Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrated Serum Metabolomics and Network Pharmacology Approach to Reveal the Potential Mechanisms of Diwuyanggan Prescription in the Prevention of Acute Liver Injury

Objective: Acute liver injury (ALI) has become a major reason for emergency liver transplantation mortality worldwide. Diwuyanggan (DWYG), a hospital preparation of traditional chinese medicine, does a satisfactory job of treating liver disease, but its pharmacological mechanisms should be further investigated. Thus, we aimed to unravel the mechanisms of DWYG against ALI through a comprehensive approach integrating metabolomics and network pharmacology analysis in this study. Methods: An untargeted metabolomics based on ultra-high pressure liquid chromatography together with quadrupole time of flight mass spectrometry was applied to identify differential metabolites between normal mice and thioacetamide (TAA)-induced ALI mice. By utilizing network pharmacology, potential targets against ALI caused by TAA were excavated. Subsequently, the key targets were validated by real-time polymerase chain reaction assays. Results: DWYG alleviated TAA-induced ALI. Furthermore, 28 differential metabolites were identified with an association between ALI pathological processes and DWYG effects. The pathways involved in bile acid, glycerophospholipid, fatty acid, sphingolipid, tryptophan, and tyrosine metabolism. Then, we found 127 active compounds in DWYG and 26 hub genes associated with the treatment of ALI according to network pharmacology. Besides, according to Kyoto Encyclopedia of Genes and Genome analysis, sphingolipid signaling pathway was deemed as one of the main signaling pathways involved in DWYG anti-ALI, which was in agreement with the metabolomics findings. Further, a combined analysis was performed focusing on 7 key targets, including mitogen-activated protein kinase 1, mitogen-activated protein kinase 8, caspase 3, peroxisome proliferator-activated receptor gamma, albumin, carboxylesterase 1 and glucocerebrosidase, along with their related core metabolites and pathways. Confirmatory experiment further showed that DWYG could reverse the abnormal mRNA expression of these targets in TAA mice. Conclusion: This study revealed direct evidence for the preventive effect of DWYG against ALI and the related pharmacological mechanisms.
Open innovation, dynamic organizational capacities and innovation performance in SMEs: Empirical evidence in the Tunisian manufacturing industry

In this paper, the main objective is to examine inbound open innovation adoption by exploring its antecedents in terms of dynamic organizational capabilities, its implications on innovation performance, but also its mediating role between these capabilities and Small and Medium Enterprise (SME) innovation performance. Therefore, a conceptual model was proposed and empirically tested on the basis of data extracted from a survey involving a sample of 228 Tunisian manufacturing SMEs and analyzed through the Structural Equation Modeling method. In doing so, this paper adds to the existing literature on open innovation in SMEs and fills a neglected theoretical gap by proposing a link between dynamic capabilities theory and the open innovation paradigm, two literatures that have little overlap, to improve current understanding of innovation performance in SMEs. Ultimately, by empirically confirming the significant relationship between dynamic organizational capacities and innovation performance through the mediating role of open innovation, our results are mainly relevant for entrepreneurs and innovation managers in SMEs who can find valuable guidance on how to strengthen innovation performance under the nexus between the dynamic capabilities perspective and open innovation by focusing on the development of three capabilities that are dynamic capabilities, absorptive capability, and appropriation capabilities.
Gender byline bias in sports reporting: Examining the visibility and audience perception of male and female journalists in sports coverage

Gender-based marginalization and discrimination in sports journalism is an ongoing concern of research addressing gender equality in journalism. The visibility of female reporters as authors in terms of sports coverage has been found to be under 10% in content analysis that spans several countries. Research into audiences’ perceptions of authorship in sports journalism further found female authors to be prone to byline biases—even though findings are mixed. In this article, we set out to examine if the under representation of female sport authors has changed over the time span of 15 years. This is explored by conducting a content analysis of news coverage from 2006 to 2020 (Study 1). Further, we study whether biases against female authors in sports coverage (still) exist among recipients and in how far this is different for male and female sports. To address audience perceptions of gender in sport reporting, we performed an online experiment investigating the effect of female and male authorship as well as men’s and women’s football (soccer) as one of the most popular topic of sport reporting (Study 2). We found that female authorship in sports journalism is still marginalized without any significant improvement observed from 2006 to 2020 (Study 1). This contrasts with our findings on audiences’ perceptions of male and female authors, which did not confirm a gender byline bias (Study 2). Our results therefore suggest that gender discrimination in newsrooms cannot be justified by audience perceptions.
Periodic impulsive fractional differential equations

Abstract This paper deals with the existence of periodic solutions of fractional differential equations with periodic impulses. The first part of the paper is devoted to the uniqueness, existence and asymptotic stability results for periodic solutions of impulsive fractional differential equations with varying lower limits for standard nonlinear cases as well as for cases of weak nonlinearities, equidistant and periodically shifted impulses. We also apply our result to an impulsive fractional Lorenz system. The second part extends the study to periodic impulsive fractional differential equations with fixed lower limit. We show that in general, there are no solutions with long periodic boundary value conditions for the case of bounded nonlinearities.
Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19

Abstract It is predictable that the renin–angiotensin–aldosterone and kinin–kallikrein systems are dysregulated in COVID-19 (COV) patients because SARS-CoV-2 requires ACE2 to cause an infection. This study aimed to assess the serum levels of des-arg(9)-bradykinin (DABK) and angiotensin 1–7 (ang-(1–7)) in patients with COV who had the above-mentioned cardiovascular disease risk factors. In a cross-sectional study, 69 COV patients were selected among patients referred to the main referral center for these patients, in Kerman, Iran, and 73 matched control (non-COV) individuals among individuals who participated in the KERCARD cohort study. Serum levels of DABK and ang-(1–7) were measured by ELISA in the groups of CTL (healthy), HTN, DM, OB, COV, COV + HTN, COV + DM, and COV + OB. Ang-(1–7) levels were lower in the COV + HTN group compared to the HTN group. DABK levels were higher in the COV, HTN, and OB groups and in DM + COV subjects compared to their corresponding control group. The levels of ang-(1–7) and DABK were related to HTN and OB, respectively. According to the findings, we can infer that an increase in DABK production in those with the cardiovascular disease risk factors of diabetes, obesity, and hypertension or a decrease in ang-(1–7) in those with hypertension may contribute to the adverse outcomes of SARS-CoV-2 infection.
Online Algebraic Identification Approach of Continuous Linear Time Delay Systems

In this paper, we propose an online algebraic method to identify linear continuous time delay process from step response, in presence of unknown initial state and constant load disturbance. The identification mechanism is split into two sequential steps. The time delay and dynamic of the plant is estimated firstly through a spectral formulation. In the next stage, the transient regime is deduced from a linear regression. To improve the robustness of the proposed method, a local convolution by sigmoid function is proposed. Simulation results are provided, at last, to show the effectiveness of our conceived approach.
AbsIntIO: Towards Showing the Absence of Integer Overflows in Binaries using Abstract Interpretation

In the past years, the CWE-190 integer overflow led to many vulnerabilities. Program verification techniques such as Abstract Interpretation can show that no such bug is present in a given program. To date, such techniques often aim to verify the correctness of source code. However, as the source code is not always available or might not have been subject to such an analysis, it is advisable to apply abstract integer range analysis to the binary. However, analyzing binaries imposes other challenges which are not always addressed accurately by existing analysis tools. As an example, some tools fail to model bitwise operators, recover type information or do not account for compiler optimizations. We propose techniques to address these limitations and illustrate their effects in our configurable reference implementation AbsIntIO. AbsIntIO applies abstract integer range analysis to binaries with the goal to show that no integer overflow is possible. We evaluate the effects of the improvements and observed a reduction of the error rates. Hence, the improvements provide a step towards verifying the correctness of binaries.
Global Diversity in Mammalian Life Histories: Environmental Realms and Evolutionary Adaptations

Mammalian life history strategies can be characterized by a few axes of variation, which conform a space where species are positioned according to which life history strategies are favoured in the environment they exploit. Yet, we still lack global descriptions of the diversity of realized mammalian life history and of how this diversity is shaped by the environment. We used six life history traits to build a global life history space and explored how major environmental realms (land, air, water) influence mammalian life history strategies. We demonstrate that realms are tightly linked to distinct life history strategies. Predominantly, aquatic and aerial species adhere to slower life history strategies, while terrestrial species tend to exhibit faster life histories. Highly encephalized terrestrial species are a notable exception to these patterns. In addition, species transitioning between the terrestrial and aquatic realms, such as seals, show intermediate life history strategies. Further, different mode-of-life may play a significant role in allowing to expand the set of strategies exploitable in the terrestrial realm. Our results provide compelling evidence of the link between environmental realms and the diversity of life history strategies among mammals. Statement of authorship P.C. L. , R.S-G. , and C.P.C. conceived the core ideas behind this paper, all authors provided fundamental inputs for its final development. E.B collected all data and performed the literature search needed to sort species in environmental realms. E.B. analysed the data with fundamental inputs from C.P.C. , P.C. L, and R.G-S. All authors contributed to interpretation of the results. E.B. and C.P.C. led the writing of the manuscript which was edited by all authors.
Complete zooplankton size spectra re-constructed from « in situ » imaging and Multinet data in the global ocean

Plankton size spectra are important indicators of the ecosystem state, as they illustrate the quantity of organisms available for higher marine food web and reflect multiple size-dependent processes. Yet, such measurements are typically biased by the available sampling methods, either disrupting fragile organisms or lacking good resolution (in size and/or time and space). In this study, we combined two of the most common approaches to measure zooplankton Normalized Biomass/Biovolume Size Spectra (NBSS) to calculate a complete zooplankton distribution for organisms larger than 1 mm. The reconstructed NBSS slopes appeared steeper and closer to those measured by the UVP5 (+7.6%) and flatter than those of the Multinet (- 20%) particularly in tropics and temperate latitudes. The overall gain in polar biomass was relatively small for reconstructed biomass compared to bulk estimates from Multinet (+0.24 mgC/m3 or +4.25%) and high from the UVP5 (+2.0 mgC/m3 or +53%). In contrast, in the tropical and temperate ecosystems, the gain in biomass was small for UVP5 (+0.67 mgC/m3 or +30.44% and +0.74 mgC/m3 or +19.59% respectively) and high for Multinet (+1.66 mgC/m3 or +136% and +3.4 mgC/m3 or +309% respectively). Given these differences, we suggest here to combine in situ imaging sensors and net data in any comprehensive study exploring key living players in the ocean ecosystem and their contributions to the biological pump.
Genomic refugium of pre-domestication lineages in the Bronze Age Carpathian Basin

Horse domestication is a key element in history for its impact on human mobility and warfare. There is clear evidence for horse control from the beginning of the 2nd millennium BCE in the Carpathian Basin, when antler cheekpieces appear in the archaeological record mostly in the eastern areas. Previous archaeogenomic studies also revealed that the spread of the ancestors of modern day horses began at this time period, but the details of this event in Bronze Age Europe is yet to be uncovered. In this study we report a new shotgun genome (∼0.9x coverage) of a Middle Bronze Age horse (radiocarbon dated to 1740-1630 cal. BCE) from Tompa site, southern Hungary, along with six mitochondrial genomes from various sites from Late Copper Age to Early Bronze Age Western Hungary. Our results reveal a strong bottleneck among pre-domestication Carpathian Basin horses and delayed DOM2 introduction into the region compared to the surrounding areas. The population size reduction was most probably due to human mediated loss of natural habitat, but the practice of horsekeeping after the turn of the 2nd millennium BCE can not be excluded based on the genomic data. Our results provide a complex history for horse domestication in the Central-European region, highlighting the need for further research to fully understand the extent and nature of human-horse interactions in this area throughout prehistory.
Neuronal wiring diagram of an adult brain

Connections between neurons can be mapped by acquiring and analyzing electron microscopic (EM) brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative, yet inadequate for understanding brain function more globally. Here, we present the first neuronal wiring diagram of a whole adult brain, containing 5×107 chemical synapses between ∼130,000 neurons reconstructed from a female Drosophila melanogaster. The resource also incorporates annotations of cell classes and types, nerves, hemilineages, and predictions of neurotransmitter identities. Data products are available by download, programmatic access, and interactive browsing and made interoperable with other fly data resources. We show how to derive a projectome, a map of projections between regions, from the connectome. We demonstrate the tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine, and descending neurons), across both hemispheres, and between the central brain and the optic lobes. Tracing from a subset of photoreceptors all the way to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviors. The technologies and open ecosystem of the FlyWire Consortium set the stage for future large-scale connectome projects in other species.
Profiling of Zea mays L. proteome at early stages of compatible interactions with Meloidogyne arenaria indicates changes in signaling, oxidative stress responses, and S-adenosylmethionine biosynthesis

Root-knot nematodes (RKNs) are distributed worldwide group of plant parasitic nematodes, with a very wide host range, including mono- and dicotyledonous hosts. Meloidogyne arenaria is, next to M. hapla, M. incognita, and M. javanica, one of the most economically important species from this genus. RKNs during parasitism hijack host metabolism to establish giant cells and to break down plant defense mechanisms. To date, studies on the interaction of RKN with maize (Zea mays L.) have been underrepresented, and a description of the early response to attack by these nematodes, vital to understanding the process, is scarce in the literature. We hypothesize that in the early stage of maize response to M. arenaria infection, significant changes in the accumulation level of proteins mainly related to plant defense response, plant cell wall modifications, and phytohormone biosynthesis can be observed. In this study, a mass spectrometry approach and a label-free quantification technique were used to assess the qualitative and quantitative composition of proteins changes in the proteome of maize roots after M. arenaria infection. We used a susceptible maize variety and carried out analyses of plant proteome at two time points: 24 hours after nematode inoculation and 3 days after inoculation. Statistical analyses of significant differences between protein intensities were performed for the datasets obtained from healthy and M. arenaria-infected plants, and differentially expressed proteins (DEPs), with both lower and higher abundance were determined. DEPs were mapped, classified to the gene ontology (GO) terms into functional categories, and assigned to appropriate Kyoto Encyclopedia of Genes and Genomes (KEGG) processes and pathways. As a result, a total of 3,743 proteins were identified with 124 DEPs at 24 hpi and 66 at 3 dpi, and significant changes in the accumulation of proteins associated with processes such as cell wall modifications, reaction to stress, as well as processes and pathways related to phenylpropanoid biosynthesis and metabolism, signal transduction and to S-adenosylmethionine biosynthesis.
Vibrio cholerae Arrests Intestinal Epithelial Proliferation through T6SS-dependent Activation of the Bone Morphogenetic Protein Pathway

To maintain an effective barrier, intestinal epithelial progenitor cells must divide at a rate that matches the loss of dead and dying cells. Otherwise, epithelial breaches expose the host to systemic infection by gut-resident microbes. Unlike most pathogens, Vibrio cholerae blocks tissue repair by arresting progenitor proliferation in the Drosophila infection model. At present, we do not understand how Vibrio circumvents such a critical antibacterial defense. In a series of genetic experiments, we found that V. cholerae blocks epithelial repair by activating the growth inhibitor Bone Morphogenetic Protein (BMP) pathway in progenitors. Specifically, we discovered that interactions between Vibrio and gut commensals initiate BMP signaling via host innate immune defenses. Notably, we found that Vibrio also activates BMP and arrests proliferation in zebrafish intestines, indicating an evolutionarily conserved link between infection, BMP and failure in tissue repair. Combined, our study highlights how enteric pathogens engage host immune and growth regulatory pathways to disrupt intestinal epithelial repair.
A Random Matrix Approach to Single Cell RNA-seq Analysis

Single cell RNA-seq (scRNAseq) workflows typically start with a raw expression matrix and end with the clustering of sampled cells. Viewed broadly, scRNAseq is a signal processing workflow that takes a transcriptional signal as input and outputs a cell clustering. Currently, we lack a quantitative framework through which to describe the input signal and assess the dependence of correct clustering on the signal properties. As a result, fundamental questions regarding the resolution of scRNAseq remain unanswered and experimentalists have little guidance in determining whether a hypothesized cell type will be clustered by a particular scRNAseq experiment. In this work, we define the notion of a transcriptional signal associated with a gene module, show that the tools of random matrix theory can be used to characterize the signal as it moves through a common (PCA-based) scRNAseq workflow, and develop estimates for cell clustering based on the signal properties and, in particular, the signal strength. We give a formula - that can be computed from expression data - for the signal strength, providing a framework through which scRNAseq resolution can be investigated.
Neurophysiological correlates of Somatosensory tinnitus modulation

Background Tinnitus is the subjective perception of a sound without a physical sound source. Neuronal activity in various brain areas contribute to its generation. Research has highlighted somatosensory processes associated with tinnitus. We here investigate if differences in tinnitus perception mediated by the somatosensory system are reflected in brain oscillations. Methods 24 tinnitus patients performed relaxing versus straining exercises with their jaw. After each condition, participants’ brain activity was measured with Magnetoencephalography and participants rated tinnitus loudness and annoyance on visual analogue scales. Brain activity was contrasted for the strained versus relaxed state on sensor level using a cluster-based permutation test. Derived significant clusters were localized using a beamformer approach. Additionally, for every patient and condition a mean loudness and pleasantness score was determined and differences between conditions tested using student’s t-tests. Results After completion of straining compared to relaxing exercises participants experienced their tinnitus as louder and more annoying (p<.05). Tinnitus worsening was accompanied by a significant increase of gamma power (32-46 Hz) showing up mainly in right secondary auditory cortex, and a significant decrease of alpha power (7-14 Hz) peaking in left and right sensorimotor cortex after completion of the straining versus relaxing exercises. Discussion We here show that tinnitus perception can be reduced by preceding relaxing exercises with the jaw. Tinnitus improvement is accompanied by reduced auditory gamma power and increased sensorimotor alpha power. These results point to a functional role of the cortical sensorimotor system in maintaining tinnitus.
AMF-SporeChip provides new insights into arbuscular mycorrhizal fungal pre-symbiotic hyphal growth dynamics at the cellular level

Arbuscular mycorrhizal fungi (AMF) form symbiotic associations with the majority of land plants and deliver a wide range of soil-based ecosystem services. Due to their conspicuous belowground lifestyle in a dark environment surrounded by soil particles, much is still to be learned about the influence of environmental (i.e., physical) cues on spore germination, hyphal morphogenesis and hyphopodium formation in AMF. To fill existing gaps in AMF knowledge, we developed a new microfluidic platform – termed the AMF-SporeChip – to immobilise Rhizophagus and Gigaspora spores and confront pre-symbiotic hyphae with physical obstacles. In combination with timelapse microscopy, the fungi could be examined at the cellular level and in real-time. The AMF-SporeChip allowed us to acquire movies with unprecedented visual clarity and therefore identify various exploration strategies of AMF pre-symbiotic hyphae. We witnessed anastomosis formation involving directed hyphal growth in a “stop-and-go” manner, yielding visual evidence of pre-anastomosis signalling and decision-making. Remarkably, we also revealed a so-far undescribed reversible cytoplasmic retraction as part of a highly dynamic space navigation. Our findings demonstrated how AMF employ an intricate mechanism of space searching, involving reversible cytoplasmic retraction, branching and directional changes. In turn, the AMF-SporeChip is expected to open many future frontiers for AMF research.