bluuebunny/crossref_metadata_2025 huggingface dataset:
Enterohaemorrhagic E. coli utilizes host- and microbiota-derived L-malate as a signaling molecule for intestinal colonization
Authors: Liu Bin , Jiang Lingyan , Liu Yutao , Sun Hongmin , Yan Jun , Kang Chenbo , Yang Bin
Published: November 2023

The mammalian gastrointestinal tract is a complex environment that hosts a diverse microbial community. To establish infection, bacterial pathogens must be able to compete with the indigenous microbiota for nutrients, as well as sense the host environment and modulate the expression of genes essential for colonization and virulence. Here, we found that enterohemorrhagic Escherichia coli (EHEC) O157:H7 imports host- and microbiota-derived L-malate using the DcuABC transporters and converts these substrates into fumarate to fuel anaerobic fumarate respiration during infection, thereby promoting its colonization of the host intestine. Moreover, L-malate is important not only for nutrient metabolism but also as a signaling molecule that activates virulence gene expression in EHEC O157:H7. The complete virulence-regulating pathway was elucidated; the DcuS/DcuR two-component system senses high L-malate levels and transduces the signal to the master virulence regulator Ler, which in turn activates locus of enterocyte effacement (LEE) genes to promote EHEC O157:H7 adherence to epithelial cells of the large intestine. Disruption of this virulence-regulating pathway by deleting either dcuS or dcuR significantly reduced colonization by EHEC O157:H7 in the infant rabbit intestinal tract; therefore, targeting these genes and altering physiological aspects of the intestinal environment may offer alternatives for EHEC infection treatment.
Gut butyrate-producers confer post-infarction cardiac protection
Authors: Chen Hung-Chih , Liu Yen-Wen , Chang Kuan-Cheng , Wu Yen-Wen , Chen Yi-Ming , Chao Yu-Kai , You Min-Yi , Lundy David J. , Lin Chen-Ju , Hsieh Marvin L. , Cheng Yu-Che , Prajnamitra Ray P. , Lin Po-Ju , Ruan Shu-Chian , Chen David Hsin-Kuang , Shih Edward S. C. , Chen Ke-Wei , Chang Shih-Sheng , Chang Cindy M. C. , Puntney Riley , Moy Amy Wu , Cheng Yuan-Yuan , Chien Hsin-Yuan , Lee Jia-Jung , Wu Deng-Chyang , Hwang Ming-Jing , Coonen Jennifer , Hacker Timothy A. , Yen C-L. Eric , Rey Federico E. , Kamp Timothy J. , Hsieh Patrick C. H.
Published: November 2023

The gut microbiome and its metabolites are increasingly implicated in several cardiovascular diseases, but their role in human myocardial infarction (MI) injury responses have yet to be established. To address this, we examined stool samples from 77 ST-elevation MI (STEMI) patients using 16 S V3-V4 next-generation sequencing, metagenomics and machine learning. Our analysis identified an enriched population of butyrate-producing bacteria. These findings were then validated using a controlled ischemia/reperfusion model using eight nonhuman primates. To elucidate mechanisms, we inoculated gnotobiotic mice with these bacteria and found that they can produce beta-hydroxybutyrate, supporting cardiac function post-MI. This was further confirmed using HMGCS2-deficient mice which lack endogenous ketogenesis and have poor outcomes after MI. Inoculation increased plasma ketone levels and provided significant improvements in cardiac function post-MI. Together, this demonstrates a previously unknown role of gut butyrate-producers in the post-MI response.
Cryo-electron tomography of NLRP3-activated ASC complexes reveals organelle co-localization
Authors: Liu Yangci , Zhai Haoming , Alemayehu Helen , Boulanger Jérôme , Hopkins Lee J. , Borgeaud Alicia C. , Heroven Christina , Howe Jonathan D. , Leigh Kendra E. , Bryant Clare E. , Modis Yorgo
Published: November 2023

NLRP3 induces caspase-1-dependent pyroptotic cell death to drive inflammation. Aberrant activity of NLRP3 occurs in many human diseases. NLRP3 activation induces ASC polymerization into a single, micron-scale perinuclear punctum. Higher resolution imaging of this signaling platform is needed to understand how it induces pyroptosis. Here, we apply correlative cryo-light microscopy and cryo-electron tomography to visualize ASC/caspase-1 in NLRP3-activated cells. The puncta are composed of branched ASC filaments, with a tubular core formed by the pyrin domain. Ribosomes and Golgi-like or endosomal vesicles permeate the filament network, consistent with roles for these organelles in NLRP3 activation. Mitochondria are not associated with ASC but have outer-membrane discontinuities the same size as gasdermin D pores, consistent with our data showing gasdermin D associates with mitochondria and contributes to mitochondrial depolarization.
Development of a radical polymerization algorithm for molecular dynamics simulations of antifreezing hydrogels with double-network structures
Authors: Liu Yonglan , Zhang Dong , Tang Yijing , Gong Xiong , Zheng Jie
Published: November 2023

The development and understanding of antifreezing hydrogels are crucial both in principle and practice for the design and delivery of new materials. The current antifreezing mechanisms in hydrogels are almost exclusively derived from their incorporation of antifreezing additives, rather than from the inherent properties of the polymers themselves. Moreover, developing a computational model for the independent yet interconnected double-network (DN) structures in hydrogels has proven to be an exceptionally difficult task. Here, we develop a multiscale simulation platform, integrating ‘random walk reactive polymerization’ (RWRP) with molecular dynamics (MD) simulations, to computationally construct a physically-chemically linked PVA/PHEAA DN hydrogels from monomers that mimic a radical polymerization and to investigate water structures, dynamics, and interactions confined in PVA/PHEAA hydrogels with various water contents and temperatures, aiming to uncover antifreezing mechanism at atomic levels. Collective simulation results indicate that the antifreezing property of PVA/PHEAA hydrogels arises from a combination of intrinsic, strong water-binding networks and crosslinkers and tightly crosslinked and interpenetrating double-network structures, both of which enhance polymer-water interactions for competitively inhibiting ice nucleation and growth. These computational findings provide atomic-level insights into the interplay between polymers and water molecules in hydrogels, which may determine their resistance to freezing.
Greenland-wide accelerated retreat of peripheral glaciers in the twenty-first century
Authors: Larocca L. J. , Twining–Ward M. , Axford Y. , Schweinsberg A. D. , Larsen S. H. , Westergaard–Nielsen A. , Luetzenburg G. , Briner J. P. , Kjeldsen K. K. , Bjørk A. A.
Published: November 2023

The long-term response of Greenland’s peripheral glaciers to climate change is widely undocumented. Here we use historical aerial photographs and satellite imagery to document length fluctuations of >1,000 land-terminating peripheral glaciers in Greenland over more than a century. We find that their rate of retreat over the last two decades is double that of the twentieth century, indicating a ubiquitous transition into a new, accelerated state of downwasting.
RETRACTED ARTICLE: High replicability of newly discovered social-behavioural findings is achievable
Authors: Protzko John , Krosnick Jon , Nelson Leif , Nosek Brian A. , Axt Jordan , Berent Matt , Buttrick Nicholas , DeBell Matthew , Ebersole Charles R. , Lundmark Sebastian , MacInnis Bo , O’Donnell Michael , Perfecto Hannah , Pustejovsky James E. , Roeder Scott S. , Walleczek Jan , Schooler Jonathan W.
Published: November 2023

Failures to replicate evidence of new discoveries have forced scientists to ask whether this unreliability is due to suboptimal implementation of methods or whether presumptively optimal methods are not, in fact, optimal. This paper reports an investigation by four coordinated laboratories of the prospective replicability of 16 novel experimental findings using rigour-enhancing practices: confirmatory tests, large sample sizes, preregistration and methodological transparency. In contrast to past systematic replication efforts that reported replication rates averaging 50%, replication attempts here produced the expected effects with significance testing (P < 0.05) in 86% of attempts, slightly exceeding the maximum expected replicability based on observed effect sizes and sample sizes. When one lab attempted to replicate an effect discovered by another lab, the effect size in the replications was 97% that in the original study. This high replication rate justifies confidence in rigour-enhancing methods to increase the replicability of new discoveries.
Dynamic intravital imaging reveals reactive vessel-associated microglia play a protective role in cerebral malaria coagulopathy
Authors: Solomon Olivia D. , Villarreal Paula , Domingo Nadia D. , Ochoa Lorenzo , Vanegas Difernando , Cardona Sandra M. , Cardona Astrid E. , Stephens Robin , Vargas Gracie
Published: November 2023

Vascular congestion and coagulopathy have been shown to play a role in human and experimental cerebral malaria (eCM), but little is known about the role of microglia, or microglia-vascular interactions and hypercoagulation during disease progression in this fatal infection. Recent studies show microglia bind to fibrinogen, a glycoprotein involved in thrombosis. An eCM model of Plasmodium chabaudi infection in mice deficient in the regulatory cytokine IL-10 manifests neuropathology, including hypercoagulation with extensive fibrin(ogen) deposition and neuroinflammation. Intravital microscopy and immunofluorescence are applied to elucidate the role of microglia in eCM. Results show microgliosis and coagulopathy occur early in disease at 3 dpi (day post-infection), and both are exacerbated as disease progresses to 7dpi. Vessel associated microglia increase significantly at 7 dpi, and the expression of the microglial chemoattractant CCL5 (RANTES) is increased versus uninfected and localized with fibrin(ogen) in vessels. PLX3397 microglia depletion resulted in rapid behavioral decline, severe hypothermia, and greater increase in vascular coagulopathy. This study suggests that microglia play a prominent role in controlling infection-initiated coagulopathy and supports a model in which microglia play a protective role in cerebral malaria by migrating to and patrolling the cerebral vasculature, potentially regulating degree of coagulation during systemic inflammation.
Need for Cognition is associated with a preference for higher task load in effort discounting
Authors: Zerna Josephine , Scheffel Christoph , Kührt Corinna , Strobel Alexander
Published: November 2023

When individuals set goals, they consider the subjective value (SV) of the anticipated reward and the required effort, a trade-off that is of great interest to psychological research. One approach to quantify the SVs of levels of difficulty of a cognitive task is the Cognitive Effort Discounting Paradigm by Westbrook and colleagues (2013). However, it fails to acknowledge the highly individual nature of effort, as it assumes a unidirectional, inverse relationship between task load and SVs. Therefore, it cannot map differences in effort perception that arise from traits like Need for Cognition, since individuals who enjoy effortful cognitive activities likely do not prefer the easiest level. We replicated the analysis of Westbrook and colleagues with an adapted version, the Cognitive and Affective Discounting (CAD) Paradigm. It quantifies SVs without assuming that the easiest level is preferred, thereby enabling the assessment of SVs for tasks without objective order of task load. Results show that many of the 116 participants preferred a more or the most difficult level. Variance in SVs was best explained by a declining logistic contrast of the $$n$$
n
-back levels and by the accuracy of responses, while reaction time as a predictor was highly volatile depending on the preprocessing pipeline. Participants with higher Need for Cognition scores perceived higher $$n$$
n
-back levels as less effortful and found them less aversive. Effects of Need for Cognition on SVs in lower levels did not reach significance, as group differences only emerged in higher levels. The CAD Paradigm appears to be well suited for assessing and analysing task preferences independent of the supposed objective task difficulty.

Protocol registrationThe stage 1 protocol for this Registered Report was accepted in principle on August 19, 2022. The protocol, as accepted by the journal, can be found at: https://doi.org/10.17605/OSF.IO/CPXTH.
Contribution of sex and gender roles to the incidence of post-infectious irritable bowel syndrome in a prospective study
Authors: Park Jae Ho , Kang Sun Hyung , Kim Ju Seok , Moon Hee Seok , Sung Jae Kyu , Jeong Hyun Yong
Published: November 2023

Post-infectious irritable bowel syndrome (PI-IBS) occurs in about 10% of cases following gastroenteritis. The incidence of IBS is higher in females. However, it is not clear whether this is due to biological or psychosocial factors. We aimed to investigate the influence of gender roles on the incidence of PI-IBS, alongside traditional risk factors. Our study included 231 patients diagnosed with gastroenteritis who were hospitalized and treated with antibiotics between 2018 and 2021. The Korean Sex Role Inventory-Short Form (KSRI-SF), based on the Bem Sex Role Inventory (BSRI) was used to categorize patients (androgynous, masculine, feminine, and undifferentiated types). Six months after treatment, we conducted a telephone survey to confirm the presence of PI-IBS using the ROME IV criteria. Among the patients, 43.3% were female, and the mean age was 43.67 ± 16.09 years. After 6 months, 34 patients developed PI-IBS. Univariate analysis revealed that younger age, female sex, KSRI-SF undifferentiated type, and longer duration of antibiotic use independently influenced the occurrence of PI-IBS. Multivariate analysis showed that PI-IBS was associated with the KSRI-SF undifferentiated type and higher C-reactive protein (CRP) levels. Our study showed that the KSRI-SF undifferentiated type and high CRP levels at initial infection were associated with PI-IBS.
Expanding our view of the cold-water coral niche and accounting of the ecosystem services of the reef habitat
Authors: Cordes Erik E. , Demopoulos Amanda W. J. , Davies Andrew J. , Gasbarro Ryan , Rhoads Alexandria C. , Lobecker Elizabeth , Sowers Derek , Chaytor Jason D. , Morrison Cheryl L. , Weinnig Alexis M. , Brooke Sandra , Lunden Jay J. , Mienis Furu , Joye Samantha B. , Quattrini Andrea M. , Sutton Tracey T. , McFadden Catherine S. , Bourque Jill R. , McClain-Counts Jennifer P. , Andrews Brian D. , Betters Melissa J. , Etnoyer Peter J. , Wolff Gary A. , Bernard Bernie B. , Brooks James M. , Rasser Michael K. , Adams Caitlin
Published: November 2023

Coral reefs are iconic ecosystems that support diverse, productive communities in both shallow and deep waters. However, our incomplete knowledge of cold-water coral (CWC) niche space limits our understanding of their distribution and precludes a complete accounting of the ecosystem services they provide. Here, we present the results of recent surveys of the CWC mound province on the Blake Plateau off the U.S. east coast, an area of intense human activity including fisheries and naval operations, and potentially energy and mineral extraction. At one site, CWC mounds are arranged in lines that total over 150 km in length, making this one of the largest reef complexes discovered in the deep ocean. This site experiences rapid and extreme shifts in temperature between 4.3 and 10.7 °C, and currents approaching 1 m s−1. Carbon is transported to depth by mesopelagic micronekton and nutrient cycling on the reef results in some of the highest nitrate concentrations recorded in the region. Predictive models reveal expanded areas of highly suitable habitat that currently remain unexplored. Multidisciplinary exploration of this new site has expanded understanding of the cold-water coral niche, improved our accounting of the ecosystem services of the reef habitat, and emphasizes the importance of properly managing these systems.
Unveiling an unexpected superoxide-mediated photooxidation mechanism of squalene monohydroperoxides to squalene hydroperoxy cyclic peroxides through ESR and LC–MS/MS analyses
Authors: Khalifa Saoussane , Enomoto Masaru , Nakagawa Kiyotaka
Published: November 2023

Lipid cyclic peroxides are a rarely reported and documented class of compounds in the human organism. Recently, we reported the formation of squalene (SQ) hydroperoxy cyclic peroxides derived from SQ monohydroperoxide isomers (SQ-OOHs) for the first time. Notably, we successfully detected and quantified cis-2-OOH-3-(1,2-dioxane)-SQ in the human skin. Nevertheless, the underlying mechanism governing the formation of these compounds remained elusive. Therefore, in the current study, we set to determine the reaction’s mechanism. To this end, a comprehensive analysis of the precise conditions involved in the onset and propagation of this conversion was carried out by oxidizing total SQ-OOHs under different conditions, including singlet oxygen (1O2), thermal, and photoinduced oxidations monitored by quantifying the generated 2-OOH-3-(1,2-dioxane)-SQ using liquid chromatography-tandem mass spectrometry (LC–MS/MS). Radical intermediates were thoroughly investigated using Electron Spin Resonance (ESR) with the aid of spin traps and radical references. Moreover, calculations of SQ-OOHs’ electrostatic charges were performed on Spartan 18 software. We found that the reaction is ideally induced and favored under photooxidation in the presence of 3O2 in hexane, and that superoxide radical (O2•−) is the first key intermediate in this mechanism, whereas peroxyl radicals were the major species observed throughout the oxidation. Chemical calculations provided an explanation for the targeting of tertiary SQ-OOHs by this reaction and gave further evidence on the proposed heterolytic cleavage initiating the reaction. The novel oxidation mechanism suggested herein offers new insights into understanding lipid secondary oxidation and is a promising finding for further studying lipid cyclic peroxides in general.
Aminothiol supported dialdehyde cellulose for efficient and selective removal of Hg(II) from aquatic solutions
Authors: Mostafa Aya G. , Gaith Eslam A. , Akl Magda A.
Published: November 2023

The increasingly serious problem of mercury pollution has caused wide concern, and exploring adsorbent materials with high adsorption capacity is a simple and effective approach to address this concern. In the recent study, dialdehyde cellulose (DAC), cyanoacetohydrazide (CAH), and carbon disulfide (CS2) are used as raw materials for the (DAC@CAH@SK2) preparation material through the three-steps method. By utilizing the following characterization techniques; thermogravimetric analysis (TGA), N2 adsorption–desorption isotherm (BET), elemental analysis, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD), 1HNMR and Energy Dispersive X-ray Spectroscopy (EDS) of DAC@CAH@SK2 composite. The point of zero charge (pHPZC) for the prepared DAC@CAH@SK2 also was examined. From the batch experiments, the optimum conditions were found to be pH (5–8), an Hg2+ concentration of 150 mg/L, a DAC@CAH@SK2 dose of 0.01 g, and a contact time of 180 min with a maximum adsorption quantity of 139.6 mg/g. The process of Hg2+ adsorption on the DAC@CAH@SK2 material was spontaneous exothermic, monolayer chemisorption, and well-fitted to Langmuir and pseudo-2nd-order models. The DAC@CAH@SK2 selectivity towards the Hg2+ was examined by investigating the interfering metal ions effect. The DAC@CAH@SK2 was successfully applied for the Hg2+ removal from synthetic effluents and real wastewater samples with a recovery % exceeding 95%. The prepared DAC@CAH@SK2 was regenerated using a mixture of EDTA and thiourea. Also, FT-IR analysis indicates that the synergistic complexation of N and S atoms on DAC@CAH@SK2 with Hg(II) is an essential factor leading to the high adsorption capacity.
The Property Rights Index (PRIF) can be used worldwide to compare different forest governance systems
Authors: Rimoli Richard , Nichiforel Liviu , Acharya Aditya , Nollet Alexandre , Snoussi Bilal , Ambroise Lison , Cordonnier Louis , Mares Sandra Galván , Zúñiga José Jonathan Aguirre , Bontemps Jean-Daniel , Bouriaud Laura
Published: November 2023

The bundle of forest landowners’ rights largely varies from one jurisdiction to another. On a global scale, the diversity of forest management regime and property rights systems is such that finding comprehensive and standardised approaches for governance analysis purposes is a challenging task. This paper explores the use of the Property Rights Index for Forestry (PRIF) as an analytical tool based on five rights domains (access, withdrawal, management, exclusion, and alienation) to assess how regulatory frameworks impact the owners’ forest property rights. We show that PRIF is a reliable index for various governance arrangements, considering its ability to score forest owners’ freedom to decide in case studies that range from the Amazon area (Brazil), Misiones province (Argentina) and Quebec (Canada) to community-managed Nepalese and Mexican forests. PRIF scores obtained in these diverse governance arrangements confirm that the governance of forests held by entities other than the state is driven by two factors: the owner’s ability to exclude the public from the use of his/her own resource and the owner’s freedom to decide on the forest management goals. These factors explained 66.44% of the variance in our sample and should be considered as the main potential drivers while implementing any new international or national policy. Despite having a few limitations, the PRIF is a promising governance indicator and has been proven to perform well for various socioeconomic and legal contexts.
A micro-LED array based platform for spatio-temporal optogenetic control of various cardiac models
Authors: Junge Sebastian , Ricci Signorini Maria Elena , Al Masri Masa , Gülink Jan , Brüning Heiko , Kasperek Leon , Szepes Monika , Bakar Mine , Gruh Ina , Heisterkamp Alexander , Torres-Mapa Maria Leilani
Published: November 2023

Optogenetics relies on dynamic spatial and temporal control of light to address emerging fundamental and therapeutic questions in cardiac research. In this work, a compact micro-LED array, consisting of 16 × 16 pixels, is incorporated in a widefield fluorescence microscope for controlled light stimulation. We describe the optical design of the system that allows the micro-LED array to fully cover the field of view regardless of the imaging objective used. Various multicellular cardiac models are used in the experiments such as channelrhodopsin-2 expressing aggregates of cardiomyocytes, termed cardiac bodies, and bioartificial cardiac tissues derived from human induced pluripotent stem cells. The pacing efficiencies of the cardiac bodies and bioartificial cardiac tissues were characterized as a function of illumination time, number of switched-on pixels and frequency of stimulation. To demonstrate dynamic stimulation, steering of calcium waves in HL-1 cell monolayer expressing channelrhodopsin-2 was performed by applying different configurations of patterned light. This work shows that micro-LED arrays are powerful light sources for optogenetic control of contraction and calcium waves in cardiac monolayers, multicellular bodies as well as three-dimensional artificial cardiac tissues.
National trends in rheumatoid arthritis and osteoarthritis prevalence in South Korea, 1998–2021
Authors: Park Jaeyu , Lee Myeongcheol , Lee Hojae , Kim Hyeon Jin , Kwon Rosie , Yang Hwi , Lee Seung Won , Kim Sunyoung , Rahmati Masoud , Koyanagi Ai , Smith Lee , Kim Min Seo , Jacob Louis , López Sánchez Guillermo Felipe , Elena Dragioti , Shin Jae Il , Rhee Sang Youl , Yoo Myung Chul , Yon Dong Keon
Published: November 2023

Studies on the trends in the prevalence of rheumatoid arthritis (RA) and osteoarthritis (OA) are limited, particularly during the COVID-19 pandemic. This study aimed to analyze the temporal trend of RA and OA in South Korean adults from 1998 to 2021, including the COVID-19 pandemic period. The Korea National Health and Nutrition Examination Survey (KNHANES) data on adults aged ≥ 19 years were analyzed to investigate the prevalence of RA and OA from 1998 to 2021. The prevalence trends were compared by the years, and βdiff (β difference) was calculated. Odds ratios (ORs) were computed for each disease to examine changes in disease prevalence before and during the pandemic in order to determine the impact of the pandemic on disease prevalence. Among 163,221 Korean adults, the prevalence of RA and OA showed a steady decrease from 2005 (RA: from 1.91% in 2005–2007 to 1.55% in 2016–2019 and OA: from 9.75% in 2005–2007 to 8.27% in 2016–2019), but there was a slight increased after the onset of the COVID-19 pandemic (RA: from 1.23% in 2020 to 1.36% in 2021 and OA: from 8.04% in 2020 to 8.27% in 2021). Vulnerable groups, including participants aged ≥ 60 years (versus 19–60 years, ratio of ORs: 1.222; 95% CI 1.011–1.477), urban residents (ratio of ORs: 1.289; 95% CI 1.007–1.650), and participants with higher education level (ratio of ORs: 1.360; 95% CI 1.119–1.653) showed higher ORs of OA, whereas no particularly vulnerable population was observed for RA. Our findings provide an insight into the long-term trends of RA and OA among adult population and highlight a novel perspective on the impact of COVID-19 on disease prevalence.
Deep brain stimulation in disorders of consciousness: 10 years of a single center experience
Authors: Chudy Darko , Deletis Vedran , Paradžik Veronika , Dubroja Ivan , Marčinković Petar , Orešković Darko , Chudy Hana , Raguž Marina
Published: November 2023

Disorders of consciousness (DoC), namely unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), represent severe conditions with significant consequences for patients and their families. Several studies have reported the regaining of consciousness in such patients using deep brain stimulation (DBS) of subcortical structures or brainstem nuclei. Our study aims to present the 10 years’ experience of a single center using DBS as a therapy on a cohort of patients with DoC. Eighty Three consecutive patients were evaluated between 2011 and 2022; entry criteria consisted of neurophysiological and neurological evaluations and neuroimaging examinations. Out of 83, 36 patients were considered candidates for DBS implantation, and 32 patients were implanted: 27 patients had UWS, and five had MCS. The stimulation target was the centromedian-parafascicular complex in the left hemisphere in hypoxic brain lesion or the one better preserved in patients with traumatic brain injury. The level of consciousness was improved in seven patients. Three out of five MCS patients emerged to full awareness, with the ability to interact and communicate. Two of them can live largely independently. Four out of 27 UWS patients showed consciousness improvement with two patients emerging to full awareness, and the other two reaching MCS. In patients with DoC lasting longer than 12 months following traumatic brain injury or 6 months following anoxic-ischemic brain lesion, spontaneous recovery is rare. Thus, DBS of certain thalamic nuclei could be recommended as a treatment option for patients who meet neurological, neurophysiological and neuroimaging criteria, especially in earlier phases, before occurrence of irreversible musculoskeletal changes. Furthermore, we emphasize the importance of cooperation between centers worldwide in studies on the potentials of DBS in treating patients with DoC.
The role of long-term power-law memory in controlling large-scale dynamical networks
Authors: Reed Emily A. , Ramos Guilherme , Bogdan Paul , Pequito Sérgio
Published: November 2023

Controlling large-scale dynamical networks is crucial to understand and, ultimately, craft the evolution of complex behavior. While broadly speaking we understand how to control Markov dynamical networks, where the current state is only a function of its previous state, we lack a general understanding of how to control dynamical networks whose current state depends on states in the distant past (i.e. long-term memory). Therefore, we require a different way to analyze and control the more prevalent long-term memory dynamical networks. Herein, we propose a new approach to control dynamical networks exhibiting long-term power-law memory dependencies. Our newly proposed method enables us to find the minimum number of driven nodes (i.e. the state vertices in the network that are connected to one and only one input) and their placement to control a long-term power-law memory dynamical network given a specific time-horizon, which we define as the ‘time-to-control’. Remarkably, we provide evidence that long-term power-law memory dynamical networks require considerably fewer driven nodes to steer the network’s state to a desired goal for any given time-to-control as compared with Markov dynamical networks. Finally, our method can be used as a tool to determine the existence of long-term memory dynamics in networks.
Green synthesis of Ag nanoparticle supported on graphene oxide for efficient nitrite sensing in a water sample
Authors: Ezzat Nourhan , Hefnawy Mahmoud A. , Medany Shymaa S. , El-Sherif Rabab M. , Fadlallah Sahar A.
Published: November 2023

Water is essential for conserving biodiversity, ecology, and human health, but because of population growth and declining clean water supplies, wastewater must be treated to meet demand. Nitrite is one of the contaminants in wastewater that is well-known. It is crucial to identify nitrite since it can be fatal to humans in excessive doses. Utilizing a straightforward and effective electrochemical sensor, nitrite in actual water samples may be determined electrochemically. The sensor is created by coating the surface of a GC electrode with a thin layer of graphene oxide (GO), followed by a coating of silver nanoparticles. The modified electrode reached a linear detection range of 1–400 µM. thus, the activity of the electrode was investigated at different pH values ranging from 4 to 10 to cover acidic to highly basic environments. However, the electrode recorded limit of detection (LOD) is equal to 0.084, 0.090, and 0.055 µM for pH 4, 7, and 10, respectively. Additionally, the electrode activity was utilized in tap water and wastewater that the LOD reported as 0.16 and 0.157 µM for tape water and wastewater, respectively.
Categorization of collagen type I and II blend hydrogel using multipolarization SHG imaging with ResNet regression
Authors: Nair Anupama , Lin Chun-Yu , Hsu Feng-Chun , Wong Ta-Hsiang , Chuang Shu-Chun , Lin Yi-Shan , Chen Chung-Hwan , Campagnola Paul , Lien Chi-Hsiang , Chen Shean-Jen
Published: November 2023

Previously, the discrimination of collagen types I and II was successfully achieved using peptide pitch angle and anisotropic parameter methods. However, these methods require fitting polarization second harmonic generation (SHG) pixel-wise information into generic mathematical models, revealing inconsistencies in categorizing collagen type I and II blend hydrogels. In this study, a ResNet approach based on multipolarization SHG imaging is proposed for the categorization and regression of collagen type I and II blend hydrogels at 0%, 25%, 50%, 75%, and 100% type II, without the need for prior time-consuming model fitting. A ResNet model, pretrained on 18 progressive polarization SHG images at 10° intervals for each percentage, categorizes the five blended collagen hydrogels with a mean absolute error (MAE) of 0.021, while the model pretrained on nonpolarization images exhibited 0.083 MAE. Moreover, the pretrained models can also generally regress the blend hydrogels at 20%, 40%, 60%, and 80% type II. In conclusion, the multipolarization SHG image-based ResNet analysis demonstrates the potential for an automated approach using deep learning to extract valuable information from the collagen matrix.
Protective role of CXCR7 activation in neonatal hyperoxia-induced systemic vascular remodeling and cardiovascular dysfunction in juvenile rats
Authors: Benny Merline , Sharma Mayank , Kulandavelu Shathiyah , Chen PingPing , Tian Runxia , Ballengee Sydne , Huang Jiang , Levine Amanda F. , Claure Matteo , Schmidt Augusto F. , Vazquez-Padron Roberto I. , Rodrigues Claudia O. , Wu Shu , Velazquez Omaida C. , Young Karen C.
Published: November 2023

Neonatal hyperoxia induces long-term systemic vascular stiffness and cardiovascular remodeling, but the mechanisms are unclear. Chemokine receptor 7 (CXCR7) represents a key regulator of vascular homeostasis and repair by modulating TGF-β1 signaling. This study investigated whether pharmacological CXCR7 agonism prevents neonatal hyperoxia-induced systemic vascular stiffness and cardiac dysfunction in juvenile rats. Newborn Sprague Dawley rat pups assigned to room air or hyperoxia (85% oxygen), received CXCR7 agonist, TC14012 or placebo for 3 weeks. These rat pups were maintained in room air until 6 weeks when aortic pulse wave velocity doppler, cardiac echocardiography, aortic and left ventricular (LV) fibrosis were assessed. Neonatal hyperoxia induced systemic vascular stiffness and cardiac dysfunction in 6-week-old rats. This was associated with decreased aortic and LV CXCR7 expression. Early treatment with TC14012, partially protected against neonatal hyperoxia-induced systemic vascular stiffness and improved LV dysfunction and fibrosis in juvenile rats by decreasing TGF-β1 expression. In vitro, hyperoxia-exposed human umbilical arterial endothelial cells and coronary artery endothelial cells had increased TGF-β1 levels. However, treatment with TC14012 significantly reduced the TGF-β1 levels. These results suggest that dysregulation of endothelial CXCR7 signaling may contribute to neonatal hyperoxia-induced systemic vascular stiffness and cardiac dysfunction.
Functional analysis of a putative HER2-associated expressed enhancer, Her2-Enhancer1, in breast cancer cells
Authors: Rojhannezhad Mahdieh , Soltani Bahram M. , Vasei Mohammad , Ghorbanmehr Nassim , Mowla Seyed Javad
Published: November 2023

HER-2/neu (HER2) is a member of the epidermal growth factor receptors family, encoding a protein with tyrosine kinase activity. Following the gene amplification or increased HER2 transcription, carcinogenesis has been observed in some cancers. Genetic and epigenetic changes occurring in enhancer sequences can deeply affect the expression and transcriptional regulation of downstream genes, which can cause some physiological and pathological changes, including tumor progression. A therapeutic approach that directly targets the genomic sequence alterations is of high importance, with low side effects on healthy cells. Here, we employed the CRISPR/Cas9 method to genetically knockout an expressed putative enhancer (GH17J039694; we coined it as Her2-Enhancer1) located within the HER2 gene, 17q12: 39,694,339–39,697,219 (UCSC-hg38). We then investigated the potential regulatory effect of Her2-Enhancer1 on HER2 and HER2-interacting genes. To evaluate the cis and trans effects of Her2-Enhancer1, genetic manipulation of this region was performed in HER2-positive and -negative breast cancer cells. Our bioinformatics and real-time PCR data revealed that this putative enhancer region is indeed expressed, and acts as an expressed enhancer. Further functional analysis on edited and unedited cells revealed a significant alteration in the expression of HER2 variants, as well as some other target genes of HER2. Moreover, the apoptosis rate was considerably elevated within the edited cells. As we expected, Western blot analysis confirmed a reduction in protein levels of HER2, GRB7, the gene interacting with HER2, and P-AKT in the PI3K/AKT pathway. Altogether, our findings revealed an enhancer regulatory role for Her2-Enhancer1 on HER2 and HER2-interacting genes; and that this region has a potential for targeted therapy of HER2-positive cancers.
Degumming and characterization of Bombyx mori and non-mulberry silks from Saturniidae silkworms
Authors: Schmidt Theresa , Puchalla Nils , Schendzielorz Marcel , Kramell Annemarie E.
Published: November 2023

In this study, cocoons and degummed silk samples of Bombyx mori and twenty Saturniidae species of the genera Actias, Attacus, Argema, Antheraea, Caligula, Callosamia, Cricula, Epiphora, Hyalophora, Loepa, Samia and Saturnia are studied to gain an insight into their morphology, chemical composition and physical structure. For this purpose, silk samples are characterized by optical microscopy and FTIR spectroscopy in attenuated total reflection mode (ATR-FTIR spectroscopy). Furthermore, degummed silk samples are analyzed for their amino acid (AA) composition by GC-FID. In the course of method development, various degumming methods are tested using alkalis, citric acid, enzymes and detergents. A mixture of 0.1% sodium carbonate and 2.5% ethylenediamine proves to be an effective agent for degumming Saturniidae and B. mori cocoons. After hydrolysis of the fibroin filaments with 6 N hydrochloric acid and derivatization with propyl chloroformate, fifteen AAs are identified and qualified. This method shows a satisfactory overall analytical performance with an average recovery rate of 95% at the medium concentration level. The chemical composition of the different silks was considered comparatively. Within a genus, the analyses usually show a high degree of similarity in AA composition and the resulting structural indices, whereas differences are found between genera.
Network analysis identifies circulating miR-155 as predictive biomarker of type 2 diabetes mellitus development in obese patients: a pilot study
Authors: Catanzaro Giuseppina , Conte Federica , Trocchianesi Sofia , Splendiani Elena , Bimonte Viviana Maria , Mocini Edoardo , Filardi Tiziana , Po Agnese , Besharat Zein Mersini , Gentile Maria Cristina , Paci Paola , Morano Susanna , Migliaccio Silvia , Ferretti Elisabetta
Published: November 2023

Obesity is the main risk factor for many non-communicable diseases. In clinical practice, unspecific markers are used for the determination of metabolic alterations and inflammation, without allowing the characterization of subjects at higher risk of complications. Circulating microRNAs represent an attractive approach for early screening to identify subjects affected by obesity more at risk of developing connected pathologies. The aim of this study was the identification of circulating free and extracellular vesicles (EVs)-embedded microRNAs able to identify obese patients at higher risk of type 2 diabetes (DM2). The expression data of circulating microRNAs derived from obese patients (OB), with DM2 (OBDM) and healthy donors were combined with clinical data, through network-based methodology implemented by weighted gene co-expression network analysis. The six circulating microRNAs overexpressed in OBDM patients were evaluated in a second group of patients, confirming the overexpression of miR-155-5p in OBDM patients. Interestingly, the combination of miR-155-5p with serum levels of IL-8, Leptin and RAGE was useful to identify OB patients most at risk of developing DM2. These results suggest that miR-155-5p is a potential circulating biomarker for DM2 and that the combination of this microRNA with other inflammatory markers in OB patients can predict the risk of developing DM2.
Treatment with a Lactococcus lactis that chromosomally express E. coli cfaI mitigates salivary flow loss in a Sjögren’s syndrome-like disease
Authors: Akgul Ali , Freguia Christian Furlan , Maddaloni Massimo , Hoffman Carol , Voigt Alexandria , Nguyen Cuong Q. , Fanger Neil A. , Fanger Gary R. , Pascual David W.
Published: November 2023

Sjögren’s Syndrome (SjS) results in loss of salivary and lacrimal gland excretion due to an autoimmune attack on these secretory glands. Conventional SjS treatments address the symptoms, but not the cause of disease. Recognizing this deficit of treatments to reverse SjS disease, studies were pursued using the fimbriae from enterotoxigenic E. coli, colonization factor antigen I (CFA/I), which has anti-inflammatory properties. To determine if CFA/I fimbriae could attenuate SjS-like disease in C57BL/6.NOD-Aec1Aec2 (SjS) females, the Lactococcus lactis (LL) 301 strain was developed to chromosomally express the cfaI operon. Western blot analysis confirmed CFA/I protein expression, and this was tested in SjS females at different stages of disease. Repeated dosing with LL 301 proved effective in mitigating salivary flow loss and in reducing anti-nuclear antibodies (ANA) and inflammation in the submandibular glands (SMGs) in SjS females and in restoring salivary flow in diseased mice. LL 301 treatment reduced proinflammatory cytokine production with concomitant increases in TGF-β+ CD25+ CD4+ T cells. Moreover, LL 301 treatment reduced draining lymph and SMG follicular T helper (Tfh) cell levels and proinflammatory cytokines, IFN-γ, IL-6, IL-17, and IL-21. Such evidence points to the therapeutic capacity of CFA/I protein to suppress SjS disease and to have restorative properties in combating autoimmune disease.
Behavioral, neural and ultrastructural alterations in a graded-dose 6-OHDA mouse model of early-stage Parkinson's disease
Authors: Slézia Andrea , Hegedüs Panna , Rusina Evgeniia , Lengyel Katalin , Solari Nicola , Kaszas Attila , Balázsfi Diána , Botzanowski Boris , Acerbo Emma , Missey Florian , Williamson Adam , Hangya Balázs
Published: November 2023

Studying animal models furthers our understanding of Parkinson’s disease (PD) pathophysiology by providing tools to investigate detailed molecular, cellular and circuit functions. Different versions of the neurotoxin-based 6-hydroxydopamine (6-OHDA) model of PD have been widely used in rats. However, these models typically assess the result of extensive and definitive dopaminergic lesions that reflect a late stage of PD, leading to a paucity of studies and a consequential gap of knowledge regarding initial stages, in which early interventions would be possible. Additionally, the better availability of genetic tools increasingly shifts the focus of research from rats to mice, but few mouse PD models are available yet. To address these, we characterize here the behavioral, neuronal and ultrastructural features of a graded-dose unilateral, single-injection, striatal 6-OHDA model in mice, focusing on early-stage changes within the first two weeks of lesion induction. We observed early onset, dose-dependent impairments of overall locomotion without substantial deterioration of motor coordination. In accordance, histological evaluation demonstrated a partial, dose-dependent loss of dopaminergic neurons of substantia nigra pars compacta (SNc). Furthermore, electron microscopic analysis revealed degenerative ultrastructural changes in SNc dopaminergic neurons. Our results show that mild ultrastructural and cellular degradation of dopaminergic neurons of the SNc can lead to certain motor deficits shortly after unilateral striatal lesions, suggesting that a unilateral dose-dependent intrastriatal 6-OHDA lesion protocol can serve as a successful model of the early stages of Parkinson’s disease in mice.
Competing length scales and 2D versus 3D dimensionality in relatively thick superconducting NbN films
Authors: Belogolovskii Mikhail , Poláčková Magdaléna , Zhitlukhina Elena , Grančič Branislav , Satrapinskyy Leonid , Gregor Maroš , Plecenik Tomáš
Published: November 2023

Magneto-transport characteristics of 2D and 3D superconducting layers, in particular, temperature and angular dependences of the upper critical field Hc2, are usually considered to be fundamentally different. In the work, using non-local resistance measurements at temperatures near the normal-to-superconducting transition, we probed an effective dimensionality of nm-thick NbN films. It was found that in relatively thick NbN layers, the thicknesses of which varied from 50 to 100 nm, the temperature effect on Hc2 certainly pointed to the three-dimensionality of the samples, while the angular dependence of Hc2 revealed behavior typical for 2D samples. The seeming contradiction is explained by an intriguing interplay of three length scales in the dimensionally confined superconducting films: the thickness, the Ginzburg–Landau coherence length, and the magnetic-field penetration depth. Our results provide new insights into the physics of superconducting films with an extremely large ratio of the London penetration depth to the Ginzburg–Landau coherence length exhibiting simultaneously 3D isotropic superconducting properties and the 2D transport regime.
An effective method for culturing functional human corneal endothelial cells using a xenogeneic free culture medium
Authors: Alonso-Alonso S. , Vázquez N. , Chacón M. , Caballero-Sánchez N. , Del Olmo-Aguado S. , Suárez C. , Alfonso-Bartolozzi B. , Fernández-Vega-Cueto L. , Nagy L. , Merayo-Lloves J. , Meana A.
Published: November 2023

Endothelial dysfunction is a leading cause of corneal blindness in developed countries and the only available treatment is the endothelial transplantation. However, the limited availability of suitable donors remains a significant challenge, driving the exploration of alternative regenerative therapies. Advanced Therapy Medicinal Products show promise but must adhere to strict regulations that prohibit the use of animal-derived substances. This study investigates a novel culture methodology using Plasma Rich in Growth Factors (PRGF) as the only source of growth factors for primary cultures of human corneal endothelial cells (CECs). CECs were obtained from discarded corneas or endothelial rings and cultured in two different media: one supplemented with xenogeneic factors and other xenogeneic-free, using PRGF. Comprehensive characterization through immunofluorescence, morphological analyses, trans-endothelial electrical resistance measurements, RNA-seq, and qPCR was conducted on the two groups. Results demonstrate that CECs cultured in the xenogeneic-free medium exhibit comparable gene expression, morphology, and functionality to those cultured in the xenogeneic medium. Notably, PRGF-expanded CECs share 46.9% of the gene expression profile with native endothelium and express all studied endothelial markers. In conclusion, PRGF provides an effective source of xenogeneic-free growth factors for the culture of CECs from discarded corneal tissue. Further studies will be necessary to demonstrate the applicability of these cultures to cell therapies that make clinical translation possible.