Miracle-dz/UniFAR-FTUs huggingface dataset:
Gravity-Vector Induces Mechanical Remodeling of rMSCs via Combined Substrate Stiffness and Orientation

Distinct physical factors originating from the cellular microenvironment are crucial to the biological homeostasis of stem cells. While substrate stiffness and orientation are known to regulate the mechanical remodeling and fate decision of mesenchymal stem cells (MSCs) separately, it remains unclear how the two factors are combined to manipulate their mechanical stability under gravity vector. Here we quantified these combined effects by placing rat MSCs onto stiffness-varied poly-dimethylsiloxane (PDMS) substrates in upward (180°), downward (0°), or edge-on (90°) orientation. Compared with those values onto glass coverslip, the nuclear longitudinal translocation, due to the density difference between the nucleus and the cytosol, was found to be lower at 0° for 24 h and higher at 90° for 24 and 72 h onto 2.5 MPa PDMS substrate. At 0°, the cell was mechanically supported by remarkably reduced actin and dramatically enhanced vimentin expression. At 90°, both enhanced actin and vimentin expression worked cooperatively to maintain cell stability. Specifically, perinuclear actin stress fibers with a large number, low anisotropy, and visible perinuclear vimentin cords were formed onto 2.5 MPa PDMS at 90° for 72 h, supporting the orientation difference in nuclear translocation and global cytoskeleton expression. This orientation dependence tended to disappear onto softer PDMS, presenting distinctive features in nuclear translocation and cytoskeletal structures. Moreover, cellular morphology and focal adhesion were mainly affected by substrate stiffness, yielding a time course of increased spreading area at 24 h but decreased area at 72 h with a decrease of stiffness. Mechanistically, the cell tended to be stabilized onto these PDMS substrates via β1 integrin–focal adhesion complexes–actin mechanosensitive axis. These results provided an insight in understanding the combination of substrate stiffness and orientation in defining the mechanical stability of rMSCs.
Predicting Spike Features of Hodgkin-Huxley-Type Neurons With Simple Artificial Neural Network

Hodgkin-Huxley (HH)-type model is the most famous computational model for simulating neural activity. It shows the highest accuracy in capturing neuronal spikes, and its model parameters have definite physiological meanings. However, HH-type models are computationally expensive. To address this problem, a previous study proposed a spike prediction module (SPM) to predict whether a spike will take place 1 ms later based on three voltage values with intervals of 1 ms. Although SPM does well, it fails to evaluate the informative features of the spike. In this study, the feature prediction module (FPM) based on simple artificial neural network (ANN) was proposed to predict spike features including maximum voltage, minimum voltage, and dropping interval. Nine different HH-type models were adopted whose firing patterns cover most of the firing behaviors observed in the brain. Voltage and spike feature samples under constant external input current were collected for training and testing. Experiment results illustrated that the combination of SPM and FPM can accurately predict the spiking part of different HH-type models and can generalize to unseen types of input current. The combination of SPM and FPM may offer a possible way to simulate the action potentials of biological neurons with high accuracy and efficiency.
Myxococcus xanthus R31 Suppresses Tomato Bacterial Wilt by Inhibiting the Pathogen Ralstonia solanacearum With Secreted Proteins

The pathogenic bacterium Ralstonia solanacearum caused tomato bacterial wilt (TBW), a destructive soil-borne disease worldwide. There is an urgent need to develop effective control methods. Myxobacteria are microbial predators and are widely distributed in the soil. Compared with other biocontrol bacteria that produce antibacterial substances, the myxobacteria have great potential for biocontrol. This study reports a strain of Myxococcus xanthus R31 that exhibits high antagonistic activity to R. solanacearum. Plate test indicated that the strain R31 efficiently predated R. solanacearum. Pot experiments showed that the biocontrol efficacy of strain R31 against TBW was 81.9%. Further study found that the secreted protein precipitated by ammonium sulfate had significant lytic activity against R. solanacearum cells, whereas the ethyl acetate extract of strain R31 had no inhibitory activity against R. solanacearum. Substrate spectroscopy assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of secreted proteins showed that some peptidases, lipases, and glycoside hydrolases might play important roles and could be potential biocontrol factors involved in predation. The present study reveals for the first time that the use of strain M. xanthus R31 as a potential biocontrol agent could efficiently control TBW by predation and secreting extracellular lyase proteins.
Individual and Contextual Influences on the Start-up Inclination of Women Academics

Although in recent years there has been an increasing interest in studies of academic entrepreneurship, only a few studies investigating the start-up inclination of women working in academia have been reported. This paper investigates intention formation, person input, and contextual factors as predictors for the start-up inclination of academic women at German universities based on the Social Cognitive Career Theory (SCCT). We employ multinomial logistic regression in a sequential analysis. Our data refers to the sample from the “Institut für Mittelstandsforschung” “IfM” Bonn, Germany. Thus, we conduct a secondary analysis. The sample size considered for academic women is 2,340. Person input shows mixed effects on the start-up inclination. Contextual factors; however, exert a positive impact on having a start-up idea among academic females in Germany. Intention formation has a positive influence on having a concrete and non-concrete start-up idea. Our paper intends to fill the research gap by adding to the available models explaining individual and contextual factors that influence having a start-up idea a SCCT-based model that explains the start-up inclination of women working in academia.
Lichenysin Production by Bacillus licheniformis Food Isolates and Toxicity to Human Cells

Bacillus licheniformis can cause foodborne intoxication due to the production of the surfactant lichenysin. The aim of this study was to measure the production of lichenysin by food isolates of B. licheniformis in LB medium and skimmed milk and its cytotoxicity for intestinal cells. Out of 11 B. licheniformis isolates tested, most showed robust growth in high salt (1M NaCl), 4% ethanol, at 37 or 55°C, and aerobic and anaerobic conditions. All strains produced lichenysin (in varying amounts), but not all strains were hemolytic. Production of this stable compound by selected strains (high producers B4094 and B4123, and type strain DSM13T) was subsequently determined using LB medium and milk, at 37 and 55°C. Lichenysin production in LB broth and milk was not detected at cell densities < 5 log10 CFU/ml. The highest concentrations were found in the stationary phase of growth. Total production of lichenysin was 4–20 times lower in milk than in LB broth (maximum 36 μg/ml), and ∼10 times lower in the biomass obtained from milk agar than LB agar. Under all conditions tested, strain B4094 consistently yielded the highest amounts. Besides strain variation and medium composition, temperature also had an effect on lichenysin production, with twofold lower amounts of lichenysin produced at 55°C than at 37°C. All three strains produced lichenysin A with varying acyl chain lengths (C11–C18). The relative abundance of the C14 variant was highest in milk and the C15 variant highest in LB. The concentration of lichenysin needed to reduce cell viability by 50% (IC50) was 16.6 μg/ml for Caco-2 human intestinal epithelial cells and 16.8 μg/ml for pig ileum organoids. Taken together, the presence of low levels (<5 log10 CFU/ml) of B. licheniformis in foods is unlikely to pose a foodborne hazard related to lichenysin production. However, depending on the strain present, the composition, and storage condition of the food, a risk of foodborne intoxication may arise if growth to high levels is supported and such product is ingested.
Illness Perceptions and Medication Nonadherence to Immunosuppressants After Successful Kidney Transplantation: A Cross-Sectional Study

Background: Medication nonadherence to immunosuppressants is a well-known risk factor for suboptimal health outcomes in kidney transplant recipients (KTRs). This study examined the relationship between illness perceptions and medication nonadherence in prevalent Dutch KTRs and whether this relationship depended on post-transplant time. Methods: Eligible KTRs transplanted in Leiden University Medical Center were invited for this cross-sectional study. The illness perceptions and medication nonadherence were measured via validated questionnaires. Associations between illness perceptions and medication nonadherence were investigated using multivariable logistic regression models. Results: For the study, 627 participating KTRs were analyzed. 203 (32.4%) KTRs were considered nonadherent to their immunosuppressants with “taking medication more than 2 h from the prescribed dosing time” as the most prevalent nonadherent behaviour (n = 171; 27.3%). Three illness perceptions were significantly associated with medication nonadherence: illness identity (adjusted odds ratio [ORadj] = 1.07; 95% confidence interval [CI], 1.00–1.14), concern (ORadj = 1.07; 95%CI,1.00–1.14), and illness coherence (ORadj = 1.11; 95%CI,1.01–1.22). The relationships between illness perceptions and medication nonadherence did not differ depending on post-transplant time (p-values ranged from 0.48 to 0.96). Conclusion: Stronger negative illness perceptions are associated with medication nonadherence to immunosuppressants. Targeting negative illness perceptions by means of psychoeducational interventions could optimize medication adherence and consequently improve health outcomes in KTRs.
Can China's New Rural Cooperative Medical System Improve Farmers' Subjective Well-Being?

The New Rural Cooperative Medical System (NRCMS) is one of the essential systems for ensuring public health in rural China. This paper investigates the effect of farmers' participation in the NRCMS on their subjective well-being and its mechanisms using data from the Chinese General Social Survey 2017. The results show that farmers' participation in the NRCMS significantly enhances their subjective well-being, and these results remain robust after regression with the instrumental variables method and propensity score matching method. Further analysis of the mechanisms suggests that participation in the NRCMS can enhance farmers' subjective well-being by increasing their consumption levels other than medical consumption. Moreover, medical consumption levels play a negative role in participating in the NRCMS on farmers' subjective well-being, which can be explained as the “masking effect. ” The regression results of the subsamples show that the higher a farmer's income is, the less his or her participation in the NRCMS enhances subjective well-being. And the effect of participation in the NRCMS on farmers' subjective well-being is not significant if their health status is too high or too low.
Comprehensive Characterization of Pyroptosis Patterns with Implications in Prognosis and Immunotherapy in Low-Grade Gliomas

Background: Due to high heterogeneity and mortality of low-grade gliomas (LGGs), it is of great significance to find biomarkers for prognosis and immunotherapy. Pyroptosis is emerging as an attractive target in cancer research for its effect on tumor immune microenvironment (TIME). However, the investigation of pyroptosis in LGGs is insufficient. Methods: LGG samples from TCGA and CGGA database were classified into two pyroptosis patterns based on the expression profiles of 52 PRGs using consensus clustering. A prognostic model was constructed by using the LASSO-COX method. ESTIMATE algorithm and single sample gene set enrichment analysis (ssGSEA) were used to characterize the TIME. Based on the differentially expressed genes between two pyroptosis patterns, favorable and unfavorable pyroptosis gene signatures were determined. Pyroptosis score scheme was constructed to quantify the pyroptosis patterns through gene set variation analysis (GSVA) method. Two external datasets and immunotherapy cohort from CGGA and GEO database were used to validate the predictive value of the pyroptosis score. The Human Protein Atlas website and Western blotting were utilized to confirm the expression of the selected genes in the prognostic model in LGGs. Results: Distinct overall survival and immune checkpoint blockage therapeutic responses were identified between two pyroptosis patterns. A low pyroptosis score in LGG patients implies higher overall survival, poor immune cell infiltration, and better response to immunotherapy of immune checkpoint blockage. Conclusion: Our findings provided a foundation for future research targeting pyroptosis and opened a new sight to explore the prognosis and immunotherapy from the angle of pyroptosis in LGGs.
Neuromeric Distribution of Nicotinamide Adenine Dinucleotide Phosphate-Diaphorase Activity in the Adult Lamprey Brain

This study reports for the first time the distribution and morphological characterization of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d; a reliable marker of nitric oxide synthase activity) positive elements in the central nervous system of the adult river lamprey (Lampetra fluviatilis) on the framework of the neuromeric model and compares their cytoarchitectonic organization with that of gnathostomes. Both NADPH-d exhibiting cells and fibers were observed in all major divisions of the lamprey brain as well as in the spinal cord. In the secondary prosencephalon, NADPH-d positive cells were observed in the mitral cell layer of the olfactory bulb, evaginated pallium, amygdala, dorsal striatum, septum, lateral preoptic nucleus, caudal paraventricular area, posterior entopeduncular nucleus, nucleus of the stria medullaris, hypothalamic periventricular organ and mamillary region sensu lato. In the lamprey diencephalon, NADPH-d labeled cells were observed in several nuclei of the prethalamus, epithalamus, pretectum, and the basal plate. Especially remarkable was the staining observed in the right habenula and several pretectal nuclei. NADPH-d positive cells were also observed in the following mesencephalic areas: optic tectum (two populations), torus semicircularis, nucleus M5 of Schöber, and a ventral tegmental periventricular nucleus. Five different cell populations were observed in the isthmic region, whereas the large sensory dorsal cells, some cells located in the interpeduncular nucleus, the motor nuclei of most cranial nerves, the solitary tract nucleus, some cells of the reticular nuclei, and small cerebrospinal fluid-contacting (CSF-c) cells were the most evident stained cells of the rhombencephalon proper. Finally, several NADPH-d positive cells were observed in the rostral part of the spinal cord, including the large sensory dorsal cells, numerous CSF-c cells, and some dorsal and lateral interneurons. NADPH-d positive fibers were observed in the olfactory pathways (primary olfactory fibers and stria medullaris), the fasciculus retroflexus, and the dorsal column tract. Our results on the distribution of NADPH-d positive elements in the brain of the adult lamprey L. fluviatilis are significantly different from those previously reported in larval lampreys and demonstrated that these animals possess a complex nitrergic system readily comparable to those of other vertebrates, although important specific differences also exist.
Rapid Detection and Differentiation of Legionella pneumophila and Non-Legionella pneumophila Species by Using Recombinase Polymerase Amplification Combined With EuNPs-Based Lateral Flow Immunochromatography

Legionella, a waterborne pathogen, is the main cause of Legionnaires’ disease. Therefore, timely and accurate detection and differentiation of Legionella pneumophila and non-Legionella pneumophila species is crucial. In this study, we develop an easy and rapid recombinase polymerase amplification assay combined with EuNPs-based lateral flow immunochromatography (EuNPs-LFIC-RPA) to specifically distinguish Legionella pneumophila and non-Legionella pneumophila. We designed primers based on the mip gene of Legionella pneumophila and the 5S rRNA gene of non-Legionella pneumophila. The recombinase polymerase amplification reaction could go to completion in 10 min at 37°C, and the amplification products could be detected within 5 min with EuNPs-LFIC strips. Using a florescent test strip reader, the quantitative results were achieved by reading the colored signal intensities on the strips. The sensitivity was 1.6 × 101 CFU/ml, and a linear standard linear curve plotted from the test strip reader had a correlation coefficient for the determination of Legionella pneumophila (R 2 = 0.9516). Completed concordance for the presence or absence of Legionella pneumophila by EuNPs-LFIC-RPA and qPCR was 97.32% (κ = 0.79, 95% CI), according to an analysis of practical water samples (n = 112). In short, this work shows the feasibility of EuNPs-LFIC-RPA for efficient and rapid monitoring of Legionella pneumophila and non-Legionella pneumophila in water samples.
Network Models and Simulation Analytics for Multi-scale Dynamics of Biological Invasions

Globalization and climate change facilitate the spread and establishment of invasive species throughout the world via multiple pathways. These spread mechanisms can be effectively represented as diffusion processes on multi-scale, spatial networks. Such network-based modeling and simulation approaches are being increasingly applied in this domain. However, these works tend to be largely domain-specific, lacking any graph theoretic formalisms, and do not take advantage of more recent developments in network science. This work is aimed toward filling some of these gaps. We develop a generic multi-scale spatial network framework that is applicable to a wide range of models developed in the literature on biological invasions. A key question we address is the following: how do individual pathways and their combinations influence the rate and pattern of spread? The analytical complexity arises more from the multi-scale nature and complex functional components of the networks rather than from the sizes of the networks. We present theoretical bounds on the spectral radius and the diameter of multi-scale networks. These two structural graph parameters have established connections to diffusion processes. Specifically, we study how network properties, such as spectral radius and diameter are influenced by model parameters. Further, we analyze a multi-pathway diffusion model from the literature by conducting simulations on synthetic and real-world networks and then use regression tree analysis to identify the important network and diffusion model parameters that influence the dynamics.
Peripherical Electrical Stimulation for Parkinsonian Tremor: A Systematic Review

Parkinsonian tremor is one of the most common motor disorders in patients with Parkinson's disease (PD). Compared to oral medications and brain surgery, electrical stimulation approaches have emerged as effective and non-invasive methods for tremor reduction. The pathophysiology, detection and interventions of tremors have been introduced, however, a systematic review of peripherical electrical stimulation approaches, methodologies, experimental design and clinical outcomes for PD tremor suppression is still missing. Therefore, in this paper, we summarized recent studies on electrical stimulation for tremor suppression in PD patients and discussed stimulation protocols and effectiveness of different types of electrical stimulation approaches in detail. Twenty out of 528 papers published from 2010 to 2021 July were reviewed. The results show that electrical stimulation is an efficient intervention for tremor suppression. The methods fall into three main categories according to the mechanisms: namely functional electrical stimulation (FES), sensory electrical stimulation (SES) and transcutaneous electrical nerve stimulation (TENS). The outcomes of tremor suppression were varied due to various stimulation approaches, electrode locations and stimulation parameters. The FES method performed the best in tremor attenuation where the efficiency depends mainly by the control strategy and accuracy of tremor detection. However, the mechanism underlying tremor suppression with SES and TENS, is not well-known. Current electrical stimulation approaches may only work for a number of patients. The potential mechanism of tremor suppression still needs to be further explored.
A Tutorial on Moving Target Defense Approaches Within Automotive Cyber-Physical Systems

Moving Target Defenses (MTD) have become a popular and emerging defense strategy for the protection of traditional information technology systems. By their very nature, MTD strategies are designed to protect against adversary reconnaissance efforts on static platforms, essentially sitting back and having unlimited time to identify, craft, execute, and scale an exploit. With the rapid adoption of distributed automotive Cyber-Physical Systems (CPS) ranging from self driving cars, to connected transportation infrastructure, it is becoming more apparent that third party supply chains, increased remote communication interfaces, and legacy software stacks are making the traditionally designed standalone systems become more susceptible to safety-critical cyber-attacks. MTD strategies within the automotive CPS domain have to delicately balance the tradeoff between security and real time predictability, maintaining the safety constraints of the systems. In this paper, we explore the various MTD strategies presented within the literature while discussing potential applicability and strategies sufficient for the automotive CPS domain.
EZH2 Mediates Proliferation, Migration, and Invasion Promoted by Estradiol in Human Glioblastoma Cells

Glioblastomas (GBM) are the most frequent and aggressive brain tumors. 17β-estradiol (E2) increases proliferation, migration, and invasion of human GBM cells; however underlying mechanisms are no fully understood. Zeste 2 Enhancer Homologous enzyme (EZH2) is a methyltransferase part of Polycomb 2 repressor complex (PRC2). In GBM, EZH2 is overexpressed and involved in the cell cycle, migration, and invasion processes. We studied the role of EZH2 in the pro-oncogenic actions of E2 in human GBM cells. EZH2 gene silencing and pharmacological inhibition of EZH2 blocked proliferation, migration, and invasion of GBM cells induced by E2. We identified in silico additional putative estrogen response elements (EREs) at the EZH2 promoter, but E2 did not modify EZH2 expression. In silico analysis also revealed that among human GBM samples, EZH2 expression was homogeneous; in contrast, the heterogeneous expression of estrogen receptors (ERs) allowed the classification of the samples into groups. Even in the GBM cluster with high expression of ERs and those of their target genes, the expression of PCR2 target genes did not change. Overall, our data suggest that in GBM cells, pro-oncogenic actions of E2 are mediated by EZH2, without changes in EZH2 expression and by mechanisms that appear to be unrelated to the transcriptional activity of ERs.