Miracle-dz/UniFAR-FTUs huggingface dataset:
Critical Protein–Protein Interactions Determine the Biological Activity of Elk-1, a Master Regulator of Stimulus-Induced Gene Transcription

Elk-1 is a transcription factor that binds together with a dimer of the serum response factor (SRF) to the serum-response element (SRE), a genetic element that connects cellular stimulation with gene transcription. Elk-1 plays an important role in the regulation of cellular proliferation and apoptosis, thymocyte development, glucose homeostasis and brain function. The biological function of Elk-1 relies essentially on the interaction with other proteins. Elk-1 binds to SRF and generates a functional ternary complex that is required to activate SRE-mediated gene transcription. Elk-1 is kept in an inactive state under basal conditions via binding of a SUMO-histone deacetylase complex. Phosphorylation by extracellular signal-regulated protein kinase, c-Jun N-terminal protein kinase or p38 upregulates the transcriptional activity of Elk-1, mediated by binding to the mediator of RNA polymerase II transcription (Mediator) and the transcriptional coactivator p300. Strong and extended phosphorylation of Elk-1 attenuates Mediator and p300 recruitment and allows the binding of the mSin3A-histone deacetylase corepressor complex. The subsequent dephosphorylation of Elk-1, catalyzed by the protein phosphatase calcineurin, facilitates the re-SUMOylation of Elk-1, transforming Elk-1 back to a transcriptionally inactive state. Thus, numerous protein–protein interactions control the activation cycle of Elk-1 and are essential for its biological function.
Strength and Acid Resistance of Ceramic-Based Self-Compacting Alkali-Activated Concrete: Optimizing and Predicting Assessment

The development of self-compacting alkali-activated concrete (SCAAC) has become a hot topic in the scientific community; however, most of the existing literature focuses on the utilization of fly ash (FA), ground blast furnace slag (GBFS), silica fume (SF), and rice husk ash (RHA) as the binder. In this study, both the experimental and theoretical assessments using response surface methodology (RSM) were taken into account to optimize and predict the optimal content of ceramic waste powder (CWP) in GBFS-based self-compacting alkali-activated concrete, thus promoting the utilization of ceramic waste in construction engineering. Based on the suggested design array from the RSM model, experimental tests were first carried out to determine the optimum CWP content to achieve reasonable compressive, tensile, and flexural strengths in the SCAAC when exposed to ambient conditions, as well as to minimize its strength loss, weight loss, and UPVL upon exposure to acid attack. Based on the results, the optimum content of CWP that satisfied both the strength and durability aspects was 31%. In particular, a reasonable reduction in the compressive strength of 16% was recorded compared to that of the control specimen (without ceramic). Meanwhile, the compressive strength loss of SCAAC when exposed to acid attack minimized to 59.17%, which was lower than that of the control specimen (74.2%). Furthermore, the developed RSM models were found to be reliable and accurate, with minimum errors (RMSE < 1.337). In addition, a strong correlation (R > 0.99, R2 < 0.99, adj. R2 < 0.98) was observed between the predicted and actual data. Moreover, the significance of the models was also proven via ANOVA, in which p-values of less than 0.001 and high F-values were recorded for all equations.
Mycobacterium microti at the Environment and Wildlife Interface

An unexpected high presence of Mycobacterium microti in wild boar in Northern Italy (Garda Lake) has been reported since 2003, but the factors contributing to the maintenance of this pathogen are still unclear. In this study, we investigated the presence of M. microti in wild rodents and in water and soil samples collected at wild boar aggregation areas, such as watering holes, with the aim of clarifying their role in M. microti transmission. In total, 8 out of 120 captured animals tested positive for the Mycobacterium tuberculosis complex (MTBC) as assessed by real-time PCR, and six samples were confirmed to be M. microti. A strain with a genetic profile similar to those previously isolated in wild boars in the same area was isolated from one sample. Of the 20 water and 19 mud samples, 3 and 1, respectively, tested positive for the presence of MTBC, and spacer oligotype SB0118 (vole type) was detected in one sample. Our study suggests that wild rodents, in particular Apodemus sylvaticus, Microtus sp. and Apodemus flavicollis, play roles in the maintenance of M. microti infections in wild boar through ingestion or by contact with either infected excreta or a contaminated environment, such as at animal aggregation sites.
Disposable Food Packaging and Serving Materials—Trends and Biodegradability

Food is an integral part of everyone’s life. Disposable food serving utensils and tableware are a very convenient solution, especially when the possibility of the use of traditional dishes and cutlery is limited (e.g., takeaway meals). As a result, a whole range of products is available on the market: plates, trays, spoons, forks, knives, cups, straws, and more. Both the form of the product (adapted to the distribution and sales system) as well as its ecological aspect (biodegradability and life cycle) should be of interest to producers and consumers, especially considering the clearly growing trend of “eco-awareness”. This is particularly important in the case of single-use products. The aim of the study was to present the current trends regarding disposable utensils intended for contact with food in the context of their biodegradability. This paper has summarized not only conventional polymers but also their modern alternatives gaining the attention of manufacturers and consumers of single-use products (SUPs).
Effect of Psychobiotics on Psychometric Tests and Inflammatory Markers in Major Depressive Disorder: Meta-Analysis of Randomized Controlled Trials with Meta-Regression

Probiotics were shown to act positively on gut–brain axis signaling. We aimed to assess the effect of the administration of a new class of probiotics—psychobiotics—using data from individual psychometric scales, markers of the immune system and neuroactive metabolites. Medical databases were searched from database inception until 22 April 2021 for randomized clinical trials in clinically proven Major Depressive Disorder (MDD) patients treated with either probiotics or placebo reporting any psychometric score (PROSPERO registration number: CRD42021253024). Ten studies with 705 randomized participants and 603 analyzed were included. The mean age of individuals was 38.43 ± 12.1 years, predominantly women (n = 461, 76.45). The mean study duration was 48.8 ± 12.3 (range = 28–62) days. The dosage ranged between 1 × 109 to 2 × 1010 colony forming units (CFU)/day. We found that probiotics might alleviate symptoms of MDD; endpoint data (pooled scores): SMD = −0.292, 95%CI = −0.577 to −0.007, p < 0.044; change scores (BDI): SMD = −0.482, 95%CI = −0.854 to –0.109, p < 0.011; DM = −4.848, 95%CI = −8.559 to −1.137, p < 0.01. The therapy tended to be more effective with time of psychobiotic supplementation (coefficient = −0.12, SE = 0.06, Z = −1.84, p = 0.06) and in men (% of females: coefficient = 0.1, SE = 0.06, Z = 1.78, p = 0.07). Psychobiotics have great potential in the treatment of MDD. However, no specific strain/strains, dosage or duration of treatment can currently be recommended.
Magnetic Nanoparticles Used in Oncology

Recently, magnetic nanoparticles (MNPs) have more and more often been used in experimental studies on cancer treatments, which have become one of the biggest challenges in medical research. The main goal of this research is to treat and to cure advanced or metastatic cancer with minimal side effects through nanotechnology. Drug delivery approaches take into account the fact that MNPs can be bonded to chemotherapeutical drugs, nucleic acids, synthetized antibodies or radionuclide substances. MNPs can be guided, and different treatment therapies can be applied, under the influence of an external magnetic field. This paper reviews the main MNPs’ synthesis methods, functionalization with different materials and highlight the applications in cancer therapy. In this review, we describe cancer cell monitorization based on different types of magnetic nanoparticles, chemotherapy, immunotherapy, magnetic hyperthermia, gene therapy and ferroptosis. Examples of applied treatments on murine models or humans are analyzed, and glioblastoma cancer therapy is detailed in the review. MNPs have an important contribution to diagnostics, investigation, and therapy in the so called theranostics domain. The main conclusion of this paper is that MNPs are very useful in different cancer therapies, with limited side effects, and they can increase the life expectancy of patients with cancer drug resistance.
Short Alternative Route for Nuclear Fuel Reprocessing Based on Organic Phase Self-Splitting

A more sustainable management of natural resources and the establishment of processes allowing a joint management of nuclear materials to avoid their diversion from their civilian use are two issues for the nuclear industry. Short alternatives to existing processes have therefore been proposed based on known systems available, tributylphosphate (TBP), for the separation of actinides by liquid/liquid extraction. Proof of concept of such alternative has been established on the uranium(VI)/thorium(IV) system. From an organic phase consisting of a mixture of TBP/n-dodecane loaded with uranium and thorium, two fluxes have been obtained: the first contains almost all of the thorium in the presence of uranium in a controlled ratio, the second contains surplus uranium. Two levers were selected to control the spontaneous separation of the organic phase: the addition of concentrated nitric acid, or the temperature variation. Best results have been obtained using a temperature drop in the liquid/liquid extraction process, and variations in process conditions have been studied. Final metal recovery and solvent recycling have also been demonstrated, opening the door for further process development.
Serotonin after β-Adrenoreceptors’ Exposition: New Approaches for Personalized Data in Breast Cancer Cells

Serotonin is an important monoamine in the human body, playing crucial roles, such as a neurotransmitter in the central nervous system. Previously, our group reported that β-adrenergic drugs (ICI 118,551, isoprenaline, and propranolol) influence the proliferation of breast cancer cells (MCF-7 cells) and their inherent production of adrenaline. Thus, we aimed to investigate the production of serotonin in MCF-7 cells, clarifying if there is a relationship between this production and the viability of the cells. To address this question, briefly, we treated the MCF-7 cells with ICI 118,551, isoprenaline, and propranolol, and evaluated cellular viability and serotonin production by using MTT, Sulforhodamine B (SRB) and Neutral Red (NR) assays, and HPLC-ECD analysis, respectively. Our results demonstrate that isoprenaline promotes the most pronounced endogenous synthesis of serotonin, about 3.5-fold greater than control cells. Propranolol treatment also increased the synthesis of serotonin (when compared to control). On the other hand, treatment with the drug ICI 118,551 promoted a lower endogenous synthesis of serotonin, about 1.1-fold less than what was observed in the control. Together, these results reveal that MCF-7 cells can produce serotonin, and the drugs propranolol, isoprenaline and ICI 118,551 influence this endogenous production. For the first time, after modulation of the β-adrenergic system, a pronounced cellular growth can be related to higher consumption of serotonin by the cells, resulting in decreased levels of serotonin in cell media, indicative of the importance of serotonin in the growth of MCF-7 cells.
Navigating Nodal Metrics for Node-Positive Gastric Cancer in the United States: An NCDB-Based Study and Validation of AJCC Guidelines.

BACKGROUND The optimal number of examined lymph nodes (ELNs) and the positive lymph node ratio (LNR) for potentially curable gastric cancer are not established. We sought to determine clinical benchmarks for these values using a large national database. METHODS Demographic, clinicopathologic, and treatment-related data from patients treated using an R0, curative-intent gastrectomy registered in the National Cancer Database during 2004 to 2016 were evaluated. Patients with node-positive (pTxN+M0) disease were considered for analysis. RESULTS A total of 22,018 patients met the inclusion criteria, with a median follow-up of 2.2 years. Mean age at diagnosis was 65.6 years, 66% were male, 68% were White, 33% of tumors were located near the gastroesophageal junction, and 29% of patients had undergone preoperative therapy. Most primary tumors (62%) were category pT3-4, 67% had a poor or anaplastic grade, and 19% had signet features. Clinical nodal staging was inaccurate compared with staging at final pathology. The mean [SD] number of nodes examined was 19 [11]. On multivariable analysis, the pN category, ELNs, and LNR were independently associated with survival (all P<.0001). Using receiver operating characteristic (ROC) analysis, an optimal ELN threshold of ≥30 was established for patients with pN3b disease and was applied to the entire cohort. Node positivity and LNR had minimal change beyond 30 examined nodes. Stage-specific LNR thresholds calculated by ROC analysis were 11% for pN1, 28% for pN2, 58% for pN3a, 64% for pN3b, 30% for total combined. By using an ELN threshold of ≥30, prognostically advantageous stage-specific LNR values could be determined for 96% of evaluated patients. CONCLUSIONS Using a large national cancer registry, we determined that an ELN threshold of ≥30 allowed for prognostically advantageous LNRs to be achieved in 96% of patients. Therefore, ≥30 examined nodes should be considered a clinical benchmark for practice in the United States.
Gastroretentive Technologies in Tandem with Controlled-Release Strategies: A Potent Answer to Oral Drug Bioavailability and Patient Compliance Implications

There have been many efforts to improve oral drug bioavailability and therapeutic efficacy and patient compliance. A variety of controlled-release oral delivery systems have been developed to meet these needs. Gastroretentive drug delivery technologies have the potential to achieve retention of the dosage form in the upper gastrointestinal tract (GIT) that can be sufficient to ensure complete solubilisation of the drugs in the stomach fluids, followed by subsequent absorption in the stomach or proximal small intestine. This can be beneficial for drugs that have an “absorption window” or are absorbed to a different extent in various segments of the GIT. Therefore, gastroretentive technologies in tandem with controlled-release strategies could enhance both the therapeutic efficacy of many drugs and improve patient compliance through a reduction in dosing frequency. The paper reviews different gastroretentive drug delivery technologies and controlled-release strategies that can be combined and summarises examples of formulations currently in clinical development and commercially available gastroretentive controlled-release products. The different parameters that need to be considered and monitored during formulation development for these pharmaceutical applications are highlighted.
Protective Effects of Salicylic Acid and Calcium Chloride on Sage Plants (Salvia officinalis L. and Salvia elegans Vahl) under High-Temperature Stress

High-temperature stress is a major risk to fresh-market Salvia production, and heat intolerance is a major constraint in sage cultivation, particularly during the hot summer season. Previously, we investigated heat tolerance in five common-market cultivars of sage plants using leaf relative injury (RI) values and found that S. elegans Vahl (SE) and S. officinalis L. (SO) were the most and least heat-tolerant species, respectively. The exogenous applications of salicylic acid (SA) and calcium chloride (CaCl2) to alleviate heat stress in various species have been extensively studied, but reports of the effects of SA and CaCl2 treatments on the heat tolerance of sage plants are scarce. The objective of this study was to investigate how SA and CaCl2 affect the physiology and morphology of SE and SO plants under high-temperature conditions. Potted plants were pretreated with SA (0, 100, 200, 400, and 800 μM) and CaCl2 (0, 5, 10, and 15 mM), alone and combined, exposed to 55 °C and 80% humidity for 30 min, then placed in an environment-controlled chamber at 30 °C for three days and evaluated for changes in phenotypic appearance, RI, spectral reflectance, and chlorophyll fluorescence indices at different time intervals. Plants watered without chemical solutions were used as controls. Our results show that the growth of SO plants pretreated with SA and CaCl2 was more robust, compared with control plants, which were considerably affected by heat stress, resulting in brown, withered leaves and defoliation. The effects of the combined applications of SA (100 μM) and CaCl2 (5 mM) to SO plants were superior to control plants in increasing values of soil-plant analysis development (SPAD), normalized difference vegetation index (NDVI), and the maximal quantum yield of photosystemII photochemistry (Fv/Fm), while reducing RI%. Furthermore, SO plants exhibited higher SPAD and Fv/Fm values and lower RI% than SE plants in combined treatments at all time intervals after heat stress, implying that different genotypes displayed variations in their SPAD, Fv/Fm, and RI%. Thus, a combined treatment of 100 μM of SA and 5 mM of CaCl2 is effective and beneficial to plant appearance and ability to ameliorate heat stress. These indices can be used as indicators to characterize the physiology of these plants and applied on a commercial scale for informing the development of rapid and precise management practices on bedded sage plants grown in plant factories to achieve maximum market benefit.
Expression of Maf family proteins in glutamatergic neurons of the mouse olfactory bulb

The fate of neurons in the developing brain is largely determined by the combination of transcription factors they express. In particular, stem cells must follow different transcriptional cascades during differentiation in order to generate neurons with different neurotransmitter properties, such as glutamatergic and GABAergic neurons. In the mouse cerebral cortex, it has been shown that large Maf family proteins, MafA, MafB and c‐Maf, regulate the development of specific types of GABAergic interneurons but are not expressed in glutamatergic neurons. In this study, we examined the expression of large Maf family proteins in the developing mouse olfactory bulb (OB) by immunohistochemistry and found that the cell populations expressing MafA and MafB are almost identical, and most of them express Tbr2. As Tbr2 is expressed in glutamatergic neurons in the OB, we further examined the expression of glutamatergic and GABAergic neuronal markers in MafA and MafB positive cells. The results showed that in the OB, MafA and MafB are expressed exclusively in glutamatergic neurons, but not in GABAergic neurons. We also found that few cells express c‐Maf in the OB. These results indicate that, unlike the cerebral cortex, MafA and/or MafB may regulate the development of glutamatergic neurons in the developing OB. This study advances our knowledge about the development of glutamatergic neurons in the olfactory bulb, and also might suggest that mechanisms for the generation of projection neurons and interneurons differ between the cortex and the olfactory bulb, even though they both develop from the telencephalon.
Time-Restricted Feeding during Puberty Ameliorates Adiposity and Prevents Hepatic Steatosis in a Mouse Model of Childhood Obesity

Background: Time restricted feeding (TRF) refers to dietary interventions in which food access is limited during a specific timeframe of the day. TRFs have proven useful in improving metabolic health in adult subjects with obesity. Their beneficial effects are mediated, in part, through modulating the circadian rhythm. Nevertheless, the translation of these dietary interventions onto obese/overweight children and adolescents remains uncharacterized. The objective of this study is to explore the feasibility of temporal dietary interventions for improving metabolic health in the context of childhood obesity. Methods: We have previously developed a mouse model of early adiposity (i.e., childhood obesity) through litter size reduction. Mice raised in small litters (SL) became obese as early as by two weeks of age, and as adults, they developed several obesity-related co-morbidities, including insulin resistance, glucose intolerance and hepatic steatosis. Here, we explored whether two independent short-term chrono-nutritional interventions might improve metabolic health in 1-month-old pre-pubertal SL mice. Both TRFs comprised 8 h feeding/14 h fasting. In the first one (TRF1) Control and SL mice had access to the diet for 8 h during the dark phase. In the second intervention (TRF2) food was available during the light:dark transitions. Results: TRF1 did not alter food intake nor ameliorate adiposity in SL-TRF1. In contrast, SL-TRF2 mice showed unintentional reduction of caloric intake, which was accompanied by reduced total body weight and adiposity. Strikingly, hepatic triglyceride content was completely normalized in SL-TRF1 and SL-TRF2 mice, when compared to the ad lib-fed SL mice. These effects were partially mediated by (i) clock-dependent signals, which might modulate the expression of Pparg or Cpt1a, and (ii) clock-independent signals, such as fasting itself, which could influence Fasn expression. Conclusions: Time-restricted feeding is an effective and feasible nutritional intervention to improve metabolic health, namely hepatic steatosis, in a model of childhood obesity. These data open new avenues for future safe and efficient chrono-nutritional interventions aimed to improve metabolic health in children with overweight/obesity.
Dietary Administration of Novel Multistrain Probiotics from Healthy Grouper Intestines Promotes the Intestinal Immune Response against NNV Infection

Epinephelus lanceolatus (giant grouper) is a high-value cultured species in the Asia-Pacific region. However, nervous necrosis virus (NNV) is an infectious viral disease that affects over 120 species of marine cultured species and causes high mortality, ranging from 90–100% in the grouper industry. Probiotics isolated from the intestines of healthy individuals have provided insight into novel approaches involved in the defense against viral pathogens. In this study, we isolated three strains of bacteria as candidate probiotics from healthy grouper intestines and a 28-day feeding trial was performed. At day 21, the nervous necrosis virus (NNV) challenge test was conducted for 7 days to evaluate the antiviral effect of candidate probiotics. The results showed that candidate probiotics could improve growth conditions, such as weight gain (WG) and specific growth rate (SGR), and increase the utilization of feed. Furthermore, the candidate probiotic mixture had the ability to protect against NNV, which could decrease the mortality rate by 100% in giant grouper after NNV challenge. Subsequently, we analyzed the mechanism of the candidate probiotic mixture’s defense against NNV. A volcano plot revealed 203 (control vs. NNV), 126 (NNV vs. probiotics − NNV), and 5 (control vs. probiotics − NNV) differentially expressed transcripts in intestinal tissue. Moreover, principal components analysis (PCA) and cluster analysis heatmap showed large differences among the three groups. Functional pathway analysis showed that the candidate probiotic mixture could induce the innate and adaptive immunity of the host to defend against virus pathogens. Therefore, we hope that potential candidate probiotics could be successfully applied to the industry to achieve sustainable aquaculture.