Miracle-dz/UniFAR-FTUs huggingface dataset:
Magnoflorine Alleviates “M1” Polarized Macrophage-Induced Intervertebral Disc Degeneration Through Repressing the HMGB1/Myd88/NF-κB Pathway and NLRP3 Inflammasome

Intervertebral disc degeneration (IDD) is related to the deterioration of nucleus pulposus (NP) cells due to hypertrophic differentiation and calcification. The imbalance of pro-inflammatory (M1 type) and anti-inflammatory (M2 type) macrophages contributes to maintaining tissue integrity. Here, we aimed to probe the effect of Magnoflorine (MAG) on NP cell apoptosis mediated by “M1” polarized macrophages. THP-1 cells were treated with lipopolysaccharide (LPS) to induce “M1” polarized macrophages. Under the treatment with increasing concentrations of MAG, the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-18), high mobility group box protein 1 (HMGB1), as well as myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF-κB) and NOD-like receptor 3 (NLRP3) inflammasomes in THP-1 cells were determined. What’s more, human NP cells were treated with the conditioned medium (CM) from THP-1 cells. The NP cell viability and apoptosis were evaluated. Western blot (WB) was adopted to monitor the expression of apoptosis-related proteins (Bax, Caspase3, and Caspase9), catabolic enzymes (MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5), and extracellular matrix (ECM) compositions (collagen II and aggrecan) in NP cells. As a result, LPS evidently promoted the expression of pro-inflammatory cytokines and HMGB1, the MyD88-NF-κB activation, and the NLRP3 inflammasome profile in THP-1 cells, while MAG obviously inhibited the "M1″ polarization of THP-1 cells. After treatment with “M1” polarized THP-1 cell CM, NP cell viability was decreased, while cell apoptosis, the pro-inflammatory cytokines, apoptosis-related proteins, and catabolic enzymes were distinctly up-regulated, and ECM compositions were reduced. After treatment with MAG, NP cell damages were dramatically eased. Furthermore, MAG dampened the HMGB1 expression and inactivated the MyD88/NF-κB pathway and NLRP3 inflammasome in NP cells. In conclusion, this study confirmed that MAG alleviates “M1” polarized macrophage-mediated NP cell damage by inactivating the HMGB1-MyD88-NF-κB pathway and NLRP3 inflammasome, which provides a new reference for IDD treatment.
Having the Cake and Eating It Too: First-Order, Second-Order and Bifactor Representations of Work Engagement

Even though work engagement is a popular construct in organizational psychology, the question remains whether it is experienced as a global construct, or as its three components (vigor, dedication, absorption). The present study thus contributes to the ongoing scientific debate about the dimensionality of work engagement systematically compared one-factor, first-order, higher-order, and bifactor confirmatory factor analytic (CFA) representations of work engagement measured by the short version of Utrecht Work Engagement Scale (UWES-9). We also documented the validity evidence of the most optimal representation based on its test-criterion relationship with basic psychological need fulfillment at work, turnover intentions, work addiction, and work satisfaction. Based on responses provided by two distinct samples of employees (N1 = 242, N2 = 505), our results supported the superiority of the bifactor-CFA representation including a global factor of work engagement and three co-existing specific factors of vigor, dedication, and absorption. This representation replicated well across the two samples through tests of measurement invariance. Finally, while global work engagement was substantially related to all correlates, the specific factors also demonstrated meaningful associations over and above the global levels of work engagement.
Metformin Alleviates Hepatic Steatosis and Insulin Resistance in a Mouse Model of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Promoting Transcription Factor EB-Dependent Autophagy

Nonalcoholic fatty liver disease (NAFLD) results from an abnormal accumulation of lipids within hepatocytes, and is commonly associated with obesity, insulin resistance, and hyperlipidemia. Metformin is commonly used to treat type 2 diabetes mellitus and, in recent years, it was found to play a potential role in the amelioration of NAFLD. However, the mechanisms underlying the protective effect of metformin against NAFLD remain largely unknown. Transcription factor EB (TFEB) is a master transcriptional regulator of lysosomal biogenesis and autophagy and, when activated, is effective against disorders of lipid metabolism. However, the role of TFEB in hepatic steatosis is not well understood. In this report, we demonstrate that the activity of TFEB is reduced in the liver of mice fed a high-fat diet. Metformin treatment significantly reverses the activity of TFEB, and the protective effect of metformin against hepatic steatosis and insulin resistance is dependent on TFEB. We show that metformin-induced autophagy is regulated by TFEB, and our findings reveal that TFEB acts as a mediator, linking metformin with autophagy to reverse NAFLD, and highlight that TFEB may be a promising molecular target for the treatment of NAFLD.
The Response of Lentil (Lens culinaris Medik.) to Soil Moisture and Heat Stress Under Different Dates of Sowing and Foliar Application of Micronutrients

Soil moisture and air temperature stress are the two major abiotic factors limiting lentil (Lens culinaris Medik.) growth and productivity in the humid tropics. Field experiments were conducted during winter seasons (November to March) of 2018–2019 and 2019–2020 on clay loam soil (AericHaplaquept) of Eastern India to cultivate rainfed lentil, with residual moisture. The objective was to study the effect of different time of sowing and foliar spray of micronutrients in ameliorating the effect of heat and moisture stress lentil crop experience in its reproductive stage. The study was conducted with two different dates of sowing, November and December, as main plot treatment and micronutrients foliar spray of boron, iron, and zinc either alone or in combination as subplot treatment. No foliar spray treatment was considered as a control. The soil moisture content is depleted from 38 to 18% (sowing to harvest) during November sowing; however, in December sowing, the depletion is from 30 to 15%. The foliar spray of micronutrients helped to have a better canopy cover and thus reduced soil evaporation during the later stages of crop growth when the temperature was beyond the threshold temperature of the crop. Crop growth rate (CGR) and biomass were significantly higher (p ≤ 0.05) for November sown crop and with foliar spray of boron and iron (FSB + FE) micronutrients. In the later stages of the crop when the soil moisture started depleting with no precipitation, the canopy temperature increased compared with air temperature, leading to positive values of Stress Degree Days (SDD) index. Delay in sowing reduced the duration by 11.4 days (113.5 vs. 102.1 days), resulting in varied accumulated Growing Degree Days (GDD). FSB + FE resulted in the highest yield in both years (1,436 and 1,439 kg ha−1). The results of the study concluded that the optimum time of sowing and foliar spray of micronutrients may be helpful to alleviate the soil moisture and heat stress for the sustainability of lentil production in the subtropical region.
Neonatal Maternal Separation Modifies Proteostasis Marker Expression in the Adult Hippocampus

Exposure to early-life stress (ELS) can persistently modify neuronal circuits and functions, and contribute to the expression of misfolded and aggregated proteins that are hallmarks of several neurodegenerative diseases. The healthy brain is able to clear dysfunctional proteins through the ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP). Accumulating evidence indicates that impairment of these pathways contributes to enhanced protein aggregation and neurodegeneration. While stress is a known precipitant of neurological decline, few specific mechanistic links underlying this relationship have been identified. We hypothesized that neonatal maternal separation (MatSep), a well-established model of ELS, has the ability to alter the levels of UPS and ALP components in the brain, and thus has the potential to disrupt proteostasis. The expression of proteostasis-associated protein markers was evaluated by immunoblotting in the hippocampus and cortex of adult Wistar rats that were previously subjected to MatSep. We observed multiple sex- and MatSep-specific changes in the expression of proteins in the ALP, mitophagy, and UPS pathways, particularly in the hippocampus of adult animals. In contrast, MatSep had limited influence on proteostasis marker expression in the cortex of adult animals. Our results indicate that MatSep can selectively modify the intracellular protein degradation machinery in ways that may impact the development and progression of neurodegenerative disease.
Metformin Enhances B Cell Function and Antibody Responses of Elderly Individuals With Type-2 Diabetes Mellitus

Our previous work has shown that young and elderly patients with Type-2 Diabetes Mellitus (T2DM) treated with Metformin have optimal B cell function and serum antibodies specific for the seasonal influenza vaccine. In this paper, we have evaluated B cell function and the metabolic requirements of B cell antibody responses in elderly T2DM patients (ET2DM) taking or not Metformin, and compared to those of healthy elderly (EH) and healthy young (YH) individuals. Results show that Metformin significantly increases in vivo B cell function, measured by influenza vaccine-specific serum antibodies, in ET2DM patients to the levels observed in EH and more importantly in YH individuals. Metformin also decreases the frequencies of pro-inflammatory B cell subsets, as well as intrinsic inflammation and metabolic requirements of peripheral B cells from ET2DM. This hyper-metabolic phenotype of B cells from ET2DM is needed to support intrinsic inflammation, measured by the expression of transcripts for markers of the senescence-associated secretory phenotype (SASP), and the secretion of autoimmune antibodies. Importantly, B cell function in ET2DM patients taking Metformin is not only increased as compared to that in ET2DM patients not taking Metformin, but is comparable to B cell function measured in YH individuals. These results altogether strongly support the anti-aging effects of Metformin on humoral immunity.
Blood Plasma Biomarkers for Woody Breast Disease in Commercial Broilers

Woody breast (WB) myopathy results in poor muscle quality. The increasing incidence of WB over the last several years indicates a need for improved prediction or early diagnosis. We hypothesized that the use of body fluids, including blood, may be more suitable than breast muscle tissue in developing a minimally invasive diagnostic tool for WB detection. To identify potential early-age-biomarkers that may represent the potential onset of WB, blood samples were collected from 100, 4 wks old commercial male broilers. At 8 wks of age, WB conditions were scored by manual palpation. A total of 32 blood plasma samples (eight for each group of WB and non-WB control birds at two time points, 4 wks and 8 wks) were subjected to shotgun proteomics and untargeted metabolomics to identify differentially abundant plasma proteins and metabolites in WB broilers compared to non-WB control (Con) broilers. From the proteomics assay, 25 and 16 plasma proteins were differentially abundant (p < 0.05) in the 4 and 8 wks old samples, respectively, in WB compared with Con broilers. Of those, FRA10A associated CGG repeat 1 (FRAG10AC1) showed >2-fold higher abundance in WB compared with controls. In the 8 wks old broilers, 4 and 12 plasma proteins displayed higher and lower abundances, respectively, in WB compared with controls. Myosin heavy chain 9 (MYH9) and lipopolysaccharide binding protein (LBP) showed more than 2-fold higher abundances in WB compared with controls, while transferrin (TF) and complement C1s (C1S) showed more than 2-fold lower abundances compared with controls. From the untargeted metabolomics assay, 33 and 19 plasma metabolites were differentially abundant in birds at 4 and 8 wks of age, respectively, in WB compared with controls. In 4 wks old broilers, plasma 3-hydroxybutyric acid (3-HB) and raffinose concentrations showed the highest and lowest fold changes, respectively, in WB compared with controls. The blood plasma 3-HB and raffinose concentrations were confirmed with targeted biochemical assays. Blood biomarkers, such as 3-HB and raffinose, may be suitable candidate targets in the prediction of WB onset at early ages.
Deletion of the Wilms’ Tumor Suppressor Gene in the Cardiac Troponin-T Lineage Reveals Novel Functions of WT1 in Heart Development

Expression of Wilms’ tumor suppressor transcription factor (WT1) in the embryonic epicardium is essential for cardiac development, but its myocardial expression is little known. We have found that WT1 is expressed at low levels in 20–25% of the embryonic cardiomyocytes. Conditional ablation of WT1 using a cardiac troponin T driver (Tnnt2Cre) caused abnormal sinus venosus and atrium development, lack of pectinate muscles, thin ventricular myocardium and, in some cases, interventricular septum and cardiac wall defects, ventricular diverticula and aneurisms. Coronary development was normal and there was not embryonic lethality, although survival of adult mutant mice was reduced probably due to perinatal mortality. Adult mutant mice showed electrocardiographic anomalies, including increased RR and QRS intervals, and decreased PR intervals. RNASeq analysis identified differential expression of 137 genes in the E13.5 mutant heart as compared to controls. GO functional enrichment analysis suggested that both calcium ion regulation and modulation of potassium channels are deeply altered in the mutant myocardium. In summary, together with its essential function in the embryonic epicardium, myocardial WT1 expression is also required for normal cardiac development.
The Role of Coping Behavior in Healthcare Workers' Distress and Somatization During the COVID-19 Pandemic

Background: Constantly searching for a balance between work demands and their own physical and psychological health has challenged medical and nursing staff during the immediate wake of this COVID-19 viral epidemic leading to acute stress reactions and psychosomatic symptoms. Coping behavior might be a buffer for work-related stress in relation to mental well-being. The present study aims to evaluate the role of positive and negative stress-reducing activities on healthcare workers' mental and physical well-being. Methods: This was a cross-sectional study using an online survey that was sent out using our network of healthcare workers at the University of Antwerp and through social media. Socio-demographic data, coping behavior with the Palliative Pallet Scale (P3), and distress and somatization using the Four-dimensional symptom checklist were collected. Surveys were completed by 1,376 participants. Results: The results clearly showed that positive stress-reducing activities are related to fewer symptoms of distress and somatization. Providing direct care to COVID-19 patients was associated with a higher decrease of applying positive stress-reducing activities during the peak of the pandemic compared to the ideal situation. Finally, fewer symptoms of distress and somatization were associated with the following activities: reading, mind sports games, keeping a hobby collection, studying; engaging in sexual activities with your partner; cleaning the house, tidying up, working in the garden, doing household chores; exercising alone; walking, or taking a trip together with someone; exercise together with someone; watching TV, listening/playing (to) music/, playing computer games; playing a card game or other board game; and preparing something extra tasteful outside regular meals. Conclusion: Our study demonstrated an association between concrete coping behaviors and distress and somatization in healthcare workers during the first peak of the COVID-19 pandemic. The results provide relevant and additional insights to develop and investigate interventions among others in personal leadership and resilience.
Environmental Reconstruction and Tracking as Methods to Explore Social Interactions in Marine Environments: A Test Case With the Mediterranean Rainbow Wrasse Coris julis

A key aspect of understanding social interactions in marine animals is determining whether individuals freely interact in fission-fusion groups, or have spatially structured interactions, for example territories or home ranges. Territoriality can influence access to mates, food resources, or shelter sites, and may also impact conservation efforts, as the delineation of marine protected areas relies on knowledge of home ranges and movement patterns. However, accurately determining distribution and movement is challenging for many marine species, especially small and medium species, which cannot carry beacons or tags to automatically measure movement, and are also difficult for human observers to accurately follow. Yet these smaller species comprise the bulk of near-shore assemblages, and are essential conservation targets. As such, novel solutions for monitoring movement and behavior are required. Here we use a combination of tracking and environmental reconstruction to explore territoriality, aggression, and navigation in a small marine fish, explicitly applying this technique to questions of sociality in the marine environment. We use the Mediterranean Rainbow Wrasse, Coris julis, as a test case, but this approach can be extended to many other species and contexts. In contrast with previous reports for this species, we find that during our observation period, female C. julis occupy consistent territories over sand patches, and that they defend these territories against same-sex conspecifics. Displacement experiments revealed two further important social behavioral traits – first that displaced individuals were able to navigate back to their territory, avoiding almost all other female territories as they returned. Second that when displaced fish approached the territories of others, residents of these territories were often aggressive to the non-neighboring fish, in contrast with our observations of low aggression counts toward their natural neighbors. Resident fish therefore appear to show differing levels of aggressiveness depending on their social relationship with same-sex conspecifics. Overall, these results suggest a sophisticated degree of social behavior in this marine wrasse, dependent on social and structural environment, but which can only effectively be revealed by state-of-the-art tracking and environment reconstruction techniques.
Endothelial Activation in Orientia tsutsugamushi Infection Is Mediated by Cytokine Secretion From Infected Monocytes

Scrub typhus, caused by Orientia tsutsugamushi, is a common systemic infection in Asia. Delay in diagnosis and treatment can lead to vasculitis in the visceral organs and other complications. The mechanisms that drive endothelial activation and the inflammatory response in O. tsutsugamushi infection remain unknown. In addition, the interaction between monocytes and endothelial cells is still unclear. Here we demonstrate that O. tsutsugamushi-infected human dermal microvascular endothelial cells produced moderate levels of chemokines and low levels of IL-6 and IFN-β, but not TNF or IL-1β. Recombinant TNF and cytokine-rich supernatants from infected monocytes markedly enhanced chemokine production in infected endothelial cells. We also show that TNF and monocyte supernatants, but not O. tsutsugamushi infection of endothelial cells per se, upregulated the endothelial cell surface expression of ICAM-1, E-selectin, and tissue factor. This finding was consistent with the inability of O. tsutsugamushi to induce cytokine secretion from endothelial cells. The upregulation of surface molecules after stimulation with monocyte supernatants was significantly reduced by neutralizing anti-TNF antibodies. These results suggest that endothelial cell activation and response are mainly mediated by inflammatory cytokines secreted from monocytes.
A Root in Synapsis and the Other One in the Gut Microbiome-Brain Axis: Are the Two Poles of Ketogenic Diet Enough to Challenge Glioblastoma?

Glioblastoma is the most frequent and aggressive brain cancer in adults. While precision medicine in oncology has produced remarkable progress in several malignancies, treatment of glioblastoma has still limited available options and a dismal prognosis. After first-line treatment with surgery followed by radiochemotherapy based on the 2005 STUPP trial, no significant therapeutic advancements have been registered. While waiting that genomic characterization moves from a prognostic/predictive value into therapeutic applications, practical and easy-to-use approaches are eagerly awaited. Medical reports on the role of the ketogenic diet in adult neurological disorders and in glioblastoma suggest that nutritional interventions may condition outcomes and be associated with standard therapies. The acceptable macronutrient distribution of daily calories in a regular diet are 45–65% of daily calories from carbohydrates, 20–35% from fats, and 10–35% from protein. Basically, the ketogenic diet follows an approach based on low carbohydrates/high fat intake. In carbohydrates starvation, body energy derives from fat storage which is used to produce ketones and act as glucose surrogates. The ketogenic diet has several effects: metabolic interference with glucose and insulin and IGF-1 pathways, influence on neurotransmission, reduction of oxidative stress and inflammation, direct effect on gene expression through epigenetic mechanisms. Apart from these central effects working at the synapsis level, recent evidence also suggests a role for microbiome and gut-brain axis induced by a ketogenic diet. This review focuses on rationales supporting the ketogenic diet and clinical studies will be reported, looking at future possible perspectives.
Reusing Stadiums for a Greener Future: The Circular Design Potential of Football Architecture

Since the turn of the new Millennium, there has been an increase in efforts to build environmental-friendly sports arenas around the world. Fuelled by large sporting events like the 2000 Sydney Olympics, the ‘Green Games,’ and the 2006 FIFA World Cup in Germany, stadium architecture has become a vehicle for this trend. So far, the emphasis has primarily been on new arenas, in line with the widespread belief in international architecture of the 2000s that older buildings are less energy-efficient by default. In addition to that comes a conviction that newness is needed to attract sponsors, investors, and larger audiences—a position powered by commercial interest and the idea of the stadium as an ‘urban generator. ’ While new stadiums may have a significant potential when it comes to green performability, that does not necessarily mean that older stadiums are surplus to requirements, even from a climate perspective. In this paper, we look critically at the well-established strategy of replacing old stadiums with new ones by questioning the climate impact of new arenas and investigating the reuse potential of existing ones. We carry out in-depth analysis of two existing stadiums, Tynecastle Park in Edinburgh and Stadio Flaminio in Rome. One of them has already gone through renovation to remain in use while the other is vacant but currently under way to be renovated. We bring in fresh perspectives from sports science, preservation, architecture, and circular design theory to explain why older stadiums become obsolete and to challenge the premise of that destiny. The aim is not only to scrutinize the general lack of reuse but also to highlight green strategies which could give existing stadiums a longer life.