgam5 interacts with Phb2 and induces Phb2 dephosphorylation.
Transgenic mice expressing a Ser91 phospho‐mimetic Phb2 mutant are resistant to ACM.
HL‐2A's ELM cycle simulations by integrating BOUT++'s drift MHD and transport code
Authors: Xu Xinliang , Wang Zhanhui , Li Nami , Wu Na , Zhou Yulin , Wu Xueke , Fu Cailong 
Published: August 2024

AbstractA new integrating model has been developed to couple tokamak edge multiscale magnetohydrodynamic (MHD) events and transport simulations, such as edge‐localized mode (ELM) cycles. As a proof of principle, we first start from a set of three‐field two‐fluid model equations, which includes the pressure, current, and vorticity. The equations are separated into the slowly evolving part of the axisymmetric component by taking a time average of the axisymmetric component. The time‐averaged fluxes, which are quadratic in fluctuating quantities, act as driven terms for the time‐averaged axisymmetric quantities that determine the plasma transport, and therefore the large‐scale evolution of the plasma profiles. Then the HL‐2A's ELM cycles are simulated using the model. Good agreements of ELM size and pedestal recovery time have been achieved for the solutions obtained from the coupled simulation compared with experiment. For one ELM cycle simulation, the coupled code can achieve a speedup of a factor of up to 30 over standalone code.
Shifts in fungal community diversity and potential function under natural forest succession and planted forest restoration in the Kunyu Mountains, East China
Authors: Zhu Ping , Hu Xinyu , Zou Qiang , Yang Xiaoyan , Jiang Bohan , Zuo Jincheng , Bai Xinfu , Song Jianqiang , Wu Nan , Hou Yuping 
Published: August 2024

AbstractSoil fungi participate in various ecosystem processes and are important factors driving the restoration of degraded forests. However, little is known about the changes in fungal diversity and potential functions under the development of different vegetation types during natural (secondary forest succession) and anthropogenic (reforestation) forest restoration. In this study, we selected typical forest succession sequences (including Pinus densiflora Siebold & Zucc., pine‐broadleaf mixed forest of P. densiflora and Quercus acutissima Carruth., and Q. acutissima), as well as natural secondary deciduous broadleaved mixed forests and planted forests of Robinia pseudoacacia on Kunyu Mountain for analysis. We used ITS rRNA gene sequencing to characterize fungal communities and used the FUNGuild database to predict fungal functional groups. The results showed that forest succession affected fungal β‐diversity, but not the α‐diversity. There was a significant increase in Basidiomycota and a decrease in Ascomycota in the later successional stage, accompanied by an increase in the functional groups of ectomycorrhizal fungi (ECM). Conversely, planted forests exhibited decreased fungal α‐diversity and altered community compositions, characterized by fewer Basidiomycota and more Ascomycota and Mucoromycota. Planted forests led to a decrease in the relative abundances of ECM and an increase in animal pathogens. The TK content was the major factor explaining the distinction in fungal communities among the three successional stages, whereas pH, AP, and NH4+ were the major factors explaining community variations between natural and planted forests. Changes in vegetation types significantly affected the diversity and functional groups of soil fungal communities during forest succession and reforestation, providing key insights for forest ecosystem management in temperate forests.
Direct and indirect effects of climate and seed dynamics on the breeding performance of a seed predator at the distribution edge
Authors: Oro Daniel , Freixas Lídia , Bartrina Carme , Míguez Silvia , Torre Ignasi 
Published: August 2024

AbstractMarginal populations usually have low densities and are considered to be particularly vulnerable to environmental stochasticity. Using data collected in nest boxes, we analyzed the breeding performance of the edible dormouse (Glis glis), an obligate hibernating rodent and a seed predator in deciduous forests, in two populations at the distribution range's edge. Despite being only 20 km apart from each other, Montseny is a large patch of mixed deciduous forests (oaks and beech), whereas Montnegre would be the harshest habitat, that is, a small, isolated patch with only oaks. First, we studied the differences in climate and tree cover change in the two populations. Second, we analyzed the direct and indirect roles of local climate conditions and seed availability on breeding performance over 10 years in each population. Finally, we explored the influence of tree cover change on the occupancy dynamics in the two populations. Our results showed contrasting responses between populations: in Montseny, asynchronous seed production between oaks and beech precluded skip breeding, and breeding performance increased with seed availability. Furthermore, dormice in Montseny may use pollen production to anticipate the amount of beech nut resources and adjust their breeding effort. Boxes showed higher occupancy and colonization and fewer extinctions in Montseny than in Montnegre, where seed availability did not drive breeding performance. Results from Montnegre suggest that skip breeding was an adaptive response to a more pulsed, harsher environment. Here, females produced a similar number of pups than at Montseny. Long‐term studies dealing with population responses in marginal habitats can lead to a deeper understanding of the capacities of organisms to adapt to harsh environments. Although local adaptation is frequently documented across various taxa, studies at the distribution edge may shed light on our still limited comprehension of the underlying mechanisms responsible for its occurrence.
Characterization and natural history of patients with LMNA‐related dilated cardiomyopathy in the phase 3 REALM‐DCM trial
Authors: Garcia‐Pavia Pablo , Lakdawala Neal K. , Sinagra Gianfranco , Ripoll‐Vera Tomas , Afshar Kia , Priori Silvia G. , Ware James S. , Owens Anjali , Li Huihua , Angeli Franca S. , Elliott Perry , MacRae Calum A. , Judge Daniel P. 
Published: August 2024

AbstractAimsLMNA‐related dilated cardiomyopathy (DCM) is a rare disease with an incompletely defined phenotype. The phase 3 REALM‐DCM trial evaluated a potential disease‐modifying therapy for LMNA‐related DCM but was terminated due to futility without safety concern. This study utilized pooled data from REALM‐DCM to descriptively characterize the phenotype and progression of LMNA‐related DCM in a contemporary cohort of patients using common heart failure (HF) measures.MethodsREALM‐DCM enrolled patients with stable LMNA‐related DCM, an implanted cardioverter defibrillator or cardiac resynchronization therapy defibrillator, and New York Heart Association (NYHA) Class II/III HF symptoms.ResultsBetween 2018 and 2022, 77 patients took part in REALM‐DCM. The median patient age was 53 years (range: 23–72), and 57% were male. Overall, 88% of patients had a pathogenic or likely pathogenic LMNA variant, and 12% had a variant of uncertain significance with a concordant phenotype. Among patients with confirmed sequencing, 55% had a missense variant. Atrial fibrillation was present in 60% of patients; 79% of all patients had NYHA Class II and 21% had NYHA Class III HF symptoms at baseline. Median (range) left ventricular ejection fraction (LVEF), 6 min walk test (6MWT) distance, Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ‐OS) score and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) concentration at baseline were 42% (23–62), 403 m (173–481), 67 (18–97) and 866 pg/mL (57–5248), respectively. LVEF, 6MWT distance and KCCQ‐OS score were numerically lower in patients who had NYHA Class III versus II symptoms at baseline (LVEF: 38% vs. 43%; 6MWT distance: 326 vs. 413 m; and KCCQ‐OS score: 43 vs. 70), whereas NT‐proBNP concentration was higher (1216 vs. 799 pg/mL). Median follow‐up was 73 weeks (range: 0.4–218; 73 in NYHA Class II and 75 in NYHA Class III). Patients displayed variable change from baseline in 6MWT, KCCQ‐OS and NT‐proBNP values during follow‐up. Overall, 25% of patients experienced ventricular tachycardia, and 8% had ventricular fibrillation. Ten (13%) patients met the composite endpoint of worsening HF (adjudicated HF‐related hospitalization or urgent care visit) or all‐cause death; six had NYHA Class II and four had NYHA Class III at baseline. All‐cause mortality occurred in 6 (8%) patients; three had NYHA Class II and three had NYHA Class III symptoms at baseline.ConclusionsFindings confirm the significant morbidity and mortality associated with LMNA‐related DCM despite the standard of care management. Typical measures of HF, including 6MWT distance, KCCQ‐OS score and NT‐proBNP concentration, were variable but correlated with NYHA class. An unmet treatment need remains among patients with LMNA‐related DCM. NCT03439514.
Mendelian randomization of plasma lipidome, inflammatory proteome and heart failure
Authors: Zheng Zequn , Tan Xuerui 
Published: August 2024

AbstractAimsHeart failure (HF) is a global health issue, with lipid metabolism and inflammation critically implicated in its progression. This study harnesses cutting‐edge, expanded genetic information for lipid and inflammatory protein profiles, employing Mendelian randomization (MR) to uncover genetic risk factors for HF.MethodsWe assessed genetic susceptibility to HF across 179 lipidomes and 91 inflammatory proteins using instrumental variables (IVs) from recent genome‐wide association studies (GWASs) and proteome‐wide quantitative trait loci (pQTL) studies. GWASs involving 47 309 HF cases and 930 014 controls were obtained from the Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES) Consortium. Data on 179 lipids from 7174 individuals in a Finnish cohort and 91 inflammatory proteins from a European pQTL study involving 14 824 individuals are available in the HGRI‐EBI catalogue. A two‐sample MR approach evaluated the associations, and a two‐step mediation analysis explored the mediation role of inflammatory proteins in the lipid–HF pathway. Sensitivity analyses, including MR‐RAPS (robust adjusted profile score) and MR‐Egger, ensured result robustness.ResultsGenetic IVs for 162 lipids and 74 inflammatory proteins were successfully identified. MR analysis revealed a genetic association between HF and 31 lipids. Among them, 18 lipids, including sterol ester (27:1/18:0), cholesterol, 9 phosphatidylcholines, phosphatidylinositol (16:0_20:4) and 6 triacylglycerols, were identified as HF risk factors [odds ratio (OR) = 1.037–1.368]. Cholesterol exhibited the most significant association with elevated HF risk [OR = 1.368, 95% confidence interval (CI) = 1.044–1.794, P = 0.023]. In the inflammatory proteome, leukaemia inhibitory factor receptor (OR = 0.841, 95% CI = 0.789–0.897, P = 1.08E‐07), fibroblast growth factor 19 (OR = 0.905, 95% CI = 0.830–0.988, P = 0.025) and urokinase‐type plasminogen activator (OR = 0.938, 95% CI = 0.886–0.994, P = 0.030) were causally negatively correlated with HF, whereas interleukin‐20 receptor subunit alpha (OR = 1.333, 95% CI = 1.094–1.625, P = 0.004) was causally positively correlated with HF. Mediation analysis revealed leukaemia inhibitory factor receptor (mediation proportion: 23.5%–25.2%) and urokinase‐type plasminogen activator (mediation proportion: 9.5%–10.7%) as intermediaries in the lipid–inflammation–HF pathway. No evidence of directional horizontal pleiotropy was observed (P > 0.05).ConclusionsThis study identifies a genetic connection between certain lipids, particularly cholesterol, and HF, highlighting inflammatory proteins that influence HF risk and mediate this relationship, suggesting new therapeutic targets and insights into genetic drivers in HF.
Hemophagocytic lymphohistiocytosis in an adult patient with super‐refractory status epilepticus
Authors: Haanpää Anna , Kämppi Leena , Kantonen Jonas , Myllykangas Liisa , Laakso Sini M. , Forss Nina 
Published: August 2024

AbstractThis case report presents a 38‐year‐old male patient who, after a febrile infection, developed super‐refractory status epilepticus and multiorgan failure, and died in 2 weeks despite the best possible intensive care. Autopsy revealed findings suggestive of hemophagocytic lymphohistiocytosis (HLH). This case shows that a rare immunological cause such as HLH may cause febrile infection‐related epilepsy syndrome (FIRES), and complications of intensive care can mask the physiological and laboratory changes in HLH.Plain Language SummaryThis case report presents a 38‐year‐old man who, after a febrile infection, developed intractable epileptic activity requiring intensive care treatment. During the intensive care, the patient showed signs of multiple organ damage and died in 2 weeks despite the best possible treatment. Autopsy revealed findings suggestive of hemophagocytic lymphohistiocytosis (HLH), which is a rare immune system regulation disorder leading to persistent inflammatory state and organ damages. This case shows that an immunological disorder like HLH may underlie treatment resistant fever‐related epileptic seizures.
Earth surface exchanges (ESEX) discussion of ‘Swelling and flow of expanding clays as a cause for nontectonic deformations in a glacial–interglacial environment: Holy Cross Mountains, Poland’ by E.Jurewicz, P.Karnkowski, A.Czarnecka‐Skwarek, E.Wójcik, I.Gawriuczenkow. Earth Surface Processes and Landforms2023: 1–16. https://doi.org/10.1002/esp.5609
Authors: Konon Andrzej , Domonik Andrzej , Ostrowski Szymon , Rybak‐Ostrowska Barbara , Wyglądała Michał 
Published: August 2024

AbstractIn a recently published report focused on the role of swelling of Triassic clays as the dominant process that led to the local steepening of competent Jurassic strata, its authors presented an opinion on the lack of evidence for the existence of the Gnieździska–Brzeziny strike‐slip fault along the contact between the Triassic and Jurassic rocks. This discussion presents the structural, geophysical, cartographic and geomechanical data indicating that the contact of Triassic and Jurassic rocks is defined by the vertical dextral strike‐slip Gnieździska–Brzeziny fault, which was formed after tilting of the beds in the Late Cretaceous. The presented evidence validates the tectonic deformation of Mesozoic rocks related to strike‐slip faulting. The dominant horizontal contraction across the fault planes within the restraining stepovers resulted in tilting of the beds, which is a well‐recognized phenomenon within the strike‐slip fault networks worldwide.