bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose dysregulation in antipsychotic-naive first-episode psychosis: in silico exploration of gene expression signatures
Authors: Lee Jiwon , Xue Xiangning , Au Emily , McIntyre William B. , Asgariroozbehani Roshanak , Panganiban Kristoffer , Tseng George C. , Papoulias Maria , Smith Emily , Monteiro Jonathan , Shah Divia , Maksyutynska Kateryna , Cavalier Samantha , Radoncic Emril , Prasad Femin , Agarwal Sri Mahavir , Mccullumsmith Robert , Freyberg Zachary , Logan Ryan W. , Hahn Margaret K. 
Published: January 2024

AbstractAntipsychotic (AP)-naive first-episode psychosis (FEP) patients display early dysglycemia, including insulin resistance and prediabetes. Metabolic dysregulation may therefore be intrinsic to psychosis spectrum disorders (PSDs), independent of the metabolic effects of APs. However, the potential biological pathways that overlap between PSDs and dysglycemic states remain to be identified. Using meta-analytic approaches of transcriptomic datasets, we investigated whether AP-naive FEP patients share overlapping gene expression signatures with non-psychiatrically ill early dysglycemia individuals. We meta-analyzed peripheral transcriptomic datasets of AP-naive FEP patients and non-psychiatrically ill early dysglycemia subjects to identify common gene expression signatures. Common signatures underwent pathway enrichment analysis and were then used to identify potential new pharmacological compounds via Integrative Library of Integrated Network-Based Cellular Signatures (iLINCS). Our search results yielded 5 AP-naive FEP studies and 4 early dysglycemia studies which met inclusion criteria. We discovered that AP-naive FEP and non-psychiatrically ill subjects exhibiting early dysglycemia shared 221 common signatures, which were enriched for pathways related to endoplasmic reticulum stress and abnormal brain energetics. Nine FDA-approved drugs were identified as potential drug treatments, of which the antidiabetic metformin, the first-line treatment for type 2 diabetes, has evidence to attenuate metabolic dysfunction in PSDs. Taken together, our findings support shared gene expression changes and biological pathways associating PSDs with dysglycemic disorders. These data suggest that the pathobiology of PSDs overlaps and potentially contributes to dysglycemia. Finally, we find that metformin may be a potential treatment for early metabolic dysfunction intrinsic to PSDs.
Incidence of cardiovascular disease in healthy Swedish peripheral blood stem cell donors – a nationwide study
Authors: Pahnke Simon , Hägglund Hans , Larfors Gunnar 
Published: January 2024

AbstractGranulocyte colony-stimulating factor (G-CSF) is used in a majority of healthy donors to obtain peripheral blood stem cells for allogeneic stem cell transplantation. Since high levels of G-CSF activates endothelial cells and can induce a pro-coagulatory state, and fuelled by case reports of cardiovascular events in donors, some concerns have been raised about a potential for an increased risk of cardiovascular events for the donors after donation. We studied the incidence of cardiovascular disease following stem cell donation in a Swedish national register based cohort of 1098 peripheral blood stem cell donors between 1998 and 2016. The primary objective was to evaluate if the incidence of cardiovascular disease was increased for donors treated with G-CSF. The incidence of any new cardiovascular disease was 6.0 cases per 1000 person years, with a median follow up of 9.8 years. The incidence did not exceed that of age- sex- and residency-matched population controls (hazard ratio 0.90, 95% confidence interval (CI) 0.76–1.07,p-value 0.23), bone marrow donors, or non-donating siblings. Long-term cardiovascular disease incidence was not increased in this national register based study of peripheral blood stem cell donors treated with G-CSF.
Evaluation of apoptosis stimulating protein of TP53-1 (ASPP1/PPP1R13B) to predict therapy resistance and overall survival in acute myeloid leukemia (AML)
Authors: Schittenhelm Marcus M. , Kaiser Max , Győrffy Balázs , Kampa-Schittenhelm Kerstin M. 
Published: January 2024

AbstractASPP1 (PPP1R13B) belongs to a family of p53-binding proteins and enhances apoptosis by stimulation of p53-transactivation of selected proapoptotic target genes. It is preferentially expressed in hematopoietic stem cells (HSC) and together with p53 preserves the genomic integrity of the HSC pool. Consequently, dysfunction of ASPP1 has been associated with malignant transformation and development of acute lymphoblastic leukemias and lymphomas - whereas methylation of the promoter region is linked to reduced transcription and ultimately attenuated expression of ASPP1. The role of ASPP1 in AML is not known. We now show that impaired regulation of PPP1R13B contributes to the biology of leukemogenesis and primary therapy resistance in AML. PPP1R13B mRNA expression patterns thereby define a distinct prognostic profile - which is not reflected by the European leukemia net (ELN) risk score. These findings have direct therapeutic implications and we provide a strategy to restore ASPP1 protein levels using hypomethylating agents to sensitize cells towards proapoptotic drugs. Prospective clinical trials are warranted to investigate the role of ASPP1 (PPP1R13B) as a biomarker for risk stratification and as a potential therapeutic target to restore susceptibility to chemotherapy.
Death receptor 5 is required for intestinal stem cell activity during intestinal epithelial renewal at homoeostasis
Authors: Liu Jianbo , Liu Kaixuan , Wang Ying , Shi Ziru , Xu Runze , Zhang Yundi , Li Jingxin , Liu Chuanyong , Xue Bing 
Published: January 2024

AbstractIntestinal epithelial renewal, which depends on the proliferation and differentiation of intestinal stem cells (ISCs), is essential for epithelial homoeostasis. Understanding the mechanism controlling ISC activity is important. We found that death receptor 5 (DR5) gene deletion (DR5-/-) mice had impaired epithelial absorption and barrier function, resulting in delayed weight gain, which might be related to the general reduction of differentiated epithelial cells. In DR5-/- mice, the expression of ISC marker genes, the number of Olfm4+ ISCs, and the number of Ki67+ and BrdU+ cells in crypt were reduced. Furthermore, DR5 deletion inhibited the expression of lineage differentiation genes driving ISC differentiation into enterocytes, goblet cells, enteroendocrine cells, and Paneth cells. Therefore, DR5 gene loss may inhibit the intestinal epithelial renewal by dampening ISC activity. The ability of crypts from DR5-/- mice to form organoids decreased, and selective DR5 activation by Bioymifi promoted organoid growth and the expression of ISC and intestinal epithelial cell marker genes. Silencing of endogenous DR5 ligand TRAIL in organoids down-regulated the expression of ISC and intestinal epithelial cell marker genes. So, DR5 expressed in intestinal crypts was involved in the regulation of ISC activity. DR5 deletion in vivo or activation in organoids inhibited or enhanced the activity of Wnt, Notch, and BMP signalling through regulating the production of Paneth cell-derived ISC niche factors. DR5 gene deletion caused apoptosis and DNA damage in transit amplifying cells by inhibiting ERK1/2 activity in intestinal crypts. Inhibition of ERK1/2 with PD0325901 dampened the ISC activity and epithelial regeneration. In organoids, when Bioymifi’s effect in activating ERK1/2 activity was completely blocked by PD0325901, its role in stimulating ISC activity and promoting epithelial regeneration was also eliminated. In summary, DR5 in intestinal crypts is essential for ISC activity during epithelial renewal under homoeostasis.
Strain-induced specific orbital control in a Heusler alloy-based interfacial multiferroics
Authors: Okabayashi Jun , Usami Takamasa , Mahfudh Yatmeidhy Amran , Murakami Yuichi , Shiratsuchi Yu , Nakatani Ryoichi , Gohda Yoshihiro , Hamaya Kohei 
Published: January 2024

Abstract
For the development of spintronic devices, the control of magnetization by a low electric field is necessary. The microscopic origin of manipulating spins relies on the control of orbital magnetic moments (m
orb) by strain; this is essential for the high performance magnetoelectric (ME) effect. Herein, electric-field induced X-ray magnetic circular dichroism (XMCD) is used to determine the changes in m
orb by piezoelectric strain and clarify the relationship between the strain and m
orb in an interfacial multiferroics system with a significant ME effect; the system consists of the Heusler alloy Co2FeSi on a ferroelectric Pb(Mg1/3Nb2/3)O3-PbTiO3 substrate. Element-specific investigations of the orbital states by operando XMCD and the local environment via extended X-ray absorption fine structure (EXAFS) analysis show that the modulation of only the Fe sites in Co2FeSi primarily contributes to the giant ME effect. The density functional theory calculations corroborate this finding, and the growth of the high index (422) plane in Co2FeSi results in a giant ME effect. These findings elucidate the element-specific orbital control using reversible strain, called the ‘orbital elastic effect,’ and can provide guidelines for material designs with a giant ME effect.
Cobalt-free composite-structured cathodes with lithium-stoichiometry control for sustainable lithium-ion batteries
Authors: Chen Ke , Barai Pallab , Kahvecioglu Ozgenur , Wu Lijun , Pupek Krzysztof Z. , Ge Mingyuan , Ma Lu , Ehrlich Steven N. , Zhong Hui , Zhu Yimei , Srinivasan Venkat , Bai Jianming , Wang Feng 
Published: January 2024

AbstractLithium-ion batteries play a crucial role in decarbonizing transportation and power grids, but their reliance on high-cost, earth-scarce cobalt in the commonly employed high-energy layered Li(NiMnCo)O2 cathodes raises supply-chain and sustainability concerns. Despite numerous attempts to address this challenge, eliminating Co from Li(NiMnCo)O2 remains elusive, as doing so detrimentally affects its layering and cycling stability. Here, we report on the rational stoichiometry control in synthesizing Li-deficient composite-structured LiNi0.95Mn0.05O2, comprising intergrown layered and rocksalt phases, which outperforms traditional layered counterparts. Through multiscale-correlated experimental characterization and computational modeling on the calcination process, we unveil the role of Li-deficiency in suppressing the rocksalt-to-layered phase transformation and crystal growth, leading to small-sized composites with the desired low anisotropic lattice expansion/contraction during charging and discharging. As a consequence, Li-deficient LiNi0.95Mn0.05O2 delivers 90% first-cycle Coulombic efficiency, 90% capacity retention, and close-to-zero voltage fade for 100 deep cycles, showing its potential as a Co-free cathode for sustainable Li-ion batteries.
Cryo-EM structure and B-factor refinement with ensemble representation
Authors: Beton Joseph G. , Mulvaney Thomas , Cragnolini Tristan , Topf Maya 
Published: January 2024

AbstractCryo-EM experiments produce images of macromolecular assemblies that are combined to produce three-dimensional density maps. Typically, atomic models of the constituent molecules are fitted into these maps, followed by a density-guided refinement. We introduce TEMPy-ReFF, a method for atomic structure refinement in cryo-EM density maps. Our method represents atomic positions as components of a Gaussian mixture model, utilising their variances as B-factors, which are used to derive an ensemble description. Extensively tested on a substantial dataset of 229 cryo-EM maps from EMDB ranging in resolution from 2.1-4.9 Å with corresponding PDB and CERES atomic models, our results demonstrate that TEMPy-ReFF ensembles provide a superior representation of cryo-EM maps. On a single-model basis, it performs similarly to the CERES re-refinement protocol, although there are cases where it provides a better fit to the map. Furthermore, our method enables the creation of composite maps free of boundary artefacts. TEMPy-ReFF is useful for better interpretation of flexible structures, such as those involving RNA, DNA or ligands.
Cross-feeding promotes heterogeneity within yeast cell populations
Authors: Hu Kevin K. Y. , Suri Ankita , Dumsday Geoff , Haritos Victoria S. 
Published: January 2024

AbstractCellular heterogeneity in cell populations of isogenic origin is driven by intrinsic factors such as stochastic gene expression, as well as external factors like nutrient availability and interactions with neighbouring cells. Heterogeneity promotes population fitness and thus has important implications in antimicrobial and anticancer treatments, where stress tolerance plays a significant role. Here, we study plasmid retention dynamics within a population of plasmid-complemented ura3∆0 yeast cells, and show that the exchange of complementary metabolites between plasmid-carrying prototrophs and plasmid-free auxotrophs allows the latter to survive and proliferate in selective environments. This process also affects plasmid copy number in plasmid-carrying prototrophs, further promoting cellular functional heterogeneity. Finally, we show that targeted genetic engineering can be used to suppress cross-feeding and reduce the frequency of plasmid-free auxotrophs, or to exploit it for intentional population diversification and division of labour in co-culture systems.
A replacement strategy for regulating local environment of single-atom Co-SxN4−x catalysts to facilitate CO2 electroreduction
Authors: Pei Jiajing , Shang Huishan , Mao Junjie , Chen Zhe , Sui Rui , Zhang Xuejiang , Zhou Danni , Wang Yu , Zhang Fang , Zhu Wei , Wang Tao , Chen Wenxing , Zhuang Zhongbin 
Published: January 2024

AbstractThe performances of single-atom catalysts are governed by their local coordination environments. Here, a thermal replacement strategy is developed for the synthesis of single-atom catalysts with precisely controlled and adjustable local coordination environments. A series of Co-SxN4−x (x = 0, 1, 2, 3) single-atom catalysts are successfully synthesized by thermally replacing coordinated N with S at elevated temperature, and a volcano relationship between coordinations and catalytic performances toward electrochemical CO2 reduction is observed. The Co-S1N3 catalyst has the balanced COOH*and CO* bindings, and thus locates at the apex of the volcano with the highest performance toward electrochemical CO2 reduction to CO, with the maximum CO Faradaic efficiency of 98 ± 1.8% and high turnover frequency of 4564 h−1 at an overpotential of 410 mV tested in H-cell with CO2-saturated 0.5 M KHCO3, surpassing most of the reported single-atom catalysts. This work provides a rational approach to control the local coordination environment of the single-atom catalysts, which is important for further fine-tuning the catalytic performance.
C−F bond activation enables synthesis of aryl difluoromethyl bicyclopentanes as benzophenone-type bioisosteres
Authors: Chen Mingshuo , Cui Yuang , Chen Xiaoping , Shang Rui , Zhang Xiaheng 
Published: January 2024

AbstractBioisosteric design has become an essential approach in the development of drug molecules. Recent advancements in synthetic methodologies have enabled the rapid adoption of this strategy into drug discovery programs. Consequently, conceptionally innovative practices would be appreciated by the medicinal chemistry community. Here we report an expeditous synthetic method for synthesizing aryl difluoromethyl bicyclopentane (ADB) as a bioisostere of the benzophenone core. This approach involves the merger of light-driven C−F bond activation and strain-release chemistry under the catalysis of a newly designed N-anionic-based organic photocatalyst. This defluorinative coupling methodology enables the direct conversion of a wide variety of commercially available trifluoromethylaromatic C−F bonds (more than 70 examples) into the corresponding difluoromethyl bicyclo[1.1.1]pentanes (BCP) arenes/difluoromethyl BCP boronates in a single step. The strategy can also be applied to [3.1.1]and [4.1.1]propellane systems, providing access to analogues with different geometries. Moreover, we have successfully used this protocol to rapidly prepare ADB-substituted analogues of the bioactive molecule Adiporon. Biological testing has shown that the ADB scaffold has the potential to enhance the pharmacological properties of benzophenone-type drug candidates.
Machine-learning-accelerated design of high-performance platinum intermetallic nanoparticle fuel cell catalysts
Authors: Yin Peng , Niu Xiangfu , Li Shuo-Bin , Chen Kai , Zhang Xi , Zuo Ming , Zhang Liang , Liang Hai-Wei 
Published: January 2024

AbstractCarbon supported PtCo intermetallic alloys are known to be one of the most promising candidates as low-platinum oxygen reduction reaction electrocatalysts for proton-exchange-membrane fuel cells. Nevertheless, the intrinsic trade-off between particle size and ordering degree of PtCo makes it challenging to simultaneously achieve a high specific activity and a large active surface area. Here, by machine-learning-accelerated screenings from the immense configuration space, we are able to statistically quantify the impact of chemical ordering on thermodynamic stability. We find that introducing of Cu/Ni into PtCo can provide additional stabilization energy by inducing Co-Cu/Ni disorder, thus facilitating the ordering process and achieveing an improved tradeoff between specific activity and active surface area. Guided by the theoretical prediction, the small sized and highly ordered ternary Pt2CoCu and Pt2CoNi catalysts are experimentally prepared, showing a large electrochemically active surface area of ~90 m2 gPt‒1 and a high specific activity of ~3.5 mA cm‒2.
Functionally antagonistic polyelectrolyte for electro-ionic soft actuator
Authors: Nguyen Van Hiep , Oh Saewoong , Mahato Manmatha , Tabassian Rassoul , Yoo Hyunjoon , Lee Seong-Gyu , Garai Mousumi , Kim Kwang Jin , Oh Il-Kwon 
Published: January 2024

AbstractElectro-active ionic soft actuators have been intensively investigated as an artificial muscle for soft robotics due to their large bending deformations at low voltages, small electric power consumption, superior energy density, high safety and biomimetic self-sensing actuation. However, their slow responses, poor durability and low bandwidth, mainly resulting from improper distribution of ionic conducting phase in polyelectrolyte membranes, hinder practical applications to real fields. We report a procedure to synthesize efficient polyelectrolyte membranes that have continuous conducting network suitable for electro-ionic artificial muscles. This functionally antagonistic solvent procedure makes amphiphilic Nafion molecules to assemble into micelles with ionic surfaces enclosing non-conducting cores. Especially, the ionic surfaces of these micelles combine together during casting process and form a continuous ionic conducting phase needed for high ionic conductivity, which boosts the performance of electro-ionic soft actuators by 10-time faster response and 36-time higher bending displacement. Furthermore, the developed muscle shows exceptional durability over 40 days under continuous actuation and broad bandwidth below 10 Hz, and is successfully applied to demonstrate an inchworm-mimetic soft robot and a kinetic tensegrity system.
Oxophilic Ce single atoms-triggered active sites reverse for superior alkaline hydrogen evolution
Authors: Shen Fengyi , Zhang Zhihao , Wang Zhe , Ren Hao , Liang Xinhu , Cai Zengjian , Yang Shitu , Sun Guodong , Cao Yanan , Yang Xiaoxin , Hu Mingzhen , Hao Zhengping , Zhou Kebin 
Published: January 2024

AbstractThe state-of-the-art alkaline hydrogen evolution catalyst of united ruthenium single atoms and small ruthenium nanoparticles has sparked considerable research interest. However, it remains a serious problem that hydrogen evolution primarily proceeds on the less active ruthenium single atoms instead of the more efficient small ruthenium nanoparticles in the catalyst, hence largely falling short of its full activity potential. Here, we report that by combining highly oxophilic cerium single atoms and fully-exposed ruthenium nanoclusters on a nitrogen functionalized carbon support, the alkaline hydrogen evolution centers are facilely reversed to the more active ruthenium nanoclusters driven by the strong oxophilicity of cerium, which significantly improves the hydrogen evolution activity of the catalyst with its mass activity up to −10.1 A mg−1 at −0.05 V. This finding is expected to shed new light on developing more efficient alkaline hydrogen evolution catalyst by rational regulation of the active centers for hydrogen evolution.
Candidate biomarkers of EV-microRNA in detecting REM sleep behavior disorder and Parkinson’s disease
Authors: Li Yuanyuan , Cao Ying , Liu Wei , Chen Fangzheng , Zhang Hongdao , Zhou Haisheng , Zhao Aonan , Luo Ningdi , Liu Jun , Wu Ligang 
Published: January 2024

AbstractParkinson’s disease (PD) lacks reliable, non-invasive biomarker tests for early intervention and management. Thus, a minimally invasive test for the early detection and monitoring of PD and REM sleep behavior disorder (iRBD) is a highly unmet need for developing drugs and planning patient care. Extracellular vehicles (EVs) are found in a wide variety of biofluids, including plasma. EV-mediated functional transfer of microRNAs (miRNAs) may be viable candidates as biomarkers for PD and iRBD. Next-generation sequencing (NGS) of EV-derived small RNAs was performed in 60 normal controls, 56 iRBD patients and 53 PD patients to profile small non-coding RNAs (sncRNAs). Moreover, prospective follow-up was performed for these 56 iRBD patients for an average of 3.3 years. Full-scale miRNA profiles of plasma EVs were evaluated by machine-learning methods. After optimizing the library construction method for low RNA inputs (named EVsmall-seq), we built a machine learning algorithm that identified diagnostic miRNA signatures for distinguishing iRBD patients (AUC 0.969) and PD patients (AUC 0.916) from healthy individuals; and PD patients (AUC 0.929) from iRBD patients. We illustrated all the possible expression patterns across healthy-iRBD-PD hierarchy. We also showed 20 examples of miRNAs with consistently increasing or decreasing expression levels from controls to iRBD to PD. In addition, four miRNAs were found to be correlated with iRBD conversion. Distinct characteristics of the miRNA profiles among normal, iRBD and PD samples were discovered, which provides a panel of promising biomarkers for the identification of PD patients and those in the prodromal stage iRBD.