bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elucidating the role of S100A10 in CD8+ T cell exhaustion and HCC immune escape via the cPLA2 and 5-LOX axis
Authors: Wang Ganggang , Shen Xiaowei , Jin Wenzhi , Song Chao , Dong Meiyuan , Zhou Zhijie , Wang Xiaoliang 
Published: August 2024

AbstractHepatocellular carcinoma (HCC) is a common malignant tumor with a complex immune evasion mechanism posing a challenge to treatment. The role of the S100A10 gene in various cancers has garnered significant attention. This study aims to elucidate the impact of S100A10 on CD8+ T cell exhaustion via the cPLA2 and 5-LOX axis, thereby elucidating its role in immune evasion in HCC. By analyzing the HCC-related data from the GEO and TCGA databases, we identified differentially expressed genes associated with lipid metabolism and developed a prognostic risk model. Subsequently, through RNA-seq and PPI analyses, we determined vital lipid metabolism genes and downstream factors S100A10, ACOT7, and SMS, which were significantly correlated with CD8+ T cell infiltration. Given the most significant expression differences, we selected S100A10 for further investigation. Both in vitro and in vivo experiments were conducted, including co-culture experiments of CD8+ T cells with MHCC97-L cells, Co-IP experiments, and validation in an HCC mouse model. S100A10 was significantly overexpressed in HCC tissues and potentially regulates CD8+ T cell exhaustion and lipid metabolism reprogramming through the cPLA2 and 5-LOX axis. Silencing S100A10 could inhibit CD8+ T cell exhaustion, further suppressing immune evasion in HCC. S100A10 may activate the cPLA2 and 5-LOX axis, initiating lipid metabolism reprogramming and upregulating LTB4 levels, thus promoting CD8+ T cell exhaustion in HCC tissues, facilitating immune evasion by HCC cells, ultimately impacting the growth and migration of HCC cells. This research highlights the critical role of S100A10 via the cPLA2 and 5-LOX axis in immune evasion in HCC, providing new theoretical foundations and potential targets for diagnosing and treating HCC.
ALYREF promotes the metastasis of nasopharyngeal carcinoma by increasing the stability of NOTCH1 mRNA
Authors: Jin Yanan , Yao Jijin , Fu Jianchang , Huang Qitao , Luo Yilin , You Yafei , Zhang Wangjian , Zhong Qian , Xia Tianliang , Xia Liangping 
Published: August 2024

AbstractApproximately 70% of treatment failures in nasopharyngeal carcinoma (NPC) patients are attributed to distant metastasis, yet the underlying mechanisms remain unclear. RNA 5-methylcytosine (m5C) is an emerging regulatory modification that controls gene expression and plays a critical role in tumor progression. However, there is little information on the potential roles of RNA m5C modification in NPC metastasis. In this study, we found that the m5C reader Aly/REF export factor (ALYREF) is significantly upregulated in NPC, whereby its high expression is associated with metastasis and poor prognosis. ALYREF overexpression was found to promote tumor metastasis of NPC cells in vitro and in vivo. Mechanistically, m5C-modified NOTCH1 mRNA was identified as a target of ALYREF. Moreover, ALYREF was found to upregulate NOTCH1 expression by enhancing its RNA stability in an m5C modification-dependent manner, thereby promoting the activation of the NOTCH signaling pathway and facilitating NPC metastasis. Overall, our data reveal the crucial role of ALYREF in NPC metastasis and provide a potential therapeutic target for NPC.
Pyroptosis leads to loss of centrosomal integrity in macrophages
Authors: Bai Siyi , Martin-Sanchez Fatima , Brough David , Lopez-Castejon Gloria 
Published: August 2024

AbstractNLRP3 forms a multiprotein inflammasome complex to initiate the inflammatory response when macrophages sense infection or tissue damage, which leads to caspase-1 activation, maturation and release of the inflammatory cytokines interleukin-1β (IL-1β) and IL-18 and Gasdermin-D (GSDMD) mediated pyroptosis. NLRP3 inflammasome activity must be controlled as unregulated and chronic inflammation underlies inflammatory and autoimmune diseases. Several findings uncovered that NLRP3 inflammasome activity is under the regulation of centrosome localized proteins such as NEK7 and HDAC6, however, whether the centrosome composition or structure is altered during the inflammasome activation is not known. Our data show that levels of the centrosomal scaffold protein pericentrin (PCNT) are reduced upon NLRP3 inflammasome activation via different activators in human and murine macrophages. PCNT loss occurs in the presence of membrane stabilizer punicalagin, suggesting this is not a consequence of membrane rupture. We found that PCNT loss is dependent on NLRP3 and active caspases as MCC950 and pan caspase inhibitor ZVAD prevent its degradation. Moreover, caspase-1 and GSDMD are both required for this NLRP3-mediated PCNT loss because absence of caspase-1 or GSDMD triggers an alternative regulation of PCNT via its cleavage by caspase-3 in response to nigericin stimulation. PCNT degradation occurs in response to nigericin, but also other NLRP3 activators including lysomotropic agent L-Leucyl-L-Leucine methyl ester (LLOMe) and hypotonicity but not AIM2 activation. Our work reveals that the NLRP3 inflammasome activation alters centrosome composition highlighting the need to further understand the role of this organelle during inflammatory responses.
Combination of eribulin and anlotinib exerts synergistic cytotoxicity in retroperitoneal liposarcoma by inducing endoplasmic reticulum stress
Authors: Li Shuquan , Zhang Hongtao , Yu Hao , Wu Yifan , Yan Liang , Guan Xiaoya , Dong Bin , Zhao Min , Tian Xiuyun , Hao Chunyi , Wu Jianhui 
Published: August 2024

AbstractPrimary retroperitoneal liposarcoma (RLPS) is a rare heterogeneous tumor occurring within retroperitoneal space, and its overall survival has not improved much in the past few decades. Based on a small-sample clinical practice at our center, patients with RLPS can greatly benefit from anlotinib and eribulin combination. In this study, we investigated the combinational effect of anlotinib and eribulin on RLPS. In vitro experiments revealed that a low dose of anlotinib significantly enhances the cytotoxic effects of eribulin, leading to a remarkable suppression of RLPS cell proliferation, viability, colony formation, migration, and cell-cycle progression compared to individual drug treatments. At the organoid level, the combination treatment causes the spheroids in Matrigel to disintegrate earlier than the single-drug group. In vivo, RLPS patient-derived xenograft (PDX) models demonstrated that the combination of these two drugs can obviously exert a safe and effective anti-tumor effect. Through transcriptome analysis, we uncovered and validated that the synergistic effect mainly is induced by the endoplasmic reticulum stress (ERS) pathway both in vitro and in vivo. Further analyses indicate that anlotinib plus eribulin treatment results in micro-vessel density and PD-L1 expression alterations, suggesting a potential impact on the tumor microenvironment. This study extensively explored the combination regimen at multiple levels and its underlying molecular mechanism in RLPS, thus providing a foundation for translational medicine research.
Proximity labelling of pro-interleukin-1α reveals evolutionary conserved nuclear interactions
Authors: Wellens Rose , Tapia Victor S. , Seoane Paula I. , Bennett Hayley , Adamson Antony , Coutts Graham , Rivers-Auty Jack , Lowe Martin , Green Jack P. , Lopez-Castejon Gloria , Brough David , Hoyle Christopher 
Published: August 2024

AbstractInterleukin-1α is a suggested dual-function cytokine that diverged from interleukin-1β in mammals potentially by acquiring additional biological roles that relate to highly conserved regions in the pro-domain of interleukin-1α, including a nuclear localisation sequence and histone acetyltransferase-binding domains. Why evolution modified pro-interleukin-1α’s subcellular location and protein interactome, and how this shaped interleukin-1α’s intracellular role, is unknown. Here we show that TurboID proximity labelling with pro-interleukin-1α suggests a nuclear role for pro-interleukin-1α that involves interaction with histone acetyltransferases, including EP300. We also identify and validate inactivating mutations in the pro-interleukin-1α nuclear localisation sequence of multiple mammalian species, including toothed whales, castorimorpha and marsupials. However, histone acetyltransferase-binding domains are conserved in those species that have lost pro-interleukin-1α nuclear localisation. Together, these data suggest that histone acetyltransferase binding and nuclear localisation occurred together, and that while some species lost the nuclear localisation sequence in their pro-interleukin-1α, histone acetyltransferase binding ability was maintained. The nuclear localisation sequence was lost from several distinct species at different evolutionary times, suggesting convergent evolution, and that the loss of the nuclear localisation sequence confers some important biological outcome.
Achiral hard bananas assemble double-twist skyrmions and blue phases
Authors: Subert Rodolfo , Campos-Villalobos Gerardo , Dijkstra Marjolein 
Published: August 2024

AbstractSkyrmions are topologically protected, vortex-like structures found in various condensed-matter systems including helical ferromagnets and liquid crystals, typically arising from chiral interactions. Using extensive particle-based simulations, we demonstrate that non-chiral hard banana-shaped particles, governed solely by excluded-volume interactions, spontaneously stabilize skyrmion structures through the bend-flexoelectric effect. Under thin confinement, we observe the formation of quasi-2D layers of isolated skyrmions or dense skyrmion lattices. These structures, comprising a racemic mixture of left- and right-handed skyrmions, show resilience against thermal fluctuations while remaining responsive to external fields, offering intriguing possibilities for manipulation. We also find that the size of these skyrmions can be adjusted by the dimensions and curvature of the banana-shaped particles. In the absence of geometric frustration due to confinement, a blue phase III may emerge, characterized by a 3D network of chiral skyrmion filaments of the nematic director field within an isotropic background. Our findings provide valuable insights into stabilizing skyrmion lattices and blue phases, showcasing non-Gaussian fluid-like dynamics in systems of achiral hard particles. Furthermore, they highlight the remarkable capacity of these complex fluids in designing advanced functional materials with diverse applications in photonics and memory devices.
ProDOL: a general method to determine the degree of labeling for staining optimization and molecular counting
Authors: Tashev Stanimir Asenov , Euchner Jonas , Yserentant Klaus , Hänselmann Siegfried , Hild Felix , Chmielewicz Wioleta , Hummert Johan , Schwörer Florian , Tsopoulidis Nikolaos , Germer Stefan , Saßmannshausen Zoe , Fackler Oliver T. , Klingmüller Ursula , Herten Dirk-Peter 
Published: August 2024

AbstractDetermining the label to target ratio, also known as the degree of labeling (DOL), is crucial for quantitative fluorescence microscopy and a high DOL with minimal unspecific labeling is beneficial for fluorescence microscopy in general. Yet robust, versatile and easy-to-use tools for measuring cell-specific labeling efficiencies are not available. Here we present a DOL determination technique named protein-tag DOL (ProDOL), which enables fast quantification and optimization of protein-tag labeling. With ProDOL various factors affecting labeling efficiency, including substrate type, incubation time and concentration, as well as sample fixation and cell type can be easily assessed. We applied ProDOL to investigate how human immunodeficiency virus-1 pathogenesis factor Nef modulates CD4 T cell activation measuring total and activated copy numbers of the adapter protein SLP-76 in signaling microclusters. ProDOL proved to be a versatile and robust tool for labeling calibration, enabling determination of labeling efficiencies, optimization of strategies and quantification of protein stoichiometry.
Synthesis, molecular modelling and evaluation of larvicidal efficacy of annulated Benzo[h]chromenes against Culex pipiens L. Larvae
Authors: El-Sayed Mahmoud K. F. , Elshahawi Manal M. , Abu El-Azm Fatma S. M. , Hosni Eslam M. , Kamal Mahmoud , Ali Yasmeen M. 
Published: August 2024

AbstractA new series of substituted benzo[h]chromene, benzochromenopyrimidine, and benzochromenotriazolopyrimidine derivatives were synthesized via chemical transformations of iminonitrile, ethoxymethylene amino, and cyanomethylene functionalities. The chemical structures of the synthesized compounds were assured by spectroscopic data and elemental analysis. The larvicidal efficacy of these compounds against Culex pipiens L. larvae was investigated, revealing potent insecticidal activity, particularly for compounds 6, 10, and 16, exceeding that of the standard insecticide chlorpyrifos. The mode of action of these compounds was explored through molecular docking studies, indicating their potential as acetylcholine esterase (AChE) inhibitors and nicotinic acetylcholine receptors (nAChR) blockers. The structure–activity relationship analysis highlighted the influence of substituents and fused heterocyclic rings on larvicidal potency. These findings suggest that the synthesized compounds hold promise as potential candidates for developing novel and effective mosquito control agents.
Bitter tastants relax the mouse gallbladder smooth muscle independent of signaling through tuft cells and bitter taste receptors
Authors: Keshavarz Maryam , Ruppert Anna-Lena , Meiners Mirjam , Poharkar Krupali , Liu Shuya , Mahmoud Wafaa , Winterberg Sarah , Hartmann Petra , Mermer Petra , Perniss Alexander , Offermanns Stefan , Kummer Wolfgang , Schütz Burkhard 
Published: August 2024

AbstractDisorders of gallbladder motility can lead to serious pathology. Bitter tastants acting upon bitter taste receptors (TAS2R family) have been proposed as a novel class of smooth muscle relaxants to combat excessive contraction in the airways and other organs. To explore whether this might also emerge as an option for gallbladder diseases, we here tested bitter tastants for relaxant properties and profiled Tas2r expression in the mouse gallbladder. In organ bath experiments, the bitter tastants denatonium, quinine, dextromethorphan, and noscapine, dose-dependently relaxed the pre-contracted gallbladder. Utilizing gene-deficient mouse strains, neither transient receptor potential family member 5 (TRPM5), nor the Tas2r143/Tas2r135/Tas2r126 gene cluster, nor tuft cells proved to be required for this relaxation, indicating direct action upon smooth muscle cells (SMC). Accordingly, denatonium, quinine and dextromethorphan increased intracellular calcium concentration preferentially in isolated gallbladder SMC and, again, this effect was independent of TRPM5. RT-PCR revealed transcripts of Tas2r108, Tas2r126, Tas2r135, Tas2r137, and Tas2r143, and analysis of gallbladders from mice lacking tuft cells revealed preferential expression of Tas2r108 and Tas2r137 in tuft cells. A TAS2R143-mCherry reporter mouse labeled tuft cells in the gallbladder epithelium. An in silico analysis of a scRNA sequencing data set revealed Tas2r expression in only few cells of different identity, and from in situ hybridization histochemistry, which did not label distinct cells. Our findings demonstrate profound tuft cell- and TRPM5-independent relaxing effects of bitter tastants on gallbladder smooth muscle, but do not support the concept that these effects are mediated by bitter receptors.
Impact of surface charge density modulation on ion transport in heterogeneous nanochannels
Authors: Alinezhad Amin , Khatibi Mahdi , Ashrafizadeh Seyed Nezameddin 
Published: August 2024

AbstractThe PNP nanotransistor, consisting of emitter, base, and collector regions, exhibits distinct behavior based on surface charge densities and various electrolyte concentrations. In this study, we investigated the impact of surface charge density on ion transport behavior within PNP nanotransistors at different electrolyte concentrations and applied voltages. We employed a finite-element method to obtain steady-state solutions for the Poisson–Nernst-Planck and Navier–Stokes equations. The ions form a depletion region, influencing the ionic current, and we analyze the influence of surface charge density on the depth of this depletion region. Our findings demonstrate that an increase in surface charge density results in a deeper depletion zone, leading to a reduction in ionic current. However, at very low electrolyte concentrations, an optimal surface charge density causes the ion current to reach its lowest value, subsequently increasing with further increments in surface charge density. As such, at $${V}_{app}=+1 \text{V}$$

V

app

=
+
1
V

and $${C}_{0}=1 \text{mM}$$

C
0

=
1
mM

, the ionic current increases by 25% when the surface charge density rises from 5 to 20 $$\text{mC}.{\text{m}}^{-2}$$

mC
.

m

-
2

, whereas at $${C}_{0}=10 \text{mM}$$

C
0

=
10
mM

, the ionic current decreases by 65% with the same increase in surface charge density. This study provides valuable insights into the behavior of PNP nanotransistors and their potential applications in nanoelectronic devices.
A dual-functional electrolyte additive displaying hydrogen bond fusion enables highly reversible aqueous zinc ion batteries
Authors: Zhang Qiuxia , Gao Xuan , Liu Kejiang , Gao Nan , Cheng Shaoheng , Dai Yuhang , Dong Haobo , Liu Junsong , He Guanjie , Li Hongdong 
Published: August 2024

AbstractIn recent years, aqueous zinc-ion batteries (AZIBs) have attracted significant attention in energy storage due to their notable advantages, including high safety, low cost, high capacity, and environmental friendliness. However, side reactions like hydrogen evolution and zinc (Zn) dendrites can significantly impact their Coulombic efficiency (CE) and lifespan. Effectively addressing these issues has become a focus of research in this field. In our study, dimethyl sulfoxide (DMSO) and nanodiamonds (NDs) were used to optimize the electrolyte of AZIBs. Benefiting from the hydrogen bond fusion of DMSO and NDs, which regulates the Zn deposition behavior, effectively inhibiting the growth of Zn dendrites, hydrogen evolution, and corrosion. The Zn | |Zn symmetric cells using NDs-DMSO-ZS demonstrate exceptional cycling stability for over 1500 h at 1 mA cm−2, while the Zn//Cu asymmetric cells achieve up to 99.8% CE at 2 mA cm−2. This study not only shows the application prospects of electrolyte optimization in enhancing AZIBs performance, but also provides a reference for the advancement of electrolyte technology in advanced AZIBs technology.
Towards robust dichroism in angle-resolved photoemission
Authors: Schusser J. , Orio H. , Ünzelmann M. , Heßdörfer J. , Masilamani M. P. T. , Diekmann F. , Rossnagel K. , Reinert F. 
Published: August 2024

AbstractDichroic techniques are highly relevant in the field of topological materials, layered systems, and spin-polarized electronic states. Dichroism in angle-resolved photoemission is per se a matrix element effect, which depends on the initial and final states as well as on the perturbation by the light field. Although matrix element effects in ARPES such as dichroism are important for addressing properties of the initial state wave functions, the results can strongly depend on experimental geometry or final state effects. Combining experimental data on bulk WSe2 taken at soft x-ray photon energies with state-of-the-art photoemission calculations, we demonstrate that a dichroic observable called time-reversal dichroism remains unaffected against variation of photon energy, light polarization, and the angle of incidence. We demonstrate a direct link of TRDAD obtained with both linearly and circularly polarized photons to the initial state properties indicating its broad applicability. The robustness of this matrix element effect indicates a considerable benefit over other dichroic techniques and encourages further experimental and theoretical investigations.
Transglutaminase 2-mediated histone monoaminylation and its role in cancer
Authors: Li Huapeng , Wu Jinghua , Zhang Nan , Zheng Qingfei 
Published: August 2024

Abstract
Transglutaminase 2 (TGM2) has been known as a well-characterized factor regulating the progression of multiple types of cancer, due to its multifunctional activities and the ubiquitous signaling pathways it is involved in. As a member of the transglutaminase family, TGM2 catalyzes protein post-translational modifications (PTMs), including monoaminylation, amide hydrolysis, cross-linking, etc., through the transamidation of variant glutamine-containing protein substrates. Recent discoveries revealed histone as an important category of TGM2 substrates, thus identifying histone monoaminylation as an emerging epigenetic mark, which is highly enriched in cancer cells and possesses significant regulatory functions of gene transcription. In this review, we will summarize recent advances in TGM2-mediated histone monoaminylation as well as its role in cancer and discuss the key research methodologies to better understand this unique epigenetic mark, thereby shedding light on the therapeutic potential of TGM2 as a druggable target in cancer treatment.
The Relationship Between Executive Functioning and Narrative Language Abilities in Aphasia
Authors: Dutta Manaswita , Murray Laura L. , Stark Brielle C. 
Published: August 2024

Purpose:
Although individuals with aphasia commonly exhibit challenges in executive functioning (EF) and spoken discourse, there is limited research exploring connections between these abilities within this specific population. Therefore, this study investigated the relationship between verbal and nonverbal EF and narrative productions in aphasia using a multilevel linguistic approach.

Method:
Participants included 22 persons with aphasia (PWA) and 24 age- and education-matched, neurologically healthy controls (NHC). All participants completed assessments for EF and a story retelling task. Narrative samples were analyzed for microlinguistic (productivity, lexical and syntactic features, semantic content, word and sentence errors) and macrolinguistic (coherence, informational content, organization, and language use) characteristics. Correlational analyses were employed to explore the relationships among narrative variables. EF factors, extracted from principal component analysis, were used as predictive variables in hierarchical stepwise regression analyses to evaluate their role in predicting narrative performances of PWA and NHC.

Results:
Relative to NHC, PWA exhibited impaired narrative performance affecting both microlinguistic and macrolinguistic levels. Breakdowns at the structural level (i.e., reduced productivity, syntax, lexical retrieval, and diversity) correlated with impaired story completeness, organization, and connectedness; this relationship was more prominent for PWA. Three EF factors representing (1) verbal EF, (2) verbal and nonverbal fluency, and (3) nonverbal EF were extracted. Factors 1 and 2 largely predicted narrative performance, whereas Factor 3 (i.e., nonverbal EF) contributed prominently to predicting macrolinguistic discourse performance in both groups although accounting for less variance in the data. Overall, lower EF scores, particularly verbal EF variables, predicted poor narrative performance in both groups.

Conclusions:
Our results indicate that both linguistic and extralinguistic cognitive abilities play a role in story retelling performances among PWA. Notably, both verbal and nonverbal EF skills were found to be correlated with narrative abilities. However, the extent of their contributions varied depending on the discourse levels assessed. These findings provide a significant contribution to our understanding of the cognitive factors associated with breakdowns in discourse among PWA and highlight the importance of comprehensive assessment of EF and discourse within this population.

Supplemental Material:

https://doi.org/10.23641/asha.26485627