bluuebunny/crossref_metadata_2025 huggingface dataset:
GLP-1R signaling neighborhoods associate with the susceptibility to adverse drug reactions of incretin mimetics
Authors: Wright Shane C. , Motso Aikaterini , Koutsilieri Stefania , Beusch Christian M. , Sabatier Pierre , Berghella Alessandro , Blondel-Tepaz Élodie , Mangenot Kimberley , Pittarokoilis Ioannis , Sismanoglou Despoina-Christina , Le Gouill Christian , Olsen Jesper V. , Zubarev Roman A. , Lambert Nevin A. , Hauser Alexander S. , Bouvier Michel , Lauschke Volker M.
Published: October 2023

G protein-coupled receptors are important drug targets that engage and activate signaling transducers in multiple cellular compartments. Delineating therapeutic signaling from signaling associated with adverse events is an important step towards rational drug design. The glucagon-like peptide-1 receptor (GLP-1R) is a validated target for the treatment of diabetes and obesity, but drugs that target this receptor are a frequent cause of adverse events. Using recently developed biosensors, we explored the ability of GLP-1R to activate 15 pathways in 4 cellular compartments and demonstrate that modifications aimed at improving the therapeutic potential of GLP-1R agonists greatly influence compound efficacy, potency, and safety in a pathway- and compartment-selective manner. These findings, together with comparative structure analysis, time-lapse microscopy, and phosphoproteomics, reveal unique signaling signatures for GLP-1R agonists at the level of receptor conformation, functional selectivity, and location bias, thus associating signaling neighborhoods with functionally distinct cellular outcomes and clinical consequences.
The Personalized Nutrition Study (POINTS): evaluation of a genetically informed weight loss approach, a Randomized Clinical Trial
Authors: Höchsmann Christoph , Yang Shengping , Ordovás José M. , Dorling James L. , Champagne Catherine M. , Apolzan John W. , Greenway Frank L. , Cardel Michelle I. , Foster Gary D. , Martin Corby K.
Published: October 2023

Weight loss (WL) differences between isocaloric high-carbohydrate and high-fat diets are generally small; however, individual WL varies within diet groups. Genotype patterns may modify diet effects, with carbohydrate-responsive genotypes losing more weight on high-carbohydrate diets (and vice versa for fat-responsive genotypes). We investigated whether 12-week WL (kg, primary outcome) differs between genotype-concordant and genotype-discordant diets. In this 12-week single-center WL trial, 145 participants with overweight/obesity were identified a priori as fat-responders or carbohydrate-responders based on their combined genotypes at ten genetic variants and randomized to a high-fat (n = 73) or high-carbohydrate diet (n = 72), yielding 4 groups: (1) fat-responders receiving high-fat diet, (2) fat-responders receiving high-carbohydrate diet, (3) carbohydrate-responders receiving high-fat diet, (4) carbohydrate-responders receiving high-carbohydrate diet. Dietitians delivered the WL intervention via 12 weekly diet-specific small group sessions. Outcome assessors were blind to diet assignment and genotype patterns. We included 122 participants (54.4 [SD:13.2] years, BMI 34.9 [SD:5.1] kg/m2, 84% women) in the analyses. Twelve-week WL did not differ between the genotype-concordant (−5.3 kg [SD:1.0]) and genotype-discordant diets (−4.8 kg [SD:1.1]; adjusted difference: −0.6 kg [95% CI: −2.1,0.9], p = 0.50). With the current ability to genotype participants as fat- or carbohydrate-responders, evidence does not support greater WL on genotype-concordant diets. ClinicalTrials identifier: NCT04145466.
Induced photoelectron circular dichroism onto an achiral chromophore
Authors: Rouquet Etienne , Roy Chowdhury Madhusree , Garcia Gustavo A. , Nahon Laurent , Dupont Jennifer , Lepère Valéria , Le Barbu-Debus Katia , Zehnacker Anne
Published: October 2023

An achiral chromophore can acquire a chiral spectroscopic signature when interacting with a chiral environment. This so-called induced chirality is documented in electronic or vibrational circular dichroism, which arises from the coupling between electric and magnetic transition dipoles. Here, we demonstrate that a chiroptical response is also induced within the electric dipole approximation by observing the asymmetric scattering of a photoelectron ejected from an achiral chromophore in interaction with a chiral host. In a phenol–methyloxirane complex, removing an electron from an achiral aromatic π orbital localised on the phenol moiety results in an intense and opposite photoelectron circular dichroism (PECD) for the two enantiomeric complexes with (R) and (S) methyloxirane, evidencing the long-range effect (~5 Å) of the scattering chiral potential. This induced chirality has important structural and analytical implications, discussed here in the context of growing interest in laser-based PECD, for in situ, real time enantiomer determination.
Concretized structural evolution supported assembly-controlled film-forming kinetics in slot-die coated organic photovoltaics
Authors: Zhang Hao , Tian Chenyang , Zhang Ziqi , Xie Meiling , Zhang Jianqi , Zhu Lingyun , Wei Zhixiang
Published: October 2023

Bulk-heterojunction structured small-area organic solar cells are approaching 20% power conversion efficiency, but the blurred film-forming kinetics in the fabrication of large-area devices causes significant PCE loss and restrains the potential of commercialization. Such blurring came from insufficient knowledge of structural evolution during the film-forming process. Here, we concretize the evolution process with structures detailed to the submolecular level by comprehensive investigations of in-situ UV-vis spectroscopy, Atomic Force Microscope, Grazing Incident Wide Angle X-ray Scattering, and molecular dynamic simulation. With such hierarchical structural knowledge, assembly-controlled film-forming kinetics is proposed to explain the whole picture. Such assembly is determined by molecule configuration and can be tuned via external conditions. Understanding this kinetics will contribute to screening large-area device fabrication conditions, and the detailed structural knowledge could inspire the future design of novel photovoltaic materials that are intrinsically excellent in large-area device fabrications.
In vivo noninvasive systemic myography of acute systemic vasoactivity in female pregnant mice
Authors: Huda Kristie , Lawrence Dylan J. , Thompson Weylan , Lindsey Sarah H. , Bayer Carolyn L.
Published: October 2023

Altered vasoactivity is a major characteristic of cardiovascular and oncological diseases, and many therapies are therefore targeted to the vasculature. Therapeutics which are selective for the diseased vasculature are ideal, but whole-body selectivity of a therapeutic is challenging to assess in practice. Vessel myography is used to determine the functional mechanisms and evaluate pharmacological responses of vascularly-targeted therapeutics. However, myography can only be performed on ex vivo sections of individual arteries. We have developed methods for implementation of spherical-view photoacoustic tomography for non-invasive and in vivo myography. Using photoacoustic tomography, we demonstrate the measurement of acute vascular reactivity in the systemic vasculature and the placenta of female pregnant mice in response to two vasodilators. Photoacoustic tomography simultaneously captures the significant acute vasodilation of major arteries and detects selective vasoactivity of the maternal-fetal vasculature. Photoacoustic tomography has the potential to provide invaluable preclinical information on vascular response that cannot be obtained by other established methods.
Asymmetric formal sp2-hydrocarbonations of dienes and alkynes via palladium hydride catalysis
Authors: Tang Ming-Qiao , Yang Zi-Jiang , He Zhi-Tao
Published: October 2023

Transition metal-catalyzed asymmetric hydrofunctionalizations of unsaturated bonds via π-ƞ3 substitution have emerged as a reliable method to construct stereogenic centers, and mainly rely on the use of heteroatom-based or carbon nucleophiles bearing acidic C-H bonds. In comparison, sp2 carbon nucleophiles are generally not under consideration because of enormous challenges in cleaving corresponding inert sp2 C-H bonds. Here, we report a protocol to achieve asymmetric formal sp2 hydrocarbonations, including hydroalkenylation, hydroallenylation and hydroketenimination of both 1,3-dienes and alkynes via hydroalkylation and Wittig reaction cascade. A series of unachievable motifs via hydrofunctionalizations, such as di-, tri- and tetra-substituted alkenes, di-, tri- and tetra-substituted allenes, and tri-substituted ketenimines in allyl skeletons are all facilely constructed in high regio-, diastereo- and enantioselectivities with this cascade design. Stereodivergent synthesis of all four stereoisomers of 1,4-diene bearing a stereocenter and Z/E-controllable olefin unit highlights the power of present protocol. An interesting mechanistic feature is revealed that alkyne actually undergoes hydrocarbonation via the formation of conjugated diene intermediate, different from conventional viewpoint that the hydrofunctionalization of alkynes only involves allene species.
Lyophilization process optimization and molecular dynamics simulation of mRNA-LNPs for SARS-CoV-2 vaccine
Authors: Li Mingyuan , Jia Lin , Xie Yanbo , Ma Wenlin , Yan Zhihong , Liu Fufeng , Deng Jie , Zhu Ali , Siwei Xue , Su Wen , Liu Xiaofeng , Li Shiqin , Wang Haomeng , Yu Peng , Zhu Tao
Published: October 2023

Some studies have shown that lyophilization significantly improves the stability of mRNA-LNPs and enables long-term storage at 2–8 °C. However, there is little research on the lyophilization process of mRNA-lipid nanoparticles (LNPs). Most previous studies have used empirical lyophilization with only a single lyoprotectant, resulting in low lyophilization efficiency, often requiring 40–100 h. In the present study, an efficient lyophilization method suitable for mRNA-LNPs was designed and optimized, shortening the total length of the lyophilization process to 8–18 h, which significantly reduced energy consumption and production costs. When the mixed lyoprotectant composed of sucrose, trehalose, and mannitol was added to mRNA-LNPs, the eutectic point and collapse temperature of the system were increased. The lyophilized product had a ginger root-shaped rigid structure with large porosity, which tolerated rapid temperature increases and efficiently removed water. In addition, the lyophilized mRNA-LNPs rapidly rehydrated and had good particle size distribution, encapsulation rate, and mRNA integrity. The lyophilized mRNA-LNPs were stable at 2–8 °C, and they did not reduce immunogenicity in vivo or in vitro. Molecular dynamics simulation was used to compare the phospholipid molecular layer with the lyoprotectant in aqueous and anhydrous environments to elucidate the mechanism of lyophilization to improve the stability of mRNA-LNPs. This efficient lyophilization platform significantly improves the accessibility of mRNA-LNPs.
Rapid discovery of high-affinity antibodies via massively parallel sequencing, ribosome display and affinity screening
Authors: Porebski Benjamin T. , Balmforth Matthew , Browne Gareth , Riley Aidan , Jamali Kiarash , Fürst Maximillian J. L. J. , Velic Mirko , Buchanan Andrew , Minter Ralph , Vaughan Tristan , Holliger Philipp
Published: October 2023

Developing therapeutic antibodies is laborious and costly. Here we report a method for antibody discovery that leverages the Illumina HiSeq platform to, within 3 days, screen in the order of 108 antibody–antigen interactions. The method, which we named ‘deep screening’, involves the clustering and sequencing of antibody libraries, the conversion of the DNA clusters into complementary RNA clusters covalently linked to the instrument’s flow-cell surface on the same location, the in situ translation of the clusters into antibodies tethered via ribosome display, and their screening via fluorescently labelled antigens. By using deep screening, we discovered low-nanomolar nanobodies to a model antigen using 4 × 106 unique variants from yeast-display-enriched libraries, and high-picomolar single-chain antibody fragment leads for human interleukin-7 directly from unselected synthetic repertoires. We also leveraged deep screening of a library of 2.4 × 105 sequences of the third complementarity-determining region of the heavy chain of an anti-human epidermal growth factor receptor 2 (HER2) antibody as input for a large language model that generated new single-chain antibody fragment sequences with higher affinity for HER2 than those in the original library.
Histones with an unconventional DNA-binding mode in vitro are major chromatin constituents in the bacterium Bdellovibrio bacteriovorus
Authors: Hocher Antoine , Laursen Shawn P. , Radford Paul , Tyson Jess , Lambert Carey , Stevens Kathryn M. , Montoya Alex , Shliaha Pavel V. , Picardeau Mathieu , Sockett R. Elizabeth , Luger Karolin , Warnecke Tobias
Published: October 2023

Histone proteins bind DNA and organize the genomes of eukaryotes and most archaea, whereas bacteria rely on different nucleoid-associated proteins. Homology searches have detected putative histone-fold domains in a few bacteria, but whether these function like archaeal/eukaryotic histones is unknown. Here we report that histones are major chromatin components in the bacteria Bdellovibrio bacteriovorus and Leptospira interrogans. Patterns of sequence evolution suggest important roles for histones in additional bacterial clades. Crystal structures (<2.0 Å) of the B. bacteriovorus histone (Bd0055) dimer and the histone–DNA complex confirm conserved histone-fold topology but indicate a distinct DNA-binding mode. Unlike known histones in eukaryotes, archaea and viruses, Bd0055 binds DNA end-on, forming a sheath of dimers encasing straight DNA rather than wrapping DNA around their outer surface. Our results demonstrate that histones are present across the tree of life and highlight potential evolutionary innovation in how they associate with DNA.
Characterization of microbial communities in seven wetlands with different anthropogenic burden using Next Generation Sequencing in Bogotá, Colombia
Authors: Ballesteros Nathalia , Páez Luisa , Luna Nicolas , Reina Ariana , Urrea Vanessa , Sánchez Catalina , Ramírez Angie , Ramirez Juan David , Muñoz Marina
Published: October 2023

Wetlands represent key ecosystems due to their remarkable biodiversity, ecological functions and multiple ecosystem services provided. In Colombia, there are 31,702 wetlands, 13 of which are in Bogotá, capital of the country. Despite the fundamental socioecological support of these aquatic ecosystems, a tremendous loss and degradation of these ecosystems has been observed due to anthropogenic perturbations. Therefore, the aim of this study was to describe the status of seven Bogotá wetlands with variable anthropogenic interventions by measuring organoleptic, physicochemical, and microbiological parameters, using commercial kits, highly sensitive equipment, and next-generation sequencing of the 16S- and 18S-rRNA genes. Our findings describe the status of seven wetlands with different anthropogenic burden in Bogotá-Colombia where physicochemical and microbiology signals of contamination were observed. Additionally, some profiles in the composition of the microbial communities, together with certain physicochemical characteristics, may represent an insight into the environmental dynamics, where Beta Proteobacteria such as Malikia represent a potential keystone in aquatic ecosystems impacted by wastewater effluent discharges; the presence of nitrates and phosphates explain the abundance of bacteria capable of oxidizing these compounds, such as Polynucleobacter. Moreover, the presence of specific prokaryotic and eukaryotic organisms, such as Clostridium, Cryptococcus, Candida, and Naegleria, reported in one or more of the wetlands assessed here, could represent a possible pathogenic risk for human and animal health. This study performed a complete evaluation of seven Bogotá wetlands with different anthropogenic impacts for the first time, and our findings emphasize the importance of maintaining continuous monitoring of these water bodies given their remarkable ecological importance and potential spill-over of several pathogens to humans and animals.
An eye tracking investigation of attention mechanism in driving behavior under emotional issues and cognitive load
Authors: Wang Quan , Zhu Feiyu , Dang Ruochen , Wei Xiaojie , Han Gongen , Huang Jinhua , Hu Bingliang
Published: October 2023

Emotions have specific effects on behavior. At present, studies are increasingly interested in how emotions affect driving behavior. We designed the experiment by combing driving tasks and eye tracking. DSM-V assessment scale was applied to evaluate the depression and manic for participants. In order to explore the dual impacts of emotional issues and cognitive load on attention mechanism, we defined the safety-related region as the area of interest (AOI) and quantified the concentration of eye tracking data. Participants with depression issues had lower AOI sample percentage and shorter AOI fixation duration under no external cognitive load. During our experiment, the depression group had the lowest accuracy in arithmetic quiz. Additionally, we used full connected network to detect the depression group from the control group, reached 83.33%. Our experiment supported that depression have negative influences on driving behavior. Participants with depression issues reduced attention to the safety-related region under no external cognitive load, they were more prone to have difficulties in multitasking when faced with high cognitive load. Besides, participants tended to reallocate more attention resources to the central area under high cognitive load, a phenomenon we called "visual centralization" in driving behavior.
Longitudinal change of gut microbiota in hypertensive disorders in pregnancy: a nested case–control and Mendelian randomization study
Authors: Wu Xinrui , Li Qi , Cai Jiawang , Huang Houxiang , Ma Shujuan , Tan Hongzhuan
Published: October 2023

Mounting evidence has shown that gut microbiota (GM) is related to hypertensive disorders in pregnancy (HDP), however, most studies only focused on one time point in pregnancy. In this study, we conducted a nested case–control study utilizing a follow-up cohort, resulting in the collection of 47 HDP patients and 30 healthy controls. The GM profiles were explored using 16S rRNA sequencing at three time points during pregnancy. The diversity analysis of GM showed no significant difference between HDP patients and controls, however, we found 21 differential GM during pregnancy. Trend analysis showed that there are statistical differences in the relative abundance of Thermomonas, Xanthomonas, and Phenylobacteriumat during pregnancy in the gestational hypertension group, and of Xanthomonas, Polycyclovorans, and Phenylobacterium in the control group. The correlation study found that six genera of GM are related to blood pressure. Furthermore, the MR analysis identified the causal relationship between Methanobrevibacter and pre-eclampsia (PE). This study first explored the longitudinal change of GM in HDP patients during pregnancy, found the differential GM, and detected the causal association. Our findings may promote the prevention and treatment of HDP from the perspective of GM and provide valuable insights into the pathogenesis of HDP.
The role of bodily self-consciousness in episodic memory of naturalistic events: an immersive virtual reality study
Authors: Penaud Sylvain , Yeh Delphine , Gaston-Bellegarde Alexandre , Piolino Pascale
Published: October 2023

Recent studies suggest that the human body plays a critical role in episodic memory. Still, the precise relationship between bodily self-consciousness (BSC) and memory formation of specific events, especially in real-life contexts, remains a topic of ongoing research. The present study investigated the relationship between BSC and episodic memory (EM) using immersive virtual reality (VR) technology. Participants were immersed in an urban environment with naturalistic events, while their visuomotor feedback was manipulated in three within-subjects conditions: Synchronous, Asynchronous, and No-body. Our results show that asynchronous visuomotor feedback and not seeing one’s body, compared to synchronous feedback, decrease the sense of self-identification, self-location and agency, and sense of presence. Moreover, navigating in the Asynchronous condition had a detrimental impact on incidental event memory, perceptual details, contextual association, subjective sense of remembering, and memory consolidation. In contrast, participants in the No-Body condition were only impaired in egocentric spatial memory and the sense of remembering at ten-day delay. We discuss these findings in relation to the role of bodily self-representation in space during event memory encoding. This study sheds light on the complex interplay between BSC, sense of presence, and episodic memory processes, and strengthens the potential of embodiment and VR technology in studying and enhancing human cognition.
Cerebrospinal fluid solute transport associated with sensorimotor brain activity in rodents
Authors: Kim Evgenii , Van Reet Jared , Yoo Seung-Schik
Published: October 2023

Cerebrospinal fluid (CSF) is crucial for maintaining neuronal homeostasis, providing nutrition, and removing metabolic waste from the brain. However, the relationship between neuronal activity and CSF solute transport remains poorly understood. To investigate the effect of regional neuronal activity on CSF solute transport, Sprague–Dawley rats (all male, n = 30) under anesthesia received an intracisternal injection of a fluorescent tracer (Texas Red ovalbumin) and were subjected to unilateral electrical stimulation of a forelimb. Two groups (n = 10 each) underwent two different types of stimulation protocols for 90 min, one including intermittent 7.5-s resting periods and the other without rest. The control group was not stimulated. Compared to the control, the stimulation without resting periods led to increased transport across most of the cortical areas, including the ventricles. The group that received intermittent stimulation showed an elevated level of solute uptake in limited areas, i.e., near/within the ventricles and on the ventral brain surface. Interhemispheric differences in CSF solute transport were also found in the cortical regions that overlap with the forelimb sensorimotor area. These findings suggest that neuronal activity may trigger local and brain-wide increases in CSF solute transport, contributing to waste clearance.
On t-intuitionistic fuzzy graphs: a comprehensive analysis and application in poverty reduction
Authors: Razzaque Asima , Masmali Ibtisam , Latif Laila , Shuaib Umer , Razaq Abdul , Alhamzi Ghaliah , Noor Saima
Published: October 2023

This paper explains the idea of t-intuitionistic fuzzy graphs as a powerful way to analyze and display relationships that are difficult to understand. The article also illustrates the ability of t-intuitionistic fuzzy graphs to establish complex relationships with multiple factors or dimensions of a physical situation under consideration. Moreover, the fundamental set operations of t-intuitionistic fuzzy graphs are proposed. The notions of homomorphism and isomorphism of t-intuitionistic fuzzy graphs are also introduced. Furthermore, the paper highlights a practical application of the proposed technique in the context of poverty reduction within a specific society. By employing t-intuitionistic fuzzy graphs, the research demonstrates the potential to address the multifaceted nature of poverty, considering various contributing factors and their interdependencies. This application showcases the versatility and effectiveness of t-intuitionistic fuzzy graphs as a tool for decision-making and policy planning in complex societal issues.
Weight-cycling over 6 years is associated with pain, physical function and depression in the Osteoarthritis Initiative cohort
Authors: Vincent Heather K. , Johnson Alisa J. , Sibille Kim T. , Vincent Kevin R. , Cruz-Almeida Yenisel
Published: October 2023

Body weight significantly impacts health and quality of life, and is a leading risk factor for the development of knee osteoarthritis (OA). Weight cycling may have more negative health consequences compared to steady high or low weight. Using the Osteoarthritis Initiative dataset, we investigated the effects of weight cycling on physical function, quality of life, and depression over 72-months compared to stable or unidirectional body weight trajectories. Participants (n = 731) had knee OA and were classified as: (1) stable-low (BMI < 25), (2) stable-overweight (BMI = 25–29.9), and (3) stable-obese (BMI ≥ 30); (4) steady-weight-loss; (5) steady-weight-gain (weight loss/gain ≥ 2.2 kg every 2-years); (6) gain–loss–gain weight cycling, and (7) loss–gain–loss weight cycling (weight loss/gain with return to baseline), based on bi-annual assessments. We compared Knee Injury and Osteoarthritis Outcome Knee-Related Quality of Life, Function in Sports and Recreation, Physical Activity in the Elderly, Short Form SF-12, repeated chair rise, 20-m gait speed, and Center for Epidemiological Studies Depression using repeated-measures ANOVA. The steady weight loss group demonstrated the worst pain, physical function, and depressive symptoms over time (p’s < 0.05). More research is needed to confirm these findings, and elucidate the mechanisms by which steady weight loss is associated with functional decline in knee OA.
Sensitivity to the sonority sequencing principle in rats (Rattus norvegicus)
Authors: Santolin Chiara , Crespo-Bojorque Paola , Sebastian-Galles Nuria , Toro Juan Manuel
Published: October 2023

Albeit diverse, human languages exhibit universal structures. A salient example is the syllable, an important structure of language acquisition. The structure of syllables is determined by the Sonority Sequencing Principle (SSP), a linguistic constraint according to which phoneme intensity must increase at onset, reaching a peak at nucleus (vowel), and decline at offset. Such structure generates an intensity pattern with an arch shape. In humans, sensitivity to restrictions imposed by the SSP on syllables appears at birth, raising questions about its emergence. We investigated the biological mechanisms at the foundations of the SSP, testing a nonhuman, non-vocal-learner species with the same language materials used with humans. Rats discriminated well-structured syllables (e.g., pras) from ill-structured ones (e.g., lbug) after being familiarized with syllabic structures conforming to the SSP. In contrast, we did not observe evidence that rats familiarized with syllables that violate such constraint discriminated at test. This research provides the first evidence of sensitivity to the SSP in a nonhuman species, which likely stems from evolutionary-ancient cross-species biological predispositions for natural acoustic patterns. Humans’ early sensitivity to the SSP possibly emerges from general auditory processing that favors sounds depicting an arch-shaped envelope, common amongst animal vocalizations. Ancient sensory mechanisms, responsible for processing vocalizations in the wild, would constitute an entry-gate for human language acquisition.
Effect of electrode materials on resistive switching behaviour of NbOx-based memristive devices
Authors: Leonetti Giuseppe , Fretto Matteo , Pirri Fabrizio Candido , De Leo Natascia , Valov Ilia , Milano Gianluca
Published: October 2023

Memristive devices that rely on redox-based resistive switching mechanism have attracted great attention for the development of next-generation memory and computing architectures. However, a detailed understanding of the relationship between involved materials, interfaces, and device functionalities still represents a challenge. In this work, we analyse the effect of electrode metals on resistive switching functionalities of NbOx-based memristive cells. For this purpose, the effect of Au, Pt, Ir, TiN, and Nb top electrodes was investigated in devices based on amorphous NbOxgrown by anodic oxidation on a Nb substrate exploited also as counter electrode. It is shown that the choice of the metal electrode regulates electronic transport properties of metal–insulator interfaces, strongly influences the electroforming process, and the following resistive switching characteristics. Results show that the electronic blocking character of Schottky interfaces provided by Au and Pt metal electrodes results in better resistive switching performances. It is shown that Pt represents the best choice for the realization of memristive cells when the NbOxthickness is reduced, making possible the realization of memristive cells characterised by low variability in operating voltages, resistance states and with low device-to-device variability. These results can provide new insights towards a rational design of redox-based memristive cells.
Machine learning-based predictive modelling for the enhancement of wine quality
Authors: Jain Khushboo , Kaushik Keshav , Gupta Sachin Kumar , Mahajan Shubham , Kadry Seifedine
Published: October 2023

The certification of wine quality is essential to the wine industry. The main goal of this work is to develop a machine learning model to forecast wine quality using the dataset. We utilised samples from the red wine dataset (RWD) with eleven distinct physiochemical properties. With the initial RWD, five machine learning (ML) models were trained and put to the test. The most accurate algorithms are Random Forest (RF) and Extreme Gradient Boosting (XGBoost). Using these two ML approaches, the top three features from a total of eleven features are chosen, and ML analysis is performed on the remaining features. Several graphs are employed to demonstrate the feature importance based on the XGBoost model and RF. Wine quality was predicted using relevant characteristics, often referred to as fundamental elements, that were shown to be essential during the feature selection procedure. When trained and tested without feature selection, with feature selection (RF), and with key attributes, the XGBoost classifier displayed 100% accuracy. In the presence of essential variables, the RF classifier performed better. Finally, to assess the precision of their predictions, the authors trained an RF classifier, validated it, and changed its hyperparameters. To address collinearity and decrease the quantity of predictors without sacrificing model accuracy, we have also used cluster analysis.
The better to eat you with: morphological disparity and enamel ultrastructure in odontocetes
Authors: Viglino Mariana , Ezcurra Martín D. , Fordyce R. Ewan , Loch Carolina
Published: October 2023

Variations in the shape and size of teeth have been associated with changes in enamel ultrastructure across odontocetes. Characterizing these features in extinct taxa can elucidate their functional morphology and feeding strategy, while also shedding light into macroevolutionary patterns during the evolutionary history of cetaceans. This study aimed to (1) describe the enamel and dentine ultrastructure of the Early Miocene odontocetesNotocetus vanbenedeniandPhoberodon arctirostrisfrom Patagonia (Argentina) and (2) quantify tooth and enamel ultrastructure morphological disparity among odontocetes. Enamel was predominantly prismatic, thin in the anterior tooth ofN. vanbenedeniandP. arctirostris; whilst thick on the posterior tooth ofN. vanbenedeni. Together with skull morphology, data suggests a raptorial feeding strategy forP. arctirostrisand a combination suction feeding method forN. vanbenedeni. Statistical analyses supported these inferences, indicating that enamel characters are useful for paleoecological research. Morphological disparity analyses showed that extant odontocetes occupy a larger morphospace and have more disparate morphologies, whilst extinct odontocetes were more similar among each other than with the extant group. There was no clear phylogenetic-based grouping, suggesting that tooth and enamel ultrastructure disparity were mainly driven by ecological pressures. These results highlight enamel ultrastructure as a source for broader-scale paleoecological studies in cetaceans.
The amniotic fluid proteome changes across gestation in humans and rhesus macaques
Authors: Shorey-Kendrick Lyndsey E. , Crosland B. Adam , Spindel Eliot R. , McEvoy Cindy T. , Wilmarth Phillip A. , Reddy Ashok P. , Zientek Keith D. , Roberts Victoria H. J. , D’Mello Rahul J. , Ryan Kimberly S. , Olyaei Amy F. , Hagen Olivia L. , Drake Matthew G. , McCarty Owen J.T. , Scottoline Brian P. , Lo Jamie O.
Published: October 2023

Amniotic fluid is a complex biological medium that offers protection to the fetus and plays a key role in normal fetal nutrition, organogenesis, and potentially fetal programming. Amniotic fluid is also critically involved in longitudinally shaping the in utero milieu during pregnancy. Yet, the molecular mechanism(s) of action by which amniotic fluid regulates fetal development is ill-defined partly due to an incomplete understanding of the evolving composition of the amniotic fluid proteome. Prior research consisting of cross-sectional studies suggests that the amniotic fluid proteome changes as pregnancy advances, yet longitudinal alterations have not been confirmed because repeated sampling is prohibitive in humans. We therefore performed serial amniocenteses at early, mid, and late gestational time-points within the same pregnancies in a rhesus macaque model. Longitudinally-collected rhesus amniotic fluid samples were paired with gestational-age matched cross-sectional human samples. Utilizing LC–MS/MS isobaric labeling quantitative proteomics, we demonstrate considerable cross-species similarity between the amniotic fluid proteomes and large scale gestational-age associated changes in protein content throughout pregnancy. This is the first study to compare human and rhesus amniotic fluid proteomic profiles across gestation and establishes a reference amniotic fluid proteome. The non-human primate model holds promise as a translational platform for amniotic fluid studies.
Flow–solid coupling analysis of underground reinforced concrete forked pipe enclosing rock and structure
Authors: Xiao Ming , Yuan Qingteng , Zhao Binxin , Deng Liang
Published: October 2023

The stability of the surrounding rock for the construction excavation and the reinforcement of the lining structure during operation in the water-rich area is a difficult problem for the design of high-head underground turnout pipes. Firstly, according to the mechanism of excavation load release and surrounding rock damage evolution, the seepage effect of excavation in the construction of the forked caves is coupled to the surrounding rock stress damage, and an iterative method of numerical simulation of the coupled mutual feedback effect of excavation surrounding rock stress and seepage is proposed. Then, based on the cracking characteristics of the high internal water pressure reinforced concrete turnpike lining, a numerical analysis method of the coupling interaction between lining cracking and internal water seepage is proposed by coupling internal water seepage to stress damage in the lining by cracking the forked pipe structure. Applying the aforementioned method to a forked pipe project, the results show that: during the construction period, there is a significant increase in the damage zone, stress, and displacement of the rock around the cavern after considering the coupled iterations; during the operation period, with the increase in internal water pressure, the lining structure accelerates cracking due to the external infiltration of internal water; after the internal water is applied, the surrounding rock bears the main internal water pressure and the reinforcement bears only part of the circumferential force. The method provides theoretical support for the analysis and calculation of the reinforcement of similar underground high-pressure tunnels for rock support and lining structures and has certain theoretical and engineering significance.
A model of hepatic steatosis with declined viability and function in a liver-organ-on-a-chip
Authors: Wiriyakulsit Natsupa , Keawsomnuk Ploychanok , Thongin Saowarose , Ketsawatsomkron Pimonrat , Muta Kenjiro
Published: October 2023

Nonalcoholic fatty liver disease (NAFLD) begins with benign steatosis caused by ectopic storage of triacylglycerols in the liver. Persistent steatosis, in combination with other genetic and environmental factors, leads to nonalcoholic steatohepatitis (NASH) characterized by functional impairment, inflammation, and fibrosis. However, it remains unclear how persistent steatosis directly contributes to the progression of NAFLD, which may represent a therapeutic target. The organ-on-a-chip (OOC) has emerged as a new culture platform to recapitulate human pathological conditions under which drug candidates can be screened. Here, we developed a simple OOC steatosis model using the Mimetas OrganoPlate with a human liver cell line, HepG2. Treating the HepG2 OOCs with fatty acid overload induced steatosis within 24 h. Moreover, persistent steatosis for 6 days impaired OOC viability and hepatic function, as measured by a WST-8 assay and albumin production, respectively. Lastly, the HepG2 OOCs were exposed to drugs being tested in clinical trials for NAFLD/NASH during the 6-day period. Pioglitazone improved the OOC viability while elafibranor reduced the steatosis in association with reduced viability and albumin production. In conclusion, we show that the HepG2 steatosis OOC model is a useful tool on which the efficacy and toxicity of various therapeutic candidates can be tested.
Use of natural biotechnological processes to modify the nutritional properties of bean-based and lentil-based beverages
Authors: Cichońska Patrycja , Bryś Joanna , Ziarno Małgorzata
Published: October 2023

The market for plant-based beverages (PBBs) is relatively new; hence, to enable its further development, it is important to use new raw materials and improve production technology. The use of natural biotechnological processes can diversify the segment of PBBs, which may offer products with better functionality than those available in the market. Therefore, the present study aimed to determine the effects of fermentation and germination on the nutritional properties of bean-based beverages (BBs) and lentil-based beverages (LBs). The applied processes significantly (p ≤ 0.05) influenced the characteristics of PBBs. Fermentation improved the antioxidant properties (e.g., by increasing the level of 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity by 2–6% and 3–7% for BBs and LBs, respectively) and modified the fatty acid (FA) profile of PBBs. This process increased the share of polyunsaturated FAs in the sn2 position in triacylglycerols, which may promote its absorption in the intestine. The simultaneous use of germination and fermentation was most effective in decreasing oligosaccharide content (< 1.55 mg/kg), which may reduce digestive discomfort after consuming PBBs. We recommend that the designing of innovative legume-based beverages should include the application of fermentation and germination to obtain products with probiotic bacteria and improved nutritional properties.
The association of intracranial atherosclerosis with cerebral small vessel disease imaging markers: a high-resolution magnetic resonance imaging study
Authors: Zhu Kang-Li , Shang Zi-Yang , Liu Bai-jun , Wang Ying , Li Jing , Yang Ben-Qiang , Ntaios George , Chen Hui-Sheng
Published: October 2023

To evaluate the association of intracranial non-stenotic atherosclerotic plaque with cerebral small vessel disease (CSVD) imaging markers in a CSVD population using 3.0 T high-resolution magnetic resonance imaging (HRMRI), which was validated in embolic stroke of undetermined source (ESUS) cohort. We retrospectively recruited consecutive patients who were diagnosed with CSVD or ESUS from January 2015 to December 2019. All patients underwent intracranial HRMRI to assess intracranial non-stenotic atherosclerotic plaques. Baseline and imaging data were collected and were measured among all patients. Among 153 patients with CSVD, there were 59 with intracranial atherosclerotic plaque (IAP) and 94 with non-IAP, including 36 with intracranial atherosclerotic complicated plaque (IACP). Among 227 ESUS patients, there were 155 with IAP and 72 with non-IAP, including 127 with IACP. In the CSVD population, we found that: (1) CSVD burden was associated with IAP (p = 0.036) and IACP (p = 0.008); (2) IAP was associated with white matter hyperintensity (51% vs. 34%; P = 0.039), and IACP was associated with lacunes (69% vs. 35%; P = 0.009) and enlarge perivascular space (69% vs. 39%; P = 0.022). A similar association of CSVD imaging markers with IAP or IACP was found in the ESUS population. Furthermore, the association of unilateral IAP or IACP with CSVD imaging markers of ipsilateral hemisphere was identified in the two cohorts. This is the first report that intracranial non-stenotic atherosclerotic plaque, especially complicated plaque, is closely associated with CSVD imaging markers, which provide further evidence for the association of large artery atherosclerosis with CSVD.
Novel GPR156 variants confirm its role in moderate sensorineural hearing loss
Authors: Ramzan Memoona , Bozan Nazim , Seyhan Serhat , Zafeer Mohammad Faraz , Ayral Aburrahman , Duman Duygu , Bademci Guney , Tekin Mustafa
Published: October 2023

Hereditary hearing loss (HL) is a genetically heterogeneous disorder affecting people worldwide. The implementation of advanced sequencing technologies has significantly contributed to the identification of novel genes involved in HL. In this study, probands of two Turkish families with non-syndromic moderate HL were subjected to exome sequencing. The data analysis identified the c.600G > A (p.Thr200Thr) and c.1863dupG (p.His622fs) variants in GPR156, which co-segregated with the phenotype as an autosomal recessive trait in the respective families. The in silico predictions and a minigene assay showed that the c.600G > A variant disrupts mRNA splicing. This gene belongs to the family of G protein-coupled receptors whose function is not well established in the inner ear. GPR156 variants have very recently been reported to cause HL in three families. Our study from a different ethnic background confirms GPR156 as a bona fide gene involved in HL in humans. Further investigation towards the understanding of the role of GPCRs in the inner ear is warranted.
Snoring might be a warning sign for metabolic syndrome in nonobese Korean women
Authors: Chang Suk Won , Lee Ha Young , Choi Hyun Seung , Chang Jung Hyun , Lim Gil Chai , Kang Ju Wan
Published: October 2023

Metabolic syndrome (MetS) is an underlying cause of various diseases and is strongly associated with mortality. In particular, it has been steadily increasing along with changes in diet and lifestyle habits. The close relationship between sleep apnea and MetS is well established. In addition, these two diseases share a common factor of obesity and have a high prevalence among obese individuals. Nevertheless, the association can vary depending on factors, such as race and sex, and research on the relatively low obesity rates among East Asians is lacking. This study aimed to investigate the association between snoring and MetS in nonobese Koreans. A total of 2478 participants (827 men and 1651 women) were enrolled in the Korean National Health and Nutrition Examination Survey from 2019 to 2020. We used the National Cholesterol Education Program Adult Treatment Panel III criteria for MetS and a snoring questionnaire. Logistic regression analysis was used to measure the association between MetS and various confounding factors according to age and sex in participants with body mass index (BMI) < 23 kg/m2. MetS was significantly higher in participants with snoring than in those without snoring (26.9% vs. 19.6%; p = 0.007). In multivariate logistic regression analysis, age (odds ratio [OR] 1.070, 95% confidence interval [CI] 1.059–1.082, p < .001), sex (OR 1.531, 95% CI 1.139–2.058, p = 0.005), and snoring (OR 1.442, 95% CI 1.050–1.979, p = 0.024) were significantly associated with MetS in patients with a BMI < 23 kg/m2. Finally, regression analysis showed that snoring was significantly associated with MetS in women with a BMI of less than 23 kg/m2, especially with younger ages (40–49 years, OR 4.449, 95% CI 1.088 to 18.197, p = 0.038). Snoring was closely associated with MetS in women aged 40–50 years with a BMI of less than 23 kg/m2 compared to other participants. However, the association was not found in women aged 60 and over. Therefore, sufficient consideration should be given to the possibility of MetS when snoring is present in nonobese middle-aged Asian women.
Advantages and developments of Raman spectroscopy for electroceramics
Authors: Deluca Marco , Hu Hailong , Popov Maxim N. , Spitaler Jürgen , Dieing Thomas
Published: October 2023

Despite being applied with success in many fields of materials science, Raman spectroscopy is not yet determinant in the study of electroceramics. Recent experimental and theoretical developments, however, should increase the popularity of Raman spectroscopy in this class of materials. In this review, we outline the fields of application of Raman spectroscopy and microscopy in various electroceramic systems, defining current key bottlenecks and explaining promising recent developments. We focus our attention on recent experimental developments, including coupling Raman spectroscopy with other methodologies and modelling approaches involving both the model-based data interpretation and the ab initio calculation of realistic Raman spectra.
A multibody kinematic system approach for the design of shape-morphing mechanism-based metamaterials
Authors: de Jong Pier H. , Schwab A. L. , Mirzaali Mohammad J. , Zadpoor Amir A.
Published: October 2023

Shape-morphing structures have the ability to adapt to various target shapes, offering significant advantages for many applications. However, predicting their behavior presents challenges. Here, we present a method to assess the shape-matching behavior of shape-morphing structures using a multibody systems approach wherein the structure is represented by a collection of nodes and their associated constraints. This representation preserves the kinematic properties of the original structure while allowing for a rigorous treatment of the shape-morphing behavior of the underlying metamaterial. We assessed the utility of the proposed method by applying it to a wide range of 2D/3D sample shape-morphing structures. A modular system of joints and links was also 3D printed for the experimental realization of the systems under study. Both our simulations and the experiments confirmed the ability of the presented technique to capture the true shape-morphing behavior of complex shape-morphing metamaterials.