bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep reaction network exploration at a heterogeneous catalytic interface
Authors: Zhao Qiyuan , Xu Yinan , Greeley Jeffrey , Savoie Brett M. 
Published: August 2022

AbstractCharacterizing the reaction energies and barriers of reaction networks is central to catalyst development. However, heterogeneous catalytic surfaces pose several unique challenges to automatic reaction network characterization, including large sizes and open-ended reactant sets, that make ad hoc network construction the current state-of-the-art. Here, we show how automated network exploration algorithms can be adapted to the constraints of heterogeneous systems using ethylene oligomerization on silica-supported single-site Ga3+ as a model system. Using only graph-based rules for exploring the network and elementary constraints based on activation energy and size for identifying network terminations, a comprehensive reaction network is generated and validated against standard methods. The algorithm (re)discovers the Ga-alkyl-centered Cossee-Arlman mechanism that is hypothesized to drive major product formation while also predicting several new pathways for producing alkanes and coke precursors. These results demonstrate that automated reaction exploration algorithms are rapidly maturing towards general purpose capability for exploratory catalytic applications.
Phase-locked constructing dynamic supramolecular ionic conductive elastomers with superior toughness, autonomous self-healing and recyclability
Authors: Chen Jing , Gao Yiyang , Shi Lei , Yu Wei , Sun Zongjie , Zhou Yifan , Liu Shuang , Mao Heng , Zhang Dongyang , Lu Tongqing , Chen Quan , Yu Demei , Ding Shujiang 
Published: August 2022

AbstractStretchable ionic conductors are considerable to be the most attractive candidate for next-generation flexible ionotronic devices. Nevertheless, high ionic conductivity, excellent mechanical properties, good self-healing capacity and recyclability are necessary but can be rarely satisfied in one material. Herein, we propose an ionic conductor design, dynamic supramolecular ionic conductive elastomers (DSICE), via phase-locked strategy, wherein locking soft phase polyether backbone conducts lithium-ion (Li+) transport and the combination of dynamic disulfide metathesis and stronger supramolecular quadruple hydrogen bonds in the hard domains contributes to the self-healing capacity and mechanical versatility. The dual-phase design performs its own functions and the conflict among ionic conductivity, self-healing capability, and mechanical compatibility can be thus defeated. The well-designed DSICE exhibits high ionic conductivity (3.77 × 10−3 S m−1 at 30 °C), high transparency (92.3%), superior stretchability (2615.17% elongation), strength (27.83 MPa) and toughness (164.36 MJ m−3), excellent self-healing capability (~99% at room temperature) and favorable recyclability. This work provides an interesting strategy for designing the advanced ionic conductors and offers promise for flexible ionotronic devices or solid-state batteries.
Predicting response to immunotherapy in gastric cancer via multi-dimensional analyses of the tumour immune microenvironment
Authors: Chen Yang , Jia Keren , Sun Yu , Zhang Cheng , Li Yilin , Zhang Li , Chen Zifan , Zhang Jiangdong , Hu Yajie , Yuan Jiajia , Zhao Xingwang , Li Yanyan , Gong Jifang , Dong Bin , Zhang Xiaotian , Li Jian , Shen Lin 
Published: August 2022

AbstractA single biomarker is not adequate to identify patients with gastric cancer (GC) who have the potential to benefit from anti-PD-1/PD-L1 therapy, presumably owing to the complexity of the tumour microenvironment. The predictive value of tumour-infiltrating immune cells (TIICs) has not been definitively established with regard to their density and spatial organisation. Here, multiplex immunohistochemistry is used to quantify in situ biomarkers at sub-cellular resolution in 80 patients with GC. To predict the response to immunotherapy, we establish a multi-dimensional TIIC signature by considering the density of CD4+FoxP3−PD-L1+, CD8+PD-1−LAG3−, and CD68+STING+ cells and the spatial organisation of CD8+PD-1+LAG3− T cells. The TIIC signature enables prediction of the response of patients with GC to anti-PD-1/PD-L1 immunotherapy and patient survival. Our findings demonstrate that a multi-dimensional TIIC signature may be relevant for the selection of patients who could benefit the most from anti-PD-1/PD-L1 immunotherapy.
Heterogenous humoral and cellular immune responses with distinct trajectories post-SARS-CoV-2 infection in a population-based cohort
Authors: Menges Dominik , Zens Kyra D. , Ballouz Tala , Caduff Nicole , Llanas-Cornejo Daniel , Aschmann Hélène E. , Domenghino Anja , Pellaton Céline , Perreau Matthieu , Fenwick Craig , Pantaleo Giuseppe , Kahlert Christian R. , Münz Christian , Puhan Milo A. , Fehr Jan S. 
Published: August 2022

AbstractTo better understand the development of SARS-CoV-2-specific immunity over time, a detailed evaluation of humoral and cellular responses is required. Here, we characterize anti-Spike (S) IgA and IgG in a representative population-based cohort of 431 SARS-CoV-2-infected individuals up to 217 days after diagnosis, demonstrating that 85% develop and maintain anti-S responses. In a subsample of 64 participants, we further assess anti-Nucleocapsid (N) IgG, neutralizing antibody activity, and T cell responses to Membrane (M), N, and S proteins. In contrast to S-specific antibody responses, anti-N IgG levels decline substantially over time and neutralizing activity toward Delta and Omicron variants is low to non-existent within just weeks of Wildtype SARS-CoV-2 infection. Virus-specific T cells are detectable in most participants, albeit more variable than antibody responses. Cluster analyses of the co-evolution of antibody and T cell responses within individuals identify five distinct trajectories characterized by specific immune patterns and clinical factors. These findings demonstrate the relevant heterogeneity in humoral and cellular immunity to SARS-CoV-2 while also identifying consistent patterns where antibody and T cell responses may work in a compensatory manner to provide protection.
Structural basis for cannabinoid-induced potentiation of alpha1-glycine receptors in lipid nanodiscs
Authors: Kumar Arvind , Kindig Kayla , Rao Shanlin , Zaki Afroditi-Maria , Basak Sandip , Sansom Mark S. P. , Biggin Philip C. , Chakrapani Sudha 
Published: August 2022

AbstractNociception and motor coordination are critically governed by glycine receptor (GlyR) function at inhibitory synapses. Consequentially, GlyRs are attractive targets in the management of chronic pain and in the treatment of several neurological disorders. High-resolution mechanistic details of GlyR function and its modulation are just emerging. While it has been known that cannabinoids such as Δ9-tetrahydrocannabinol (THC), the principal psychoactive constituent in marijuana, potentiate GlyR in the therapeutically relevant concentration range, the molecular mechanism underlying this effect is still not understood. Here, we present Cryo-EM structures of full-length GlyR reconstituted into lipid nanodisc in complex with THC under varying concentrations of glycine. The GlyR-THC complexes are captured in multiple conformational states that reveal the basis for THC-mediated potentiation, manifested as different extents of opening at the level of the channel pore. Taken together, these structural findings, combined with molecular dynamics simulations and functional analysis, provide insights into the potential THC binding site and the allosteric coupling to the channel pore.
Achieving thermally stable nanoparticles in chemically complex alloys via controllable sluggish lattice diffusion
Authors: Xiao Bo , Luan Junhua , Zhao Shijun , Zhang Lijun , Chen Shiyao , Zhao Yilu , Xu Lianyong , Liu C. T. , Kai Ji-Jung , Yang Tao 
Published: August 2022

AbstractNanoparticle strengthening provides a crucial basis for developing high-performance structural materials with potentially superb mechanical properties for structural applications. However, the general wisdom often fails to work well due to the poor thermal stability of nanoparticles, and the rapid coarsening of these particles will lead to the accelerated failures of these materials especially at elevated temperatures. Here, we demonstrate a strategy to achieve ultra-stable nanoparticles at 800~1000 °C in a Ni59.9-xCoxFe13Cr15Al6Ti6B0.1 (at.%) chemically complex alloy, resulting from the controllable sluggish lattice diffusion (SLD) effect. Our diffusion kinetic simulations reveal that the Co element leads to a significant reduction in the interdiffusion coefficients of all the main elements, especially for the Al element, with a maximum of up to 5 orders of magnitude. Utilizing first-principles calculations, we further unveil the incompressibility of Al induced by the increased concentration of Co plays a critical role in controlling the SLD effect. These findings are useful for providing advances in the design of novel structural alloys with extraordinary property-microstructure stability combinations for structural applications.
Ano5 modulates calcium signaling during bone homeostasis in gnathodiaphyseal dysplasia
Authors: Li Xin , Wang Lei , Wang Hongwei , Qin An , Qin Xingjun 
Published: August 2022

AbstractANO5 encodes transmembrane protein 16E (TMEM16E), an intracellular calcium-activated chloride channel in the endoplasmic reticulum. Mutations in ANO5 are associated with gnathodiaphyseal dysplasia (GDD), a skeletal disorder causing the jaw deformity and long bone fractures. However, the coordinated mechanism by which ANO5 mediates bone homeostasis in GDD remains poorly defined. Here, we show that ablation of Ano5 reduced intracellular calcium transients, leading to defects in osteogenesis and osteoclastogenesis and thus bone dysplasia. We found a causative de novo ANO5 frameshift insertion mutation (p.L370_A371insDYWRLNSTCL) in a GDD family with osteopenia, accompanied by a decrease in TMEM16E expression and impaired RANKL-induced intracellular calcium ([Ca2+]i) oscillations in osteoclasts. Moreover, using Ano5 knockout (KO) mice, we found that they exhibited low bone volume, abnormal calcium deposits, and defective osteoblast and osteoclast differentiation. We also showed that Ano5 deletion in mice significantly diminished [Ca2+]i oscillations in both osteoblasts and osteoclasts, which resulted in reduced WNT/β-Catenin and RANKL-NFATc1 signaling, respectively. Osteoanabolic treatment of parathyroid hormone was effective in enhancing bone strength in Ano5 KO mice. Consequently, these data demonstrate that Ano5 positively modulates bone homeostasis via calcium signaling in GDD.
Characterization of interactions of dietary cholesterol with the murine and human gut microbiome
Authors: Le Henry H. , Lee Min-Ting , Besler Kevin R. , Comrie Janine M. C. , Johnson Elizabeth L. 
Published: August 2022

AbstractConsumption of dietary lipids, such as cholesterol, modulates the gut microbiome with consequences for host health through the production of microbiome-derived metabolites. Despite the implications for host metabolism, a limited number of specific interactions of the gut microbiome with diet-derived lipids have been characterized. This is partially because obtaining species-level resolution of the responsible taxa can be challenging and additional approaches are needed to identify health-relevant metabolites produced from cholesterol–microbiome interactions. Here we performed bio-orthogonal labelling sort sequence spectrometry, a click chemistry based workflow, to profile cholesterol-specific host–microbe interactions. Mice were exposed to an alkyne-functionalized variant of cholesterol and 16S ribosomal RNA gene amplicon sequencing of faecal samples identified diet-derived cholesterol-interacting microbes from the genera Bacteroides, Bifidobacterium, Enterococcus and Parabacteroides. Shotgun metagenomic analysis provided species-level resolution of diet-derived cholesterol-interacting microbes with enrichment of bile acid-like and sulfotransferase-like activities. Using untargeted metabolomics, we identify that cholesterol is converted to cholesterol sulfate in a Bacteroides-specific manner via the enzyme BT_0416. Mice monocolonized with Bacteroides thetaiotaomicron lacking Bt_0416 showed altered host cholesterol and cholesterol sulfate compared with wild-type mice, identifying a previously uncharacterized microbiome-transformation of cholesterol and a mechanism for microbiome-dependent contributions to host phenotype. Moreover, identification of a cholesterol-responsive sulfotransferase in Bacteroides suggests diet-dependent mechanisms for altering microbiome-specific cholesterol metabolism. Overall, our work identifies numerous cholesterol-interacting microbes with implications for more precise microbiome-conscious regulation of host cholesterol homeostasis.
Percutaneous transluminal angioplasty for symptomatic hepatic vein-type Budd-Chiari syndrome: feasibility and long-term outcomes
Authors: Elkilany Aboelyazid , Alwarraky Mohamed , Denecke Timm , Geisel Dominik 
Published: August 2022

AbstractFor management of Budd-Chiari syndrome (BCS), a step-wise therapeutic approach starting with medical treatment, followed by endovascular recanalization, transjugular intrahepatic portosystemic shunt, and finally liver transplantation has been adopted. We retrospectively analyzed 51 patients with symptomatic short segment (≤ 30 mm) hepatic vein (HV)-type BCS who underwent percutaneous transluminal balloon angioplasty (PTBA) with/without stenting to determine the feasibility, clinical effectiveness, and long-term outcomes. The intervention was technically successful in 94.1% of cases (48/51)—32 patients underwent PTBA and 16 patients underwent HV stenting. Procedure-related complications occurred in 14 patients (29.1%). The clinical success rate at 4 weeks was 91.7% (44/48). Nine patients underwent reintervention, six patients due to restenosis/occlusion and three patients with clinical failure. The mean primary patency duration was 64.6 ± 19.9 months (CI, 58.5–70.8; range, 1.2–81.7 months). The cumulative 1-, 2-, and 5-year primary patency rates were 85.4, 74.5, and 58.3%, respectively. The cumulative 1-, 2-, and 5-year secondary patency rates were 93.8, 87.2, and 75%, respectively. The cumulative 1-, 2-, and 5-year survival rates were 97.9, 91.5, and 50%, respectively. Percutaneous transluminal angioplasty with and without stenting is effective and achieves excellent long-term patency and survival rates in patients with symptomatic HV-type BCS. With its lower incidence of re-occlusion and higher clinical success rate, HV angioplasty combined with stenting should be the preferred option especially in patients with segmental HV-type BCS.
Novel covalent and non-covalent complex-based pharmacophore models of SARS-CoV-2 main protease (Mpro) elucidated by microsecond MD simulations
Authors: Hayek-Orduz Yasser , Vásquez Andrés Felipe , Villegas-Torres María Francisca , Caicedo Paola A. , Achenie Luke E. K. , González Barrios Andrés Fernando 
Published: August 2022

AbstractAs the world enters its second year of the pandemic caused by SARS-CoV-2, intense efforts have been directed to develop an effective diagnosis, prevention, and treatment strategies. One promising drug target to design COVID-19 treatments is the SARS-CoV-2 Mpro. To date, a comparative understanding of Mprodynamic stereoelectronic interactions with either covalent or non-covalent inhibitors (depending on their interaction with a pocket called S1’ or oxyanion hole) has not been still achieved. In this study, we seek to fill this knowledge gap using a cascade in silico protocol of docking, molecular dynamics simulations, and MM/PBSA in order to elucidate pharmacophore models for both types of inhibitors. After docking and MD analysis, a set of complex-based pharmacophore models was elucidated for covalent and non-covalent categories making use of the residue bonding point feature. The highest ranked models exhibited ROC-AUC values of 0.93 and 0.73, respectively for each category. Interestingly, we observed that the active site region of Mproprotein–ligand complex undergoes large conformational changes, especially within the S2 and S4 subsites. The results reported in this article may be helpful in virtual screening (VS) campaigns to guide the design and discovery of novel small-molecule therapeutic agents against SARS-CoV-2 Mproprotein.
Feeding ecology of the endangered Asiatic wild dogs (Cuon alpinus) across tropical forests of the Central Indian Landscape
Authors: Ghaskadbi Pallavi , Bathla Neetu , Bhandari Aishwarya , Modi Shrushti , Nigam Parag , Habib Bilal 
Published: August 2022

AbstractStudies on resource utilisation by carnivores are essential as they aid in assessing their role in a community, by unravelling predator–prey relationships. Globally, prey depletion is one of the primary causes of declining Asiatic wild dog (dhole) populations. Therefore, it is essential to examine their diet across their range. Our study presents insights into dhole feeding ecology across multiple sites from the central Indian landscape of Maharashtra, India, for the first time. We conducted scat analysis using a subset of genetically identified scats and collected additional data from kills observed while tracking radio-collared dholes and other known packs from 2 study sites. We analysed 861 scats, and 191 dhole kills to identify species and age class of prey. We estimated the relative contribution of various prey, utilising non-linear biomass models of prey consumption. Overall, wild ungulates like sambar and chital were the principal prey in terms of biomass (sambar 61.08%; chital 19.08%) and number of prey consumed (sambar 39.28%; chital 13.83%). An analysis of kill data also suggested that dholes strongly preferred the two deer species; and differential selection of age classes was observed at the 2 study sites. Our study can potentially help manage and conserve this important population of an endangered carnivore.
Structural characterization and antibacterial activity of silver nanoparticles synthesized using a low-molecular-weight Royal Jelly extract
Authors: Gevorgyan Susanna , Schubert Robin , Falke Sven , Lorenzen Kristina , Trchounian Karen , Betzel Christian 
Published: August 2022

AbstractIn recent years silver nanoparticles (Ag NPs) gained increased and widespread applications in various fields of industry, technology, and medicine. This study describes the green synthesis of silver nanoparticles (Ag NPs) applying a low-molecular-weight fraction (LMF) of Royal Jelly, the nanoparticle characterization, and particularly their antibacterial activity. The optical properties of NPs, characterized by UV–Vis absorption spectroscopy, showed a peak at ~ 430 nm. The hydrodynamic radius and concentration were determined by complementary dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). The particle morphology was investigated using transmission electron microscopy (TEM), and the crystallinity of the silver was confirmed by X-ray diffraction (XRD). The antibacterial activities were evaluated utilizing Gram-negative and Gram-positive bacteria and colony counting assays. The growth inhibition curve method was applied to obtain information about the corresponding minimum inhibitory concentrations (MIC) and the minimum bactericidal concentrations (MBC) required. Obtained results showed that (i) the sizes of Ag NPs are increasing within the increase of silver ion precursor concentration, (ii) DLS, in agreement with NTA, showed that most particles have dimensions in the range of 50–100 nm; (iii) E. coli was more susceptible to all Ag NP samples compared to B. subtilis.
Association of extracellular vesicle inflammatory proteins and mortality
Authors: Noren Hooten Nicole , Torres Stephanie , Mode Nicolle A. , Zonderman Alan B. , Ghosh Paritosh , Ezike Ngozi , Evans Michele K. 
Published: August 2022

AbstractEven before the COVID-19 pandemic declines in life expectancy in the United States were attributed to increased mortality rates in midlife adults across racial and ethnic groups, indicating a need for markers to identify individuals at risk for early mortality. Extracellular vesicles (EVs) are small, lipid-bound vesicles capable of shuttling functional proteins, nucleic acids, and lipids. Given their role as intercellular communicators and potential biomarkers of disease, we explored whether circulating EVs may be markers of mortality in a prospective, racially, and socioeconomically diverse middle-aged cohort. We isolated plasma EVs from 76 individuals (mean age = 59.6 years) who died within a 5 year period and 76 surviving individuals matched by age, race, and poverty status. There were no significant differences in EV concentration, size, or EV-associated mitochondrial DNA levels associated with mortality. We found that several EV-associated inflammatory proteins including CCL23, CSF-1, CXCL9, GDNF, MCP-1, STAMBP, and 4E-BP1 were significantly associated with mortality. IL-10RB and CDCP1 were more likely to be present in plasma EVs from deceased individuals than in their alive counterparts. We also report differences in EV-associated inflammatory proteins with poverty status, race, and sex. Our results suggest that plasma EV-associated inflammatory proteins are promising potential clinical biomarkers of mortality.
Real-time single-pixel imaging using a system on a chip field-programmable gate array
Authors: Hoshi Ikuo , Shimobaba Tomoyoshi , Kakue Takashi , Ito Tomoyoshi 
Published: August 2022

AbstractUnlike conventional imaging, the single-pixel imaging technique uses a single-element detector, which enables high sensitivity, broad wavelength, and noise robustness imaging. However, it has several challenges, particularly requiring extensive computations for image reconstruction with high image quality. Therefore, high-performance computers are required for real-time reconstruction with higher image quality. In this study, we developed a compact dedicated computer for single-pixel imaging using a system on a chip field-programmable gate array (FPGA), which enables real-time reconstruction at 40 frames per second with an image size of 128 × 128 pixels. An FPGA circuit was implemented with the proposed reconstruction algorithm to obtain higher image quality by introducing encoding mask pattern optimization. The dedicated computer can accelerate the reconstruction 10 times faster than a recent CPU. Because it is very compact compared with typical computers, it can expand the application of single-pixel imaging to the Internet of Things and outdoor applications.
Cognitive flexibility supports the development of cumulative cultural learning in children
Authors: Davis Sarah , Rawlings Bruce , Clegg Jennifer M. , Ikejimba Daniel , Watson-Jones Rachel E. , Whiten Andrew , Legare Cristine H. 
Published: August 2022

AbstractThe scale of cumulative cultural evolution (CCE) is a defining characteristic of humans. Despite marked scientific interest in CCE, the cognitive underpinnings supporting its development remain understudied. We examined the role cognitive flexibility plays in CCE by studying U.S. children’s (N = 167, 3–5-year-olds) propensity to relinquish an inefficient solution to a problem in favor of a more efficient alternative, and whether they would resist reverting to earlier versions. In contrast to previous work with chimpanzees, most children who first learned to solve a puzzlebox in an inefficient way switched to an observed, more efficient alternative. However, over multiple task interactions, 85% of children who switched reverted to the inefficient method. Moreover, almost all children in a control condition (who first learned the efficient method) switched to the inefficient method. Thus, children were keen to explore an alternative solution but, like chimpanzees, are overall conservative in reverting to their first-learned one.