bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone deacetylase inhibition enhances extracellular vesicles from muscle to promote osteogenesis via miR-873-3p
Authors: Chen Ming , Li Yi , Zhang Mingming , Ge Siliang , Feng Taojin , Chen Ruijing , Shen Junmin , Li Ran , Wang Zhongqi , Xie Yong , Wang Duanyang , Liu Jiang , Lin Yuan , Chang Feifan , Chen Junyu , Sun Xinyu , Cheng Dongliang , Huang Xiang , Wu Fanfeng , Zhang Qinxiang , Cai Pingqiang , Yin Pengbin , Zhang Licheng , Tang Peifu 
Published: September 2024

AbstractRegular physical activity is widely recognized for reducing the risk of various disorders, with skeletal muscles playing a key role by releasing biomolecules that benefit multiple organs and tissues. However, many individuals, particularly the elderly and those with clinical conditions, are unable to engage in physical exercise, necessitating alternative strategies to stimulate muscle cells to secrete beneficial biomolecules. Histone acetylation and deacetylation significantly influence exercise-induced gene expression, suggesting that targeting histone deacetylases (HDACs) could mimic some exercise responses. In this study, we explored the effects of the HDAC inhibitor Trichostatin A (TSA) on human skeletal muscle myoblasts (HSMMs). Our findings showed that TSA-induced hyperacetylation enhanced myotube fusion and increased the secretion of extracellular vesicles (EVs) enriched with miR-873-3p. These TSA-EVs promoted osteogenic differentiation in human bone marrow mesenchymal stem cells (hBMSCs) by targeting H2 calponin (CNN2). In vivo, systemic administration of TSA-EVs to osteoporosis mice resulted in significant improvements in bone mass. Moreover, TSA-EVs mimicked the osteogenic benefits of exercise-induced EVs, suggesting that HDAC inhibition can replicate exercise-induced bone health benefits. These results demonstrate the potential of TSA-induced muscle-derived EVs as a therapeutic strategy to enhance bone formation and prevent osteoporosis, particularly for individuals unable to exercise. Given the FDA-approved status of various HDAC inhibitors, this approach holds significant promise for rapid clinical translation in osteoporosis treatment.
SOX4-BMI1 axis promotes non-small cell lung cancer progression and facilitates angiogenesis by suppressing ZNF24
Authors: Wen Ting , Zhang Xiao , Gao Yun , Tian Hong , Fan Lufeng , Yang Ping 
Published: September 2024

AbstractThe incidence of lung cancer has become the highest among all cancer types globally, also standing as a leading cause of cancer-related deaths. Lung cancer is broadly divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with the latter accounting for 85% of total cases. SRY-box transcription factor 4 (SOX4), a crucial transcription factor, has been found to play a key role in the development of various cancers. However, the association between SOX4 and NSCLC is still unclear. This study investigated the clinical relevance of SOX4 and its potential mechanisms in the progression of NSCLC. Analysis of our NSCLC patient cohort revealed a significant increase in SOX4 levels in cancerous tissues, indicating its role as an independent prognostic indicator for NSCLC. In vitro experiments demonstrated that elevated SOX4 expression facilitated NSCLC cell migration, invasion, and EMT. Functionally, SOX4 drives NSCLC progression by enhancing the transcription and expression of B-cell-specific moloney leukemia virus insertion site 1 (BMI1). The oncogenic impact of SOX4-induced BMI1 expression on NSCLC advancement was validated through both in vivo and in vitro studies. In addition, our findings showed that BMI1 promoted the ubiquitination of histone H2A (H2Aub), leading to decreased zinc finger protein 24 (ZNF24) expression, which subsequently triggered vascular endothelial growth factor A (VEGF-A) secretion in NSCLC cells, thereby promoting NSCLC angiogenesis. Moreover, we evaluated the therapeutic potential of a BMI1 inhibitor in combination with Bevacizumab for NSCLC treatment using orthotopic models. The data presented in our study reveal a previously unrecognized role of the SOX4-BMI1 axis in promoting NSCLC progression and angiogenesis. This research significantly contributes to our knowledge of the interplay between SOX4 and BMI1 in NSCLC, potentially paving the way for the development of targeted therapies for this disease.
Mast cell heparanase promotes breast cancer stem-like features via MUC1/estrogen receptor axis
Authors: Bongiorno Roberta , Lecchi Mara , Botti Laura , Bosco Oriana , Ratti Chiara , Fontanella Enrico , Mercurio Nicolò , Pratesi Pietro , Chiodoni Claudia , Verderio Paolo , Colombo Mario Paolo , Lecis Daniele 
Published: September 2024

AbstractBreast cancer is the most frequent type of tumor in women and is characterized by variable outcomes due to its heterogeneity and the presence of many cancer cell-autonomous and –non-autonomous factors. A major determinant of breast cancer aggressiveness is represented by immune infiltration, which can support tumor development. In our work, we studied the role of mast cells in breast cancer and identified a novel activity in promoting the tumor-initiating properties of cancer cells. Mast cells are known to affect breast cancer prognosis, but show different effects according to the diverse subtypes. Starting from the observation that co-injection of mast cells with limiting concentrations of cancer cells increased their in vivo engraftment rate, we characterized the molecular mechanisms by which mast cells promote the tumor stem-like features. We provide evidence that mast cell heparanase plays a pivotal role since both its activity and the stimulation of mast cells with heparan sulfate, the product of heparanase activity, are crucial for this process. Moreover, the pharmacological inhibition of heparanase prevents the function of mast cells. Our data show that soluble factors released by mast cells favor the expression of estrogen receptor in a MUC1-dependent manner. The MUC1/estrogen receptor axis is eventually essential for cancer stem-like features, specifically in HER2-negative cells, and promotes the capability of cancer cells to form mammospheres and express stem-related genes, also reducing their sensitivity to tamoxifen administration. Altogether our findings describe a novel mechanism by which mast cells could increase the aggressiveness of breast cancer uncovering a molecular mechanism displaying differences based on the specific breast cancer subtype.
Fatty acid synthase (FASN) is a tumor-cell-intrinsic metabolic checkpoint restricting T-cell immunity
Authors: Cuyàs Elisabet , Pedarra Stefano , Verdura Sara , Pardo Miguel Angel , Espin Garcia Roderic , Serrano-Hervás Eila , Llop-Hernández Àngela , Teixidor Eduard , Bosch-Barrera Joaquim , López-Bonet Eugeni , Martin-Castillo Begoña , Lupu Ruth , Pujana Miguel Angel , Sardanyès Josep , Alarcón Tomás , Menendez Javier A. 
Published: September 2024

AbstractFatty acid synthase (FASN)-catalyzed endogenous lipogenesis is a hallmark of cancer metabolism. However, whether FASN is an intrinsic mechanism of tumor cell defense against T cell immunity remains unexplored. To test this hypothesis, here we combined bioinformatic analysis of the FASN-related immune cell landscape, real-time assessment of cell-based immunotherapy efficacy in CRISPR/Cas9-based FASN gene knockout (FASN KO) cell models, and mathematical and mechanistic evaluation of FASN-driven immunoresistance. FASN expression negatively correlates with infiltrating immune cells associated with cancer suppression, cytolytic activity signatures, and HLA-I expression. Cancer cells engineered to carry a loss-of-function mutation in FASN exhibit an enhanced cytolytic response and an accelerated extinction kinetics upon interaction with cytokine-activated T cells. Depletion of FASN results in reduced carrying capacity, accompanied by the suppression of mitochondrial OXPHOS and strong downregulation of electron transport chain complexes. Targeted FASN depletion primes cancer cells for mitochondrial apoptosis as it synergizes with BCL-2/BCL-XL-targeting BH3 mimetics to render cancer cells more susceptible to T-cell-mediated killing. FASN depletion prevents adaptive induction of PD-L1 in response to interferon-gamma and reduces constitutive overexpression of PD-L1 by abolishing PD-L1 post-translational palmitoylation. FASN is a novel tumor cell-intrinsic metabolic checkpoint that restricts T cell immunity and may be exploited to improve the efficacy of T cell-based immunotherapy.
Native Hawaiian and Pacific Islander populations in genomic research
Authors: Ha Edra K. , Shriner Daniel , Callier Shawneequa L. , Riley Lorinda , Adeyemo Adebowale A. , Rotimi Charles N. , Bentley Amy R. 
Published: September 2024

AbstractThe role of genomic research and medicine in improving health continues to grow significantly, highlighting the need for increased equitable inclusion of diverse populations in genomics. Native Hawaiian and Pacific Islander (NHPI) communities are often missing from these efforts to ensure that the benefits of genomics are accessible to all individuals. In this article, we analyze the qualities of NHPI populations relevant to their inclusion in genomic research and investigate their current representation using data from the genome-wide association studies (GWAS) catalog. A discussion of the barriers NHPI experience regarding participating in research and recommendations to improve NHPI representation in genomic research are also included.
Collapse of metallicity and high-Tc superconductivity in the high-pressure phase of FeSe0.89S0.11
Authors: Reiss Pascal , McCollam Alix , Zajicek Zachary , Haghighirad Amir A. , Coldea Amalia I. 
Published: September 2024

AbstractWe investigate the high-pressure phase of the iron-based superconductor FeSe0.89S0.11 using transport and tunnel diode oscillator studies using diamond anvil cells. We construct detailed pressure-temperature phase diagrams that indicate that the superconducting critical temperature is strongly enhanced by more than a factor of four towards 40 K above 4 GPa. The resistivity data reveal signatures of a fan-like structure of non-Fermi liquid behaviour which could indicate the existence of a putative quantum critical point buried underneath the superconducting dome around 4.3 GPa. With further increasing the pressure, the zero-field electrical resistivity develops a non-metallic temperature dependence and the superconducting transition broadens significantly. Eventually, the system fails to reach a fully zero-resistance state, and the finite resistance at low temperatures becomes strongly current-dependent. Our results suggest that the high-pressure, high-Tc phase of iron chalcogenides is very fragile and sensitive to uniaxial effects of the pressure medium, cell design and sample thickness. This high-pressure region could be understood assuming a real-space phase separation caused by nearly concomitant electronic and structural instabilities.
Controllable orbital angular momentum monopoles in chiral topological semimetals
Authors: Yen Yun , Krieger Jonas A. , Yao Mengyu , Robredo Iñigo , Manna Kaustuv , Yang Qun , McFarlane Emily C. , Shekhar Chandra , Borrmann Horst , Stolz Samuel , Widmer Roland , Gröning Oliver , Strocov Vladimir N. , Parkin Stuart S. P. , Felser Claudia , Vergniory Maia G. , Schüler Michael , Schröter Niels B. M. 
Published: September 2024

AbstractThe emerging field of orbitronics aims to generate and control orbital angular momentum for information processing. Chiral crystals are promising orbitronic materials because they have been predicted to host monopole-like orbital textures, where the orbital angular momentum aligns isotropically with the electron’s crystal momentum. However, such monopoles have not yet been directly observed in chiral crystals. Here, we use circular dichroism in angle-resolved photoelectron spectroscopy to image orbital angular momentum monopoles in the chiral topological semimetals PtGa and PdGa. The spectra show a robust polar texture that rotates around the monopole as a function of photon energy. This is a direct consequence of the underlying magnetic orbital texture and can be understood from the interference of local atomic contributions. Moreover, we also demonstrate that the polarity of the monopoles can be controlled through the structural handedness of the host crystal by imaging orbital angular moment monopoles and antimonopoles in the two enantiomers of PdGa, respectively. Our results highlight the potential of chiral crystals for orbitronic device applications, and our methodology could enable the discovery of even more complicated nodal orbital angular momentum textures that could be exploited for orbitronics.
3D printed optimized electrodes for electrochemical flow reactors
Authors: Davis Jonathan T. , Jayathilake Buddhinie S. , Chandrasekaran Swetha , Wong Jonathan J. , Deotte Joshua R. , Baker Sarah E. , Beck Victor A. , Duoss Eric B. , Worsley Marcus A. , Lin Tiras Y. 
Published: September 2024

AbstractRecent advances in 3D printing have enabled the manufacture of porous electrodes which cannot be machined using traditional methods. With micron-scale precision, the pore structure of an electrode can now be designed for optimal energy efficiency, and a 3D printed electrode is not limited to a single uniform porosity. As these electrodes scale in size, however, the total number of possible pore designs can be intractable; choosing an appropriate pore distribution manually can be a complex task. To address this challenge, we adopt an inverse design approach. Using physics-based models, the electrode structure is optimized to minimize power losses in a flow reactor. The computer-generated structure is then printed and benchmarked against homogeneous porosity electrodes. We show how an optimized electrode decreases the power requirements by 16% compared to the best-case homogeneous porosity. Future work could apply this approach to flow batteries, electrolyzers, and fuel cells to accelerate their design and implementation.
Aggregation of the amyloid-β peptide (Aβ40) within condensates generated through liquid–liquid phase separation
Authors: Morris Owen M. , Toprakcioglu Zenon , Röntgen Alexander , Cali Mariana , Knowles Tuomas P. J. , Vendruscolo Michele 
Published: September 2024

AbstractThe deposition of the amyloid-β (Aβ) peptide into amyloid fibrils is a hallmark of Alzheimer’s disease. Recently, it has been reported that some proteins can aggregate and form amyloids through an intermediate pathway involving a liquid-like condensed phase. These observations prompted us to investigate the phase space of Aβ. We thus explored the ability of Aβ to undergo liquid–liquid phase separation, and the subsequent liquid-to-solid transition that takes place within the resulting condensates. Through the use of microfluidic approaches, we observed that the 40-residue form of Αβ (Αβ40) can undergo liquid–liquid phase separation, and that accessing a liquid-like intermediate state enables Αβ40 to self-assemble and aggregate into amyloid fibrils through this pathway. These results prompt further studies to investigate the possible role of Αβ liquid–liquid phase separation and its subsequent aggregation in the context of Alzheimer’s disease and more generally on neurodegenerative processes.
Investigating the potential of triclinic ABSe3 (A = Li, Na, K, Rb, Cs; B = Si, Ge, Sn) perovskites as a new class of lead-free photovoltaic materials
Authors: Mahmoud Eman Khalafalla , El-dek S. I. , Farghali Ahmed A. , Taha Mohamed 
Published: September 2024

AbstractIn recent years, chalcogenide perovskites have emerged as promising candidates with favorable structural, electrical, and optical properties for photovoltaic applications. This paper explores the structural, electronic, and optical characteristics of ABSe3 perovskites (where A = Li, Na, K, Rb, Cs; B = Si, Ge, Sn) in their triclinic crystallographic phases using density functional theory. The stability of these materials is ensured by calculating formation energies, tolerance factors (Tf), and phonon dispersion. The Eform values of all ABSe3 are negative, suggesting favorable thermodynamic stability. The Tf values range between 0.82 and 1.1, which is consistent with stable perovskites. The phonon dispersion analysis of the chalcogenide perovskites revealed no imaginary frequencies in any of the vibrational modes, confirming their stability. The electronic band structures and corresponding density of states are computed to unveil the semiconducting nature of the studied compounds. These perovskites are promising for high-performance solar cells due to their indirect bandgaps (Eg, 1.10–2.33 eV) and a small difference between these indirect and direct gaps (0.149–0.493 eV). The Eg values increase as the ionic radii of A-site elements increase (Li < Na < K < Rb < Cs). At the B-site, Si-based chalcogenides have the largest Eg values, followed by Sn-based and then Ge-based materials. Furthermore, optical properties such as the real part and imaginary part of the dielectric function, refractive index extinction coefficient, optical conductivity, absorption coefficient, reflectivity, and energy loss are predicted within the energy range of 0–50 eV. Several ABSe3 materials, particularly LiGeSe3 and NaGeSe3, demonstrated optical properties comparable to both traditional and emerging materials, suggesting their potential for effective use in solar cells.
NIR-ViS-UV broadband absorption in ultrathin electrochemically-grown, graded index nanoporous platinum films
Authors: Stanca Sarmiza-Elena , Rayapati Venkata R. , Chakraborty Abhik , Dellith Jan , Fritzsche Wolfgang , Zieger Gabriel , Schmidt Heidemarie 
Published: September 2024

AbstractNanoporous platinum broadband absorber has attracted interest in thermosensorics and IR photodetection due to its unique properties. In this work we report the physical mechanism underlying broadband absorption in electrochemically-grown, nanoporous Pt films by analyzing NIR-ViS-UV spectral ellipsometry data of nanoporous Pt films in dependence on the Pt film thickness (27, 35, 38, 48 nm). For the two thinner films a single layer model with a graded optical index Pt surface layer was used. For the two thicker films a two-layer optical model with a constant optical index Pt substrate layer and a graded optical index Pt surface layer was used. The graded optical index of the Pt surface layer reduces surface reflectivity and the constant optical index Pt substrate layer supports multiple reflections in the Pt film. Finally, we relate the thickness dependent optical index with the nanostructure of the nanoporous Pt film, which can be controlled in the electrochemical growth process. We observed that while in the transverse plane the multilayer exhibits graded refractive index, in the top horizontal planes the multilayer assembly exhibits discontinuous refractive index values due to the distribution of platinum crystal islands in air, which allows a metamaterial behavior of the whole system.
Talking about diseases; developing a model of patient and public-prioritised disease phenotypes
Authors: Slater Karin , Schofield Paul N. , Wright James , Clift Paul , Irani Anushka , Bradlow William , Aziz Furqan , Gkoutos Georgios V. 
Published: September 2024

AbstractDeep phenotyping describes the use of standardised terminologies to create comprehensive phenotypic descriptions of biomedical phenomena. These characterisations facilitate secondary analysis, evidence synthesis, and practitioner awareness, thereby guiding patient care. The vast majority of this knowledge is derived from sources that describe an academic understanding of disease, including academic literature and experimental databases. Previous work indicates a gulf between the priorities, perspectives, and perceptions held by different healthcare stakeholders. Using social media data, we develop a phenotype model that represents a public perspective on disease and compare this with a model derived from a combination of existing academic phenotype databases. We identified 52,198 positive disease-phenotype associations from social media across 311 diseases. We further identified 24,618 novel phenotype associations not shared by the biomedical and literature-derived phenotype model across 304 diseases, of which we considered 14,531 significant. Manifestations of disease affecting quality of life, and concerning endocrine, digestive, and reproductive diseases were over-represented in the social media phenotype model. An expert clinical review found that social media-derived associations were considered similarly well-established to those derived from literature, and were seen significantly more in patient clinical encounters. The phenotype model recovered from social media presents a significantly different perspective than existing resources derived from biomedical databases and literature, providing a large number of associations novel to the latter dataset. We propose that the integration and interrogation of these public perspectives on the disease can inform clinical awareness, improve secondary analysis, and bridge understanding and priorities across healthcare stakeholders.
Graft survival of major histocompatibility complex deficient stem cell-derived retinal cells
Authors: Ishida Masaaki , Masuda Tomohiro , Sakai Noriko , Nakai-Futatsugi Yoko , Kamao Hiroyuki , Shiina Takashi , Takahashi Masayo , Sugita Sunao 
Published: September 2024

Abstract
Background
Gene editing of immunomodulating molecules is a potential transplantation strategy to control immune rejection. As we noticed the successful transplantation of retinal pigment epithelium (RPE) derived from embryonic stem cells of a cynomolgus monkey that accidentally lacked MHC class II (MHC-II) molecules, we hypothesized immune rejection could be evaded by suppressing MHC-II.

Methods
Gene editing by the Crispr/Cas9 system was performed in induced pluripotent stem cells derived from a cynomolgus monkey (miPSCs) for targeted deletion of the gene coding class II MHC trans-activator (CIITA). Then the CIITA-knocked out miPSCs were differentiated into RPE cells to generate miPSC-derived MHC-II knockout RPE. The MHC-II knockout or wild-type RPEs were transplanted into the eyes of healthy cynomolgus monkeys. All monkeys used in this study were male.

Results
Here we show when MHC-II knockout RPE are transplanted into monkey eyes, they show suppressed immunogenicity with no infiltration of inflammatory cells, leading to successful engraftment.

Conclusions
Our results reasonably evidence the efficacy of MHC-II knockout iPSC-RPE transplants for clinical application.
Identification of the GABARAP binding determinant in PI4K2A
Authors: Chen Yan , Barylko Barbara , Eichorst John P. , Mueller Joachim D. , Albanesi Joseph P. 
Published: September 2024

Abstract
GABARAP is a member of the ATG8 family of ubiquitin-like autophagy related proteins. It was initially discovered as a facilitator of GABA-A receptor translocation to the plasma membrane and has since been shown to promote the intracellular transport of a variety of other proteins under non-autophagic conditions. We and others have shown that GABARAP interacts with the Type II phosphatidylinositol 4-kinase, PI4K2A, and that this interaction is important for autophagosome-lysosome fusion. Here, we identify a 7-amino acid segment within the PI4K2A catalytic domain that contains the GABARAP interaction motif (GIM). This segment resides in an exposed loop that is not conserved in the other mammalian Type II PI 4-kinase, PI4K2B, explaining the specificity of GABARAP binding to the PI4K2A isoform. Mutation of the PI4K2A GIM inhibits GABARAP binding and PI4K2A-mediated recruitment of cytosolic GABARAP to subcellular organelles. We further show that GABARAP binds to mono-phosphorylated phosphoinositides, PI3P, PI4P, and PI5P, raising the possibility that these lipids contribute to the binding energies that drive GABARAP–protein interactions on membranes.