Miracle-dz/UniFAR-FTUs huggingface dataset:
Remodeling the Epigenetic Landscape of Cancer—Application Potential of Flavonoids in the Prevention and Treatment of Cancer

Epigenetics, including DNA methylation, histone modification, and noncoding RNA regulation, are physiological regulatory changes that affect gene expression without modifying the DNA sequence. Although epigenetic disorders are considered a sign of cell carcinogenesis and malignant events that affect tumor progression and drug resistance, in view of the reversible nature of epigenetic modifications, clinicians believe that associated mechanisms can be a key target for cancer prevention and treatment. In contrast, epidemiological and preclinical studies indicated that the epigenome is constantly reprogrammed by intake of natural organic compounds and the environment, suggesting the possibility of utilizing natural compounds to influence epigenetics in cancer therapy. Flavonoids, although not synthesized in the human body, can be consumed daily and are common in medicinal plants, vegetables, fruits, and tea. Recently, numerous reports provided evidence for the regulation of cancer epigenetics by flavonoids. Considering their origin in natural and food sources, few side effects, and remarkable biological activity, the epigenetic antitumor effects of flavonoids warrant further investigation. In this article, we summarized and analyzed the multi-dimensional epigenetic effects of all 6 subtypes of flavonoids (including flavonols, flavones, isoflavones, flavanones, flavanols, and anthocyanidin) in different cancer types. Additionally, our report also provides new insights and a promising direction for future research and development of flavonoids in tumor prevention and treatment via epigenetic modification, in order to realize their potential as cancer therapeutic agents.
The Interactions Between Candida albicans and Mucosal Immunity

Mucosa protects the body against external pathogen invasion. However, pathogen colonies on the mucosa can invade the mucosa when the immunosurveillance is compromised, causing mucosal infection and subsequent diseases. Therefore, it is necessary to timely and effectively monitor and control pathogenic microorganisms through mucosal immunity. Candida albicans is the most prevalent fungi on the mucosa. The C. albicans colonies proliferate and increase their virulence, causing severe infectious diseases and even death, especially in immunocompromised patients. The normal host mucosal immune defense inhibits pathogenic C. albicans through stepwise processes, such as pathogen recognition, cytokine production, and immune cell phagocytosis. Herein, the current advances in the interactions between C. albicans and host mucosal immune defenses have been summarized to improve understanding on the immune mechanisms against fungal infections.
Abusive Supervision and Creativity: Investigating the Moderating Role of Performance Improvement Attribution and the Mediating Role of Psychological Availability

The existing studies have indicated that abusive supervision affects creativity; however, the specific impact mechanism is still unclear due to the uncertain relationship between leadership and employee creativity. Based on the resource perspective, this study examines the influence of abusive supervision on creativity through psychological availability (PA) and the moderating of this mediation by performance improvement attribution (PIA). Based on a survey of 234 employees', the hypotheses have been tested and the results reveal that abusive supervision had a detrimental effect on employee creativity partially mediated by employee PA, and employees' PIA moderated the mediation. This study offers new insights into the mechanisms associated with the relationship between abusive supervision and creativity.
Neural Correlates of Attentional Modulation of Prepulse Inhibition

Prepulse inhibition (PPI) refers to the suppression of the startle reflex when the intense startling stimulus is shortly (20–500 ms) preceded by a weak non-startling stimulus (prepulse). Although the main neural correlates of PPI lie in the brainstem, previous research has revealed that PPI can be top-down modulated by attention. However, in the previous attend-to-prepulse PPI paradigm, only continuous prepulse but not discrete prepulse (20 ms) could elicit attentional modulation of PPI. Also, the relationship between the attentional enhancement of PPI and the changes in early cortical representations of prepulse signals is unclear. This study develops a novel attend-to-prepulse PPI task, when the discrete prepulse is set at 150 ms at a lead interval of 270 ms, and reveals that the PPI with attended prepulse is larger than the PPI with ignored prepulse. In addition, the early cortical representations (N1/P2 complex) of the prepulse show dissociation between the attended and ignored prepulse. N1 component is enhanced by directed attention, and the attentional increase of the N1 component is positively correlated with the attentional enhancement of PPI, whereas the P2 component is not affected by attentional modulation. Thus, directed attention to the prepulse can enhance both PPI and the early cortical representation of the prepulse signal (N1).
Neurofilament Light Chain as Biomarker for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two related currently incurable neurodegenerative diseases. ALS is characterized by degeneration of upper and lower motor neurons causing relentless paralysis of voluntary muscles, whereas in FTD, progressive atrophy of the frontal and temporal lobes of the brain results in deterioration of cognitive functions, language, personality, and behavior. In contrast to Alzheimer’s disease (AD), ALS and FTD still lack a specific neurochemical biomarker reflecting neuropathology ex vivo. However, in the past 10 years, considerable progress has been made in the characterization of neurofilament light chain (NFL) as cerebrospinal fluid (CSF) and blood biomarker for both diseases. NFL is a structural component of the axonal cytoskeleton and is released into the CSF as a consequence of axonal damage or degeneration, thus behaving in general as a relatively non-specific marker of neuroaxonal pathology. However, in ALS, the elevation of its CSF levels exceeds that observed in most other neurological diseases, making it useful for the discrimination from mimic conditions and potentially worthy of consideration for introduction into diagnostic criteria. Moreover, NFL correlates with disease progression rate and is negatively associated with survival, thus providing prognostic information. In FTD patients, CSF NFL is elevated compared with healthy individuals and, to a lesser extent, patients with other forms of dementia, but the latter difference is not sufficient to enable a satisfying diagnostic performance at individual patient level. However, also in FTD, CSF NFL correlates with several measures of disease severity. Due to technological progress, NFL can now be quantified also in peripheral blood, where it is present at much lower concentrations compared with CSF, thus allowing less invasive sampling, scalability, and longitudinal measurements. The latter has promoted innovative studies demonstrating longitudinal kinetics of NFL in presymptomatic individuals harboring gene mutations causing ALS and FTD. Especially in ALS, NFL levels are generally stable over time, which, together with their correlation with progression rate, makes NFL an ideal pharmacodynamic biomarker for therapeutic trials. In this review, we illustrate the significance of NFL as biomarker for ALS and FTD and discuss unsolved issues and potential for future developments.
Comparing the Impact of Heart Rate-Based In-Game Adaptations in an Exergame-Based Functional High-Intensity Interval Training on Training Intensity and Experience in Healthy Young Adults

Physical inactivity remains one of the biggest societal challenges of the 21st century. The gaming industry and the fitness sector have responded to this alarming fact with game-based or gamified training scenarios and thus established the promising trend of exergaming. Exergames—games played with the (whole) body as physical input—have been extolled as potential attractive and effective training tools. Simultaneously, researchers and designers are still exploring new approaches to exploit the full potential of this innovative and enjoyable training method. One way to boost the attractiveness and effectiveness of an exergame is to individualize it with game adaptations. A physiological parameter that is often used to balance the physical challenge and intensity of exergames to the player’s fitness skills is the heart rate (HR). Therefore, researchers and designers often rely on age-based, maximum HR (HRmax) formulas originating from performance diagnostics. In combination with the player’s assessed real-time HR during an exergame session, the pre-determined HRmax is used to adapt the game’s challenge to reach a pre-defined HR and physical intensity level (in-exergame adaptations), respectively. Although the validity and reliability of these age-based HRmax formulas were proven in heterogeneous target populations, their use is still often criticized as HR is an individual parameter that is affected by various internal and external factors. So far, no study has investigated whether the formula-based pre-calculated HRmax compared to a standardized individually pre-assessed HRmax elicits different training intensities, training experiences, and flow feelings in an exergame. Therefore, we compared both variants for in-exergame adaptation with the ExerCube – a functional high-intensity interval training exergame – in healthy young adults. Comparing the results of the two conditions, no significant differences were found for HR parameters and perceived physical and cognitive exertion, nor for overall flow feelings and physical activity enjoyment. Thus, the formula-based in-exergame adaptation approach was suitable in the presented study population, and the ExerCube provided an equally reliable in-exergame adaptation and comparable exergame play experiences. We discuss our findings in the context of related work on exergame adaptation approaches and draw out some implications for future adaptive exergame design and research topics.
Application of Machine Learning for Drug–Target Interaction Prediction

Exploring drug–target interactions by biomedical experiments requires a lot of human, financial, and material resources. To save time and cost to meet the needs of the present generation, machine learning methods have been introduced into the prediction of drug–target interactions. The large amount of available drug and target data in existing databases, the evolving and innovative computer technologies, and the inherent characteristics of various types of machine learning have made machine learning techniques the mainstream method for drug–target interaction prediction research. In this review, details of the specific applications of machine learning in drug–target interaction prediction are summarized, the characteristics of each algorithm are analyzed, and the issues that need to be further addressed and explored for future research are discussed. The aim of this review is to provide a sound basis for the construction of high-performance models.
Acidic Microenvironment Aggravates the Severity of Hepatic Ischemia/Reperfusion Injury by Modulating M1-Polarization Through Regulating PPAR-γ Signal

Hepatic injury induced by ischemia and reperfusion (HIRI) is a major clinical problem after liver resection or transplantation. The polarization of macrophages plays an important role in regulating the severity of hepatic ischemia/reperfusion injury. Recent evidence had indicated that the ischemia induces an acidic microenvironment by causing increased anaerobic glycolysis and accumulation of lactic acid. We hypothesize that the acidic microenvironment might cause the imbalance of intrahepatic immunity which aggravated HIRI. The hepatic ischemia/reperfusion injury model was established to investigate the effect of the acidic microenvironment to liver injury. Liposomes were used to deplete macrophages in vivo. Macrophages were cultured under low pH conditions to analyze the polarization of macrophages in vitro. Activation of the PPAR-γ signal was determined by Western blot. PPAR-γ agonist GW1929 was administrated to functionally test the role of PPAR-γ in regulating macrophage-mediated effects in the acidic microenvironment during HIRI. We demonstrate that acidic microenvironment aggravated HIRI while NaHCO3 reduced liver injury through neutralizing the acid, besides, liposome abolished the protective ability of NaHCO3 through depleting the macrophages. In vivo and vitro experiment showed that acidic microenvironment markedly promoted M1 polarization but inhibited M2 polarization of macrophage. Furthermore, the mechanistic study proved that the PPAR-γ signal was suppressed during the polarization of macrophages under pH = 6.5 culture media. The addition of PPAR-γ agonist GW1929 inhibited M1 polarization under acidic environment and reduced HIRI. Our results indicate that acidic microenvironment is a key regulator in HIRI which promoted M1 polarization of macrophages through regulating PPAR-γ. Conversely, PPAR-γ activation reduced liver injury, which provides a novel therapeutic concept to prevent HIRI.
The Role of BMP Signaling in Endothelial Heterogeneity

Bone morphogenetic proteins (BMPs), which compose the largest group of the transforming growth factor-β (TGF-ß) superfamily, have been implied to play a crucial role in diverse physiological processes. The most intriguing feature of BMP signaling is that it elicits heterogeneous responses from cells with equivalent identity, thus permitting highly context-dependent signaling outcomes. In endothelial cells (ECs), which are increasingly perceived as a highly heterogeneous population of cells with respect to their morphology, function, as well as molecular characteristics, BMP signaling has shown to elicit diverse and often opposite effects, illustrating the innate complexity of signaling responses. In this review, we provide a concise yet comprehensive overview of how outcomes of BMP signaling are modulated in a context-dependent manner with an emphasis on the underlying molecular mechanisms and summarize how these regulations of the BMP signaling promote endothelial heterogeneity.
Impairment and Compensation in Dexterous Upper-Limb Function After Stroke. From the Direct Consequences of Pyramidal Tract Lesions to Behavioral Involvement of Both Upper-Limbs in Daily Activities

Impairments in dexterous upper limb function are a significant cause of disability following stroke. While the physiological basis of movement deficits consequent to a lesion in the pyramidal tract is well demonstrated, specific mechanisms contributing to optimal recovery are less apparent. Various upper limb interventions (motor learning methods, neurostimulation techniques, robotics, virtual reality, and serious games) are associated with improvements in motor performance, but many patients continue to experience significant limitations with object handling in everyday activities. Exactly how we go about consolidating adaptive motor behaviors through the rehabilitation process thus remains a considerable challenge. An important part of this problem is the ability to successfully distinguish the extent to which a given gesture is determined by the neuromotor impairment and that which is determined by a compensatory mechanism. This question is particularly complicated in tasks involving manual dexterity where prehensile movements are contingent upon the task (individual digit movement, grasping, and manipulation…) and its objective (placing, two step actions…), as well as personal factors (motivation, acquired skills, and life habits…) and contextual cues related to the environment (presence of tools or assistive devices…). Presently, there remains a lack of integrative studies which differentiate processes related to structural changes associated with the neurological lesion and those related to behavioral change in response to situational constraints. In this text, we shall question the link between impairments, motor strategies and individual performance in object handling tasks. This scoping review will be based on clinical studies, and discussed in relation to more general findings about hand and upper limb function (manipulation of objects, tool use in daily life activity). We shall discuss how further quantitative studies on human manipulation in ecological contexts may provide greater insight into compensatory motor behavior in patients with a neurological impairment of dexterous upper-limb function.
Deciphering Network Crosstalk: The Current Status and Potential of miRNA Regulatory Networks on the HSP40 Molecular Chaperone Network

Molecular chaperone networks fulfill complex roles in protein homeostasis and are essential for maintaining cell health. Hsp40s (commonly referred to as J-proteins) have critical roles in development and are associated with a variety of human diseases, yet little is known regarding the J-proteins with respect to the post-transcriptional mechanisms that regulate their expression. With relatively small alterations in their abundance and stoichiometry altering their activity, post-transcriptional regulation potentially has significant impact on the functions of J-proteins. MicroRNAs (miRNAs) are a large group of non-coding RNAs that form a complex regulatory network impacting gene expression. Here we review and investigate the current knowledge and potential intersection of miRNA regulatory networks with the J-Protein chaperone network. Analysis of datasets from the current version of TargetScan revealed a great number of predicted microRNAs targeting J-proteins compared to the limited reports of interactions to date. There are likely unstudied regulatory interactions that influence chaperone biology contained within our analysis. We go on to present some criteria for prioritizing candidate interactions including potential cooperative targeting of J-Proteins by multiple miRNAs. In summary, we offer a view on the scope of regulation of J-Proteins through miRNAs with the aim of guiding future investigations by identifying key regulatory nodes within these two complex cellular networks.
Application of Diffusion Weighted Imaging Techniques for Differentiating Benign and Malignant Breast Lesions

To explore the value of apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM), and diffusional kurtosis imaging (DKI) based on diffusion weighted magnetic resonance imaging (DW-MRI) in differentiating benign and malignant breast lesions. A total of 215 patients with breast lesions were prospectively collected for breast MR examination. Single exponential, IVIM, and DKI models were calculated using a series of b values. Parameters including ADC, perfusion fraction (f), tissue diffusion coefficient (D), perfusion-related incoherent microcirculation (D*), average kurtosis (MK), and average diffusivity (MD) were compared between benign and malignant lesions. ROC curves were used to analyze the optimal diagnostic threshold of each parameter, and to evaluate the diagnostic efficacy of single and combined parameters. ADC, D, MK, and MD values were significantly different between benign and malignant breast lesions (P<0.001). Among the single parameters, ADC had the highest diagnostic efficiency (sensitivity 91.45%, specificity 82.54%, accuracy 88.84%, AUC 0.915) and the best diagnostic threshold (0.983 μm2/ms). The combination of ADC and MK offered high diagnostic performance (sensitivity 90.79%, specificity 85.71%, accuracy 89.30%, AUC 0.923), but no statistically significant difference in diagnostic performance as compared with single-parameter ADC (P=0.268). The ADC, D, MK, and MD parameters have high diagnostic value in differentiating benign and malignant breast lesions, and of these individual parameters the ADC has the best diagnostic performance. Therefore, our study revealed that the use of ADC alone should be useful for differentiating between benign and malignant breast lesions, whereas the combination of MK and ADC might improve the diagnostic performance to some extent.
Metabolic Disturbance and Th17/Treg Imbalance Are Associated With Progression of Gingivitis

Objective This study sought to explore the role of metabolic disturbance in immunoregulation of gingivitis targeting T helper 17 cells (Th17)/regulatory T cell (Treg). Materials and Methods A total of 20 gingivitis patients and 19 healthy volunteers were recruited. Quantitative real time polymerase chain reaction (qRT-PCR) was used to evaluate expression patterns of Forkhead box protein P3 (Foxp3), transforming growth factor-β (TGF-β), retinoid-related orphan receptor-gammat (RORγt) and interleukin 17A (IL-17A) in the peripheral blood lymphocytes of subjects across the two groups. Moreover, the enzyme-linked immunosorbent assay (ELISA) technique was used to detect levels of TGF-β, IL-4, IL-6,TL-10 and L-17A secreted in the plasma as well as the SIgA secreted in saliva. Flow cytometry was used to detect the percentage of CD4+CD25+ Foxp3+Treg cells and the percentage of CD4+IL-17A+ Th17 cells in whole blood of subjects in both groups. Gas chromatography-mass spectrometry (GC-MS) was employed to analyze the plasma metabolites in the gingivitis patient group. Statistical analysis was applied to determine whether the plasma metabolites and related metabolic pathways significantly differed between gingivitis patients and healthy controls. Ingenuity pathway analysis (IPA) was employed to identify the potential relation between the metabolites and the Th17 and Treg related pathway. Results The percentages of CD4+IL17A+Th17 cells and IL-17 significantly increased in the peripheral blood in the gingivitis group. Moreover, the upregulation of IL-17A mRNA and RORγt mRNA were also found in the gingivitis group. However, the percentage of CD4+CD25+ Foxp3+Treg cells and Foxp3 mRNA in the whole blood did not significantly change. However, TGF-β mRNA as well as TGF-β, IL-4, IL-6, IL-10 in the periperial blood and SIgA in the saliva were higher in the gingivitis group. Notably, that the ratio of Th17/Treg cells was significantly increased during peripheral circulation. Furthermore, we identified 18 different metabolites which were differentially expressed in plasma between the gingivitis and healthy control groups. Notably, the levels of cholesterol, glycerol 1-octadecanoate, d-glucose, uric acid, cyclohexaneacetic acid, 3-pyridine, tryptophan, and undecane 2,4-dimethyl were significantly up-regulated. whereas the levels of lactic acid, glycine, linoleic acid, monopalmitic acid, glycerol, palmitic acid, pyruvate, 1-(3-methylbutyl)-2,3,4,6-tetramethylbenzene, 1 5-anhydro d-altrol, and boric acid were down-regulated in the gingivitis group, relative to healthy controls. IPA showed that these metabolites are connected to IL17 signaling, TGF-B signaling, and IL10 signaling, which are related closely to Th17 and Treg pathway. Conclusion Overall, these results showed that disturbance to glycolysis as well as amino and fatty acid metabolism are associated with Th17/Treg balance in gingivitis. Impaired immunometabolism may influence some periodontally involved systemic diseases, hence it is a promising strategy in targeted development of treatment therapies.