bluuebunny/crossref_metadata_2025 huggingface dataset:
Sedimentological Evidence for Pre‐Early Permian Continental Subduction in the Dabie Orogen, Central‐East China
Authors: Deng Tao , Hu Xiumian , Chew David , Wang Qin , Yu Jinhai , Drakou Foteini
Published: January 2024

How to constrain the onset of continental subduction and prograde metamorphism in an orogen remains a fundamental question. The widespread Triassic ultrahigh‐pressure (UHP) metamorphic rocks in the Dabie orogen in central‐east China are generally attributed to continental subduction. The earliest Triassic peripheral basins (the Huangshi, Yueshan and Nanjing basins) around the Dabie orogen represent an ideal archive to reconstruct the early evolution of the orogen. Here we present a multidisciplinary provenance study on these Triassic strata, including framework petrography and heavy mineral analyses combined with U‐Pb age and trace‐element analyses of detrital zircon, rutile and apatite. The abundant metapelitic lithics and muscovite grains, a heavy mineral population dominated by metamorphic apatite, and a significant Permian (270–290 Ma) age peak from U‐Pb age spectra of detrital zircon, rutile and apatite imply an Early Permian medium‐high grade metamorphic source in the uppermost structural levels of the Dabie orogen. Our provenance data indicate that the onset of northward continental subduction of the South China Block commenced no later than the Early Permian (c. 290 Ma). This event is clearly earlier and distinct from the more widespread Triassic UHP metamorphism of the Dabie orogen, suggesting that continental subduction and mountain‐basin interaction were protracted processes (>55 Myr, c. 290–235 Ma). When combined with other geological evidence, our results show that the prolonged continental subduction is not always preceded by subduction of oceanic crust.
Brine Drying and Salt Precipitation in Porous Media: A Microfluidics Study
Authors: Zhang Hui , Sun Zhonghao , Zhang Nan , Zhao Budi
Published: January 2024

Drying and salt precipitation in porous media impact various engineering disciplines, including carbon geological storage in brine reservoirs, with considerable hydraulic and mechanical effects. However, understanding the underlying mechanisms and controlling factors is limited due to the lack of pore‐scale observation and quantitative analysis. We design radial flow microfluidic chips with varying pore heterogeneity and wettability and quantify the pore‐scale dynamics of brine drying and salt precipitation using time‐lapse images and image processing techniques. The gas injection process determines the distribution of residual (drying) brine and is influenced by pore heterogeneity. Higher concentrations of residual brine are observed near the injection well in more heterogeneous porous media. Capillary backflow replenishes evaporative losses near the well during drying in hydrophilic chips. Brine clusters induced by gas injection connect through brine films and reconnect by capillary backflow. Two types of pore habits of salt precipitation are identified: bulk salt within brine clusters and aggregated salt at the air‐brine interface. Salt precipitation, particularly near the injection well, significantly reduces injectivity, with less impact observed in the porous media with uniform pore structure and hydrophobic surfaces.
Intellectual disability and autism in propionic acidemia: a biomarker-behavioral investigation implicating dysregulated mitochondrial biology
Authors: Shchelochkov Oleg A. , Farmer Cristan A. , Chlebowski Colby , Adedipe Dee , Ferry Susan , Manoli Irini , Pass Alexandra , McCoy Samantha , Van Ryzin Carol , Sloan Jennifer , Thurm Audrey , Venditti Charles P.
Published: January 2024

Propionic acidemia (PA) is an autosomal recessive condition (OMIM #606054), wherein pathogenic variants inPCCAandPCCBimpair the activity of propionyl-CoA carboxylase. PA is associated with neurodevelopmental disorders, including intellectual disability (ID) and autism spectrum disorder (ASD); however, the correlates and mechanisms of these outcomes remain unknown. Using data from a subset of participants with PA enrolled in a dedicated natural history study (n = 33), we explored associations between neurodevelopmental phenotypes and laboratory parameters. Twenty (61%) participants received an ID diagnosis, and 12 of the 31 (39%) who were fully evaluated received the diagnosis of ASD. A diagnosis of ID, lower full-scale IQ (sample mean = 65 ± 26), and lower adaptive behavior composite scores (sample mean = 67 ± 23) were associated with several biomarkers. Higher concentrations of plasma propionylcarnitine, plasma total 2-methylcitrate, serum erythropoietin, and mitochondrial biomarkers plasma FGF21 and GDF15 were associated with a more severe ID profile. Reduced 1-13C-propionate oxidative capacity and decreased levels of plasma and urinary glutamine were also associated with a more severe ID profile. Only two parameters, increased serum erythropoietin and decreased plasma glutamine, were associated with ASD. Plasma glycine, one of the defining features of PA, was not meaningfully associated with either ID or ASD. Thus, while both ID and ASD were commonly observed in our PA cohort, only ID was robustly associated with metabolic parameters. Our results suggest that disease severity and associated mitochondrial dysfunction may play a role in CNS complications of PA and identify potential biomarkers and candidate surrogate endpoints.
Translational implications of CHRFAM7A, an elusive human-restricted fusion gene
Authors: Ihnatovych Ivanna , Saddler Ruth-Ann , Sule Norbert , Szigeti Kinga
Published: January 2024

Genes restricted to humans may contribute to human-specific traits and provide a different context for diseases.CHRFAM7Ais a uniquely human fusion gene and a negative regulator of the α7 nicotinic acetylcholine receptor (α7 nAChR). The α7 nAChR has been a promising target for diseases affecting cognition and higher cortical functions, however, the treatment effect observed in animal models failed to translate into human clinical trials. AsCHRFAM7Awas not accounted for in preclinical drug screens it may have contributed to the translational gap. Understanding the complex genetic architecture of the locus, deciphering the functional impact of CHRFAM7A on α7 nAChR neurobiology and utilizing human-relevant models may offer novel approaches to explore α7 nAChR as a drug target.
Placental transcriptomic signatures of prenatal and preconceptional maternal stress
Authors: Baker Brennan H. , Freije Sophie , MacDonald James W. , Bammler Theo K. , Benson Ciara , Carroll Kecia N. , Enquobahrie Daniel A. , Karr Catherine J. , LeWinn Kaja Z. , Zhao Qi , Bush Nicole R. , Sathyanarayana Sheela , Paquette Alison G.
Published: January 2024

Prenatal exposure to maternal psychological stress is associated with increased risk for adverse birth and child health outcomes. Accumulating evidence suggests that preconceptional maternal stress may also be transmitted intergenerationally to negatively impact offspring. However, understanding of mechanisms linking these exposures to offspring outcomes, particularly those related to placenta, is limited. Using RNA sequencing, we identified placental transcriptomic signatures associated with maternal prenatal stressful life events (SLEs) and childhood traumatic events (CTEs) in 1 029 mother-child pairs in two birth cohorts from Washington state and Memphis, Tennessee. We evaluated individual gene-SLE/CTE associations and performed an ensemble of gene set enrichment analyses combing across 11 popular enrichment methods. Higher number of prenatal SLEs was significantly (FDR < 0.05) associated with increased expression of ADGRG6, a placental tissue-specific gene critical in placental remodeling, and decreased expression of RAB11FIP3, an endocytosis and endocytic recycling gene, and SMYD5, a histone methyltransferase. Prenatal SLEs and maternal CTEs were associated with gene sets related to several biological pathways, including upregulation of protein processing in the endoplasmic reticulum, protein secretion, and ubiquitin mediated proteolysis, and down regulation of ribosome, epithelial mesenchymal transition, DNA repair, MYC targets, and amino acid-related pathways. The directional associations in these pathways corroborate prior non-transcriptomic mechanistic studies of psychological stress and mental health disorders, and have previously been implicated in pregnancy complications and adverse birth outcomes. Accordingly, our findings suggest that maternal exposure to psychosocial stressors during pregnancy as well as the mother’s childhood may disrupt placental function, which may ultimately contribute to adverse pregnancy, birth, and child health outcomes.
Early prediction of pediatric asthma in the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort using machine learning
Authors: He Ping , Moraes Theo J. , Dai Darlene , Reyna-Vargas Myrtha E. , Dai Ruixue , Mandhane Piush , Simons Elinor , Azad Meghan B. , Hoskinson Courtney , Petersen Charisse , Del Bel Kate L. , Turvey Stuart E. , Subbarao Padmaja , Goldenberg Anna , Erdman Lauren
Published: January 2024

Background

Early identification of children at risk of asthma can have significant clinical implications for effective intervention and treatment. This study aims to disentangle the relative timing and importance of early markers of asthma.

Methods

Using the CHILD Cohort Study, 132 variables measured in 1754 multi-ethnic children were included in the analysis for asthma prediction. Data up to 4 years of age was used in multiple machine learning models to predict physician-diagnosed asthma at age 5 years. Both predictive performance and variable importance was assessed in these models.

Results

Early-life data (≤1 year) has limited predictive ability for physician-diagnosed asthma at age 5 years (area under the precision-recall curve (AUPRC) < 0.35). The earliest reliable prediction of asthma is achieved at age 3 years, (area under the receiver-operator curve (AUROC) > 0.90) and (AUPRC > 0.80). Maternal asthma, antibiotic exposure, and lower respiratory tract infections remained highly predictive throughout childhood. Wheezing status and atopy are the most important predictors of early childhood asthma from among the factors included in this study.

Conclusions

Childhood asthma is predictable from non-biological measurements from the age of 3 years, primarily using parental asthma and patient history of wheezing, atopy, antibiotic exposure, and lower respiratory tract infections.

Impact

Machine learning models can predict physician-diagnosed asthma in early childhood (AUROC > 0.90 and AUPRC > 0.80) using ≥3 years of non-biological and non-genetic information, whereas prediction with the same patient information available before 1 year of age is challenging.

Wheezing, atopy, antibiotic exposure, lower respiratory tract infections, and the child’s mother having asthma were the strongest early markers of 5-year asthma diagnosis, suggesting an opportunity for earlier diagnosis and intervention and focused assessment of patients at risk for asthma, with an evolving risk stratification over time.
Medical and genetic correlates of long-term buprenorphine treatment in the electronic health records
Authors: Niarchou Maria , Sanchez-Roige Sandra , Reddy India A. , Reese Thomas J. , Marcovitz David , Davis Lea K.
Published: January 2024

Despite the benefits associated with longer buprenorphine treatment duration (i.e., >180 days) (BTD) for opioid use disorder (OUD), retention remains poor. Research on the impact of co-occurring psychiatric issues on BTD has yielded mixed results. It is also unknown whether the genetic risk in the form of polygenic scores (PGS) for OUD and other comorbid conditions, including problematic alcohol use (PAU) are associated with BTD. We tested the association between somatic and psychiatric comorbidities and long BTD and determined whether PGS for OUD-related conditions was associated with BTD. The study included 6686 individuals with a buprenorphine prescription that lasted for less than 6 months (short-BTD) and 1282 individuals with a buprenorphine prescription that lasted for at least 6 months (long-BTD). Recorded diagnosis of substance addiction and disorders (Odds Ratio (95% CI) = 22.14 (21.88–22.41), P = 2.8 × 10−116), tobacco use disorder (OR (95% CI) = 23.4 (23.13–23.68), P = 4.5 × 10−111), and bipolar disorder (OR(95% CI) = 9.70 (9.48–9.92), P = 1.3 × 10−91), among others, were associated with longer BTD. The PGS of OUD and several OUD co-morbid conditions were associated with any buprenorphine prescription. A higher PGS for OUD (OR per SD increase in PGS (95%CI) = 1.43(1.16–1.77), P = 0.0009), loneliness (OR(95% CI) = 1.39(1.13–1.72), P = 0.002), problematic alcohol use (OR(95%CI) = 1.47(1.19–1.83), P = 0.0004), and externalizing disorders (OR(95%CI) = 1.52(1.23 to 1.89), P = 0.0001) was significantly associated with long-BTD. Associations between BTD and the PGS of depression, chronic pain, nicotine dependence, cannabis use disorder, and bipolar disorder did not survive correction for multiple testing. Longer BTD is associated with diagnoses of psychiatric and somatic conditions in the EHR, as is the genetic score for OUD, loneliness, problematic alcohol use, and externalizing disorders.
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

Antipsychotic (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

Granulocyte 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

ASPP1 (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

Intestinal 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

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

Lithium-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

Cryo-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

Cellular 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

The 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

Bioisosteric 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

Carbon 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

Electro-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

The 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

Parkinson’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.
Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2
Authors: Yin Kailin , Peluso Michael J. , Luo Xiaoyu , Thomas Reuben , Shin Min-Gyoung , Neidleman Jason , Andrew Alicer , Young Kyrlia C. , Ma Tongcui , Hoh Rebecca , Anglin Khamal , Huang Beatrice , Argueta Urania , Lopez Monica , Valdivieso Daisy , Asare Kofi , Deveau Tyler-Marie , Munter Sadie E. , Ibrahim Rania , Ständker Ludger , Lu Scott , Goldberg Sarah A. , Lee Sulggi A. , Lynch Kara L. , Kelly J. Daniel , Martin Jeffrey N. , Münch Jan , Deeks Steven G. , Henrich Timothy J. , Roan Nadia R.
Published: January 2024

Long COVID (LC) occurs after at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, yet its etiology remains poorly understood. We used ‘omic” assays and serology to deeply characterize the global and SARS-CoV-2-specific immunity in the blood of individuals with clear LC and non-LC clinical trajectories, 8 months postinfection. We found that LC individuals exhibited systemic inflammation and immune dysregulation. This was evidenced by global differences in T cell subset distribution implying ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. LC individuals displayed increased frequencies of CD4+T cells poised to migrate to inflamed tissues and exhausted SARS-CoV-2-specific CD8+T cells, higher levels of SARS-CoV-2 antibodies and a mis-coordination between their SARS-CoV-2-specific T and B cell responses. Our analysis suggested an improper crosstalk between the cellular and humoral adaptive immunity in LC, which can lead to immune dysregulation, inflammation and clinical symptoms associated with this debilitating condition.
Insights for precision oncology from the integration of genomic and clinical data of 13,880 tumors from the 100,000 Genomes Cancer Programme
Authors: Sosinsky Alona , Ambrose John , Cross William , Turnbull Clare , Henderson Shirley , Jones Louise , Hamblin Angela , Arumugam Prabhu , Chan Georgia , Chubb Daniel , Noyvert Boris , Mitchell Jonathan , Walker Susan , Bowman Katy , Pasko Dorota , Buongermino Pereira Marianna , Volkova Nadezda , Rueda-Martin Antonio , Perez-Gil Daniel , Lopez Javier , Pullinger John , Siddiq Afshan , Zainy Tala , Choudhury Tasnim , Yavorska Olena , Fowler Tom , Bentley David , Kingsley Clare , Hing Sandra , Deans Zandra , Rendon Augusto , Hill Sue , Caulfield Mark , Murugaesu Nirupa
Published: January 2024

The Cancer Programme of the 100,000 Genomes Project was an initiative to provide whole-genome sequencing (WGS) for patients with cancer, evaluating opportunities for precision cancer care within the UK National Healthcare System (NHS). Genomics England, alongside NHS England, analyzed WGS data from 13,880 solid tumors spanning 33 cancer types, integrating genomic data with real-world treatment and outcome data, within a secure Research Environment. Incidence of somatic mutations in genes recommended for standard-of-care testing varied across cancer types. For instance, in glioblastoma multiforme, small variants were present in 94% of cases and copy number aberrations in at least one gene in 58% of cases, while sarcoma demonstrated the highest occurrence of actionable structural variants (13%). Homologous recombination deficiency was identified in 40% of high-grade serous ovarian cancer cases with 30% linked to pathogenic germline variants, highlighting the value of combined somatic and germline analysis. The linkage of WGS and longitudinal life course clinical data allowed the assessment of treatment outcomes for patients stratified according to pangenomic markers. Our findings demonstrate the utility of linking genomic and real-world clinical data to enable survival analysis to identify cancer genes that affect prognosis and advance our understanding of how cancer genomics impacts patient outcomes.
Revealing the quantum nature of the voltage-induced conductance changes in oxygen engineered yttrium oxide-based RRAM devices
Authors: Aguirre F. L. , Piros E. , Kaiser N. , Vogel T. , Petzold S. , Gehrunger J. , Hochberger C. , Oster T. , Hofmann K. , Suñé J. , Miranda E. , Alff L.
Published: January 2024

In this work, the quasi-analog to discrete transition occurring in the current–voltage characteristic of oxygen engineered yttrium oxide-based resistive random-access memory (RRAM) devices is investigated in detail. In particular, the focus of our research is not on the absolute conductance values of this characteristic but on the magnitude of its conductance changes occurring during the reset process of the device. It is found that the detected changes correspond to conductance values predominantly of the order of the quantum unit of conductance G0 = 2e2/h, where e is the electron charge and h the Planck constant. This feature is observed even at conductance levels far above G0, i.e. where electron transport is seemingly diffusive. It is also observed that such behavior is reproducible across devices comprising yttrium oxide layers with different oxygen concentrations and measured under different voltage sweep rates. While the oxygen deficiency affects the total number of quantized conductance states, the magnitude of the changes in conductance, close to 1 G0, is invariant to the oxygen content of the functional layer.
Breaking barriers in Candida spp. detection with Electronic Noses and artificial intelligence
Authors: Bastos Michael L. , Benevides Clayton A. , Zanchettin Cleber , Menezes Frederico D. , Inácio Cícero P. , de Lima Neto Reginaldo G. , Filho José Gilson A. T. , Neves Rejane P. , Almeida Leandro M.
Published: January 2024

The timely and accurate diagnosis of candidemia, a severe bloodstream infection caused byCandidaspp., remains challenging in clinical practice. Blood culture, the current gold standard technique, suffers from lengthy turnaround times and limited sensitivity. To address these limitations, we propose a novel approach utilizing an Electronic Nose (E-nose) combined with Time Series-based classification techniques to analyze and identifyCandidaspp. rapidly, using culture species of C.albicans, C.kodamaea ohmeri, C.glabrara, C.haemulonii, C.parapsilosisand C.kruseias control samples. This innovative method not only enhances diagnostic accuracy and reduces decision time for healthcare professionals in selecting appropriate treatments but also offers the potential for expanded usage and cost reduction due to the E-nose’s low production costs. Our proof-of-concept experimental results, carried out with culture samples, demonstrate promising outcomes, with the Inception Time classifier achieving an impressive average accuracy of 97.46% during the test phase. This paper presents a groundbreaking advancement in the field, empowering medical practitioners with an efficient and reliable tool for early and precise identification of candidemia, ultimately leading to improved patient outcomes.
The effect of Israeli acute paralysis virus infection on honey bee brood care behavior
Authors: Taylor Lincoln N. , Dolezal Adam G.
Published: January 2024

To protect themselves from communicable diseases, social insects utilize social immunity—behavioral, physiological, and organizational means to combat disease transmission and severity. Within a honey bee colony, larvae are visited thousands of times by nurse bees, representing a prime environment for pathogen transmission. We investigated a potential social immune response to Israeli acute paralysis virus (IAPV) infection in brood care, testing the hypotheses that bees will respond with behaviors that result in reduced brood care, or that infection results in elevated brood care as a virus-driven mechanism to increase transmission. We tested for group-level effects by comparing three different social environments in which 0%, 50%, or 100% of nurse bees were experimentally infected with IAPV. We investigated individual-level effects by comparing exposed bees to unexposed bees within the mixed-exposure treatment group. We found no evidence for a social immune response at the group level; however, individually, exposed bees interacted with the larva more frequently than their unexposed nestmates. While this could increase virus transmission from adults to larvae, it could also represent a hygienic response to increase grooming when an infection is detected. Together, our findings underline the complexity of disease dynamics in complex social animal systems.
Racial Discrimination and Administrative Burden in Access to Public Services
Authors: Bell Elizabeth , Jilke Sebastian
Published: January 2024

Equal access to public services is a foundational element of democratic societies. Yet, stark inequalities in access to public services persist, partially due to bureaucratic discrimination, or differential treatment by bureaucrats. This study investigates the causal mechanism of bureaucratic discrimination, arguing that racial discrimination can serve as a means of cream skimming, when there are economic incentives to prioritize easier-to-serve clientele. We predict that in the absence of information regarding prospective clients’ performance, group-level performance information will be imposed on racially minoritized individuals. We implemented a nationwide email correspondence audit experiment including all charter school principals in the U.S. (n = 5850). The findings show that Black email aliases faced significantly higher administrative burdens in trying to get access to charter schools than White email aliases when no performance signal was provided. However, when a direct signal of clients’ performance was introduced, the racial disparities diminished. Overall, these results provide evidence on the causal mechanism of bureaucratic discrimination as a means of cream-skimming.
Human robotic surgery with intraoperative tissue identification using rapid evaporation ionisation mass spectrometry
Authors: Manoli Eftychios , Higginson James , Tolley Neil , Darzi Ara , Kinross James , Temelkuran Burak , Takats Zoltan
Published: January 2024

Instantaneous, continuous, and reliable information on the molecular biology of surgical target tissue could significantly contribute to the precision, safety, and speed of the intervention. In this work, we introduced a methodology for chemical tissue identification in robotic surgery using rapid evaporative ionisation mass spectrometry. We developed a surgical aerosol evacuation system that is compatible with a robotic platform enabling consistent intraoperative sample collection and assessed the feasibility of this platform during head and neck surgical cases, using two different surgical energy devices. Our data showed specific, characteristic lipid profiles associated with the tissue type including various ceramides, glycerophospholipids, and glycerolipids, as well as different ion formation mechanisms based on the energy device used. This platform allows continuous and accurate intraoperative mass spectrometry-based identification of ablated/resected tissue and in combination with robotic registration of images, time, and anatomical positions can improve the current robot-assisted surgical platforms and guide surgical strategy.
New inorganic inhibitors derived from cefotaxime to enhance corrosion resistance of mild steel in 3% NaCl
Authors: Abd El-Zahir Mustafa S. , Soliman Mohamed H. A. , ELKady Hamdy A. , El-Sakka Sahar S. A. , Orabi Adel S.
Published: January 2024

To overcome the threat of corrosion and its cost, a new Schiff base was prepared and utilized to synthesize inorganic inhibitors to enhance corrosion resistance and reduce current density. The Schiff base was obtained from the interaction of cefotaxime with acetylacetone, while 1H NMR and IR spectra were used to confirm the preparation. Moreover, FeIII, CoII, NiII and CuII metal salts were reacted with the Schiff base to give the corresponding complexes. Meanwhile, the non-ionic behavior of the observed complexes in solutions was proved from the conductance results. In addition, the octahedral geometry and the postulated structure of complexes were determined from CHNM%, IR spectroscopy, UV-visible spectra, and TGA analysis. Also, the energy of molecular orbitals (HOMO and LUMO) and other quantum mechanics parameters were calculated using the DFT method. The observed results indicated the reactivity of metal complexes and their ability to donate electrons more than the Schiff base. Furthermore, the corrosion rate of a steel sample under various concentrations of inhibitors was calculated by a potentiodynamic polarization test. The obtained data displayed that metal complexes declined the corrosion rate more than the Schiff base; therefore, the binding between the metal ion and the Schiff base improved the inhibition efficiency.