Miracle-dz/UniFAR-FTUs huggingface dataset:
Short-Term Diet Induced Changes in the Central and Circulating IGF Systems Are Sex Specific

Insulin-like growth factor (IGF) 1 exerts a wide range of functions in mammalians participating not only in the control of growth and metabolism, but also in other actions such as neuroprotection. Nutritional status modifies the IGF system, although little is known regarding how diet affects the newest members of this system including pregnancy-associated plasma protein-A (PAPP-A) and PAPP-A2, proteases that liberate IGF from the IGF-binding proteins (IGFBPs), and stanniocalcins (STCs) that inhibit PAPP-A and PAPP-A2 activity. Here we explored if a 1-week dietary change to either a high-fat diet (HFD) or a low-fat diet (LFD) modifies the central and peripheral IGF systems in both male and female Wistar rats. The circulating IGF system showed sex differences in most of its members at baseline. Males had higher levels of both free (p < 0.001) and total IGF1 (p < 0.001), as well as IGFBP3 (p < 0.001), IGFBP5 (p < 0.001), and insulin (p < 0.01). In contrast, females had higher serum levels of PAPP-A2 (p < 0.05) and IGFBP2 (p < 0.001). The responses to a short-term dietary change were both diet and sex specific. Circulating levels of IGF2 increased in response to LFD intake in females (p < 0.001) and decreased in response to HFD intake in males (p < 0.001). In females, LFD intake also decreased circulating IGFBP2 levels (p < 0.001). In the hypothalamus LFD intake increased IGF2 (p < 0.01) and IGFBP2 mRNA (p < 0.001) levels, as well as the expression of NPY (p < 0.001) and AgRP (p < 0.01), but only in males. In conclusion, short-term LFD intake induced more changes in the peripheral and central IGF system than did short-term HFD intake. Moreover, these changes were sex-specific, with IGF2 and IGFBP2 being more highly affected than the other members of the IGF system. One of the main differences between the commercial LFD employed and the HFD or normal rodent chow is that the LFD has a significantly higher sucrose content, suggesting that this nutrient could be involved in the observed responses.
The Inhibition Analysis of Two Heavy Metal ATPase Genes (NtHMA3a and NtHMA3b) in Nicotiana tabacum

ABSTRACT Previous studies suggested that plants detoxified mercury and cadmium through similar mechanisms. A heavy metal ATPase (adenosine triphosphatase) gene, HMA3, plays a key role in the plant's cadmium detoxification. To prove whether HMA3 also participates in mercury detoxification in plants, an experiment was designed to inhibit the expressions of HMA3 genes (NtHMA3a and NtHMA3b) in tobacco plants. Results showed that plants’ tolerance to mercury ions had not changed after the expressions of NtHMA3a and NtHMA3b were inhibited. When mercury content was measured from the whole seedlings, no differences had been observed among wild-type, NtHMA3a-NtHMA3b-RNAi, and the empty-vector transgenic plants. HMA3 was not the key gene responsible for plants’ mercury ion uptake from soil. Although the mercury content in the root was higher than that in the shoot for each seedling, in each treatment, neither in shoots nor in roots were statistical differences in mercury content found among NtHMA3a-NtHMA3b-RNAi, empty-vector transgenic, and wild-type plants. After the expressions of NtHMA3a and NtHMA3b were inhibited, the movement of mercury ions from root to shoot had not been affected. HMA3 was not the key gene responsible for mercury ion transportation from root to shoot. When mercury content was measured from the whole seedling, no significant difference had been found among wild-type, NtHMA3a-NtHMA3b-RNAi, and the empty-vector transgenic plants. For mercury ion translocation across tonoplast, the main pathway might not be HMA3, but ABC (ATP-binding cassette) transporters.
MiR-125a-3p-KLF15-BCAA Regulates the Skeletal Muscle Branched-Chain Amino Acid Metabolism in Nile Tilapia (Oreochromis niloticus) During Starvation

The branched-chain amino acids (BCAAs) play a key role in the energy metabolism of the muscle tissue and the Krüppel-like factor 15 (KLF15) as a transcription factor, which is a key regulator of BCAA metabolism in the skeletal muscle. This study assessed the effect of starvation for 0, 3, 7, and 15 days on BCAA metabolism in the skeletal muscle of Nile tilapia. The results showed that the expression of KLF15 showed a trend of increasing first and then decreasing during starvation, as well as the expression and activity of branched-chain aminotransferase 2 (BCAT2) and alanine aminotransferase (ALT). On the other hand, the content of BCAA was at first decreased and then upregulated, and it reached the lowest level after starvation for 3 days. In addition, through dual-luciferase reporter assay and injection experiments, it was found that KLF15 is the target gene of miR-125a-3p, which further verified that miR-125a-3p can regulate the BCAA metabolism by targeting KLF15 in the skeletal muscle. Thus, our work investigated the possible mechanisms of BCAA metabolism adapting to nutritional deficiency in the skeletal muscle of Nile tilapia and illustrated the regulation of BCAA metabolism through the miR-125a-3p-KLF15-BCAA pathway in the skeletal muscle.
Reciprocal Cooperation of Type A Procyanidin and Nitrofurantoin Against Multi-Drug Resistant (MDR) UPEC: A pH-Dependent Study

Uropathogenic Escherichia coli (UPEC) accounts for the majority of complicated and uncomplicated urinary tract infections. The use of phytomolecules in the treatment of UTI is fast gaining attention. The current report identifies a multidrug-resistant strain (QSLUPEC7), which is a strong biofilm producer, among the considered clinical isolates. The antimicrobial and antibiofilm activity was evaluated for the phytomolecule, Type A procyanidin (TAP) from Cinnamomum zeylanicum against QSLUPEC7. TAP treatment did not affect the growth of the MDR strain but affected the biofilm formation (~70% inhibition). The confocal microscopic examination reveals the biofilm inhibition and the live cells in the biofilm corroborates the antimicrobial results. Further, the synergy studies of TAP and nitrofurantoin (NIT) were carried out at different pH. TAP acts synergistically with nitrofurantoin at different pH considered. A closer look in the results reveals that at pH 5.8, maximum growth inhibition is recorded. The gene expression analysis shows that TAP alone and in combination with NIT downregulates the major fimbriae adhesins of UPEC. The results conclude that the TAP has an antibiofilm activity against the multidrug-resistant strain of UPEC, without affecting the growth. Also, TAP reciprocally cooperates with nitrofurantoin at different pH by downregulating the adhesins of UPEC.
Angiogenesis Inhibition by a Short 13 Amino Acid Peptide Sequence of Tetrastatin, the α4(IV) NC1 Domain of Collagen IV

Angiogenesis is defined as the formation of new capillaries by sprouting from the pre-existing microvasculature. It occurs in physiological and pathological processes particularly in tumor growth and metastasis. α1, α2, α3, and α6 NC1 domains from type IV collagen were reported to inhibit tumor angiogenesis. We previously demonstrated that the α4 NC1 domain from type IV collagen, named Tetrastatin, inhibited tumor growth in a mouse melanoma model. The inhibitory activity was located in a 13 amino acid sequence named QS-13. In the present paper, we demonstrate that QS-13 decreases VEGF-induced-angiogenesis in vivo using the Matrigel plug model. Fluorescence molecular tomography allows the measurement of a 65% decrease in Matrigel plug angiogenesis following QS-13 administration. The results are confirmed by CD31 microvessel density analysis on Matrigel plug slices. QS-13 peptide decreases Human Umbilical Vein Endothelial Cells (HUVEC) migration and pseudotube formation in vitro. Relevant QS-13 conformations were obtained from molecular dynamics simulations and docking. A putative interaction of QS-13 with α5β1 integrin was investigated. The interaction was confirmed by affinity chromatography, solid phase assay, and surface plasmon resonance. QS-13 binding site on α5β1 integrin is located in close vicinity to the RGD binding site, as demonstrated by competition assays. Collectively, our results suggest that QS-13 exhibits a mighty anti-angiogenic activity that could be used in cancer treatment and other pathologies with excessive angiogenesis such as hemangioma, psoriasis or diabetes.
Lasting and Sex-Dependent Impact of Maternal Immune Activation on Molecular Pathways of the Amygdala

The prolonged and sex-dependent impact of maternal immune activation (MIA) during gestation on the molecular pathways of the amygdala, a brain region that influences social, emotional, and other behaviors, is only partially understood. To address this gap, we investigated the effects of viral-elicited MIA during gestation on the amygdala transcriptome of pigs, a species of high molecular and developmental homology to humans. Gene expression levels were measured using RNA-Seq on the amygdala for 3-week-old female and male offspring from MIA and control groups. Among the 403 genes that exhibited significant MIA effect, a prevalence of differentially expressed genes annotated to the neuroactive ligand–receptor pathway, glutamatergic functions, neuropeptide systems, and cilium morphogenesis were uncovered. Genes in these categories included corticotropin-releasing hormone receptor 2, glutamate metabotropic receptor 4, glycoprotein hormones, alpha polypeptide, parathyroid hormone 1 receptor, vasointestinal peptide receptor 2, neurotensin, proenkephalin, and gastrin-releasing peptide. These categories and genes have been associated with the MIA-related human neurodevelopmental disorders, including schizophrenia and autism spectrum disorders. Gene network reconstruction highlighted differential vulnerability to MIA effects between sexes. Our results advance the understanding necessary for the development of multifactorial therapies targeting immune modulation and neurochemical dysfunction that can ameliorate the effects of MIA on offspring behavior later in life.
Bottom–Up Assessment Framework for Electrification Options in Energy-Intensive Process Industries

Electrification of industrial processes is one of the frequently discussed options to reduce greenhouse gas emissions from energy-intensive industries. This paper presents a bottom–up framework to assess process electrification options for energy-intensive industrial process plants in terms of greenhouse gas emissions and energy costs. The framework is based upon pinch analysis energy targetting methods, and accounts for site-specific conditions, including the effects on heat recovery potential and overall mass and energy balances. Furthermore, interactions between the process site and the background energy system are considered and scenarios are introduced in order to assess the impact of electrification options under different possible future energy market conditions. The framework is illustrated by a case study for an existing chemical plant for which there is a broad variety of electrification options that affect the process in different ways. The option of replacing the natural gas based syngas production unit with electrified syngas and steam production is analysed in detail. The results indicate natural gas savings of 173 MW whereas the electricity demand increases by 267 MW, leading to a strong increase in energy costs but also avoided greenhouse gas emissions of 333 kt/a. For two selected energy market scenarios for 2030 and 2040, the energy costs increase by 59 and 50 M€/a, respectively. The framework can be used to compare electrification with other process greenhouse gas emission reduction measures and to support policy and industrial decision making.
A Modified Procedure for Alcohol Determination by Dichromate Oxidation

The chemical oxidation method for alcohol determination in wine after microdistillation of the samples is used routinely in many winery laboratories. However, analysts often experience a number of difficulties with the procedure, including use of the distilling apparatus and indicator endpoint when dichromate is titrated with ferrous ammonium sulfate. The procedure was modified to avoid some of the problems. Five ml of wine were distilled in a Cash volatile acid still, operated to ensure complete condensation and recovery of alcohol distillate in a 50-ml volume. Two ml of distillate were oxidized at 60°C with 10 ml of dichromate solution (34 g potassium dichromate plus 325 ml sulfuric acid per liter). Alcohol concentration was determined spectrophotometrically at 600 nm, according to Caputi et al. [Am. J. Enol. Vitic. 19:160-5 (1968)]. The method as modified provided acceptable speed, precision, and accuracy for routine analysis of wine alcohol.
NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models of Apc Inactivation

Introduction Colorectal cancer (CRC) is the second leading cause of cancer death worldwide and most deaths result from metastases. We have analyzed animal models in which Apc, a gene that is frequently mutated during the early stages of colorectal carcinogenesis, was inactivated and human samples to try to identify novel potential biomarkers for CRC. Materials and Methods We initially compared the proteomic and transcriptomic profiles of the small intestinal epithelium of transgenic mice in which Apc and/or Myc had been inactivated. We then studied the mRNA and immunohistochemical expression of one protein that we identified to show altered expression following Apc inactivation, nucleosome assembly protein 1–like 1 (NAP1L1) in human CRC samples and performed a prognostic correlation between biomarker expression and survival in CRC patients. Results Nap1l1 mRNA expression was increased in mouse small intestine following Apc deletion in a Myc dependant manner and was also increased in human CRC samples. Immunohistochemical NAP1L1 expression was decreased in human CRC samples relative to matched adjacent normal colonic tissue. In a separate cohort of 75 CRC patients, we found a strong correlation between NAP1L1 nuclear expression and overall survival in those patients who had stage III and IV cancers. Conclusion NAP1L1 expression is increased in the mouse small intestine following Apc inactivation and its expression is also altered in human CRC. Immunohistochemical NAP1L1 nuclear expression correlated with overall survival in a cohort of CRC patients. Further studies are now required to clarify the role of this protein in CRC.
Human Follicle in vitro Culture Including Activation, Growth, and Maturation: A Review of Research Progress

Fertility preservation has received unprecedented attention nowadays. In addition to cryopreservation and re-implantation of embryos, oocytes, and ovarian tissue pieces, in vitro culture system for follicles/oocytes has been considered as an alternative strategy for fertility preservation. Since the metabolic dynamics and required nutrients are not entirely the same in different stages of follicular development, optimization of each culture step is needed. In this paper, literature regarding culture conditions in three steps were analyzed. Known additives in activation stage included 740Y-P, bpV(HOpic), follicle stimulating hormone (FSH), human serum albumin (HSA), ITS, growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), and cyclic adenosine monophosphate (cAMP), with different degrees of activation promotion and potential detrimental effect on DNA integrity. For isolated follicles growth stage, actin A, FSH, basic fibroblast growth factor (bFGF), estradiol were proved to improve development or proliferation. As for maturation, addition of growth hormone, melatonin, C-type natriuretic peptide (CNP), GDF9, cilostamide, or forskolin helped to regulate maturation rate or improve oocyte quality. Based on previous sequential culture system for human follicles, optimization is needed to achieve higher maturation rate and better oocyte quality, pursuant to current review, which demonstrated the effects of various additives on different stages.
Estimation of Trunk Muscle Forces Using a Bio-Inspired Control Strategy Implemented in a Neuro-Osteo-Ligamentous Finite Element Model of the Lumbar Spine

Low back pain (LBP), the leading cause of disability worldwide, remains one of the most common and challenging problems in occupational musculoskeletal disorders. The effective assessment of LBP injury risk, and the design of appropriate treatment modalities and rehabilitation protocols, require accurate estimation of the mechanical spinal loads during different activities. This study aimed to: (1) develop a novel 2D beam-column finite element control-based model of the lumbar spine and compare its predictions for muscle forces and spinal loads to those resulting from a geometrically matched equilibrium-based model; (2) test, using the foregoing control-based finite element model, the validity of the follower load (FL) concept suggested in the geometrically matched model; and (3) investigate the effect of change in the magnitude of the external load on trunk muscle activation patterns. A simple 2D continuous beam-column model of the human lumbar spine, incorporating five pairs of Hill’s muscle models, was developed in the frontal plane. Bio-inspired fuzzy neuro-controllers were used to maintain a laterally bent posture under five different external loading conditions. Muscle forces were assigned based on minimizing the kinematic error between target and actual postures, while imposing a penalty on muscular activation levels. As compared to the geometrically matched model, our control-based model predicted similar patterns for muscle forces, but at considerably lower values. Moreover, irrespective of the external loading conditions, a near (<3°) optimal FL on the spine was generated by the control-based predicted muscle forces. The variation of the muscle forces with the magnitude of the external load within the simulated range at the L1 level was found linear. This work presents a novel methodology, based on a bio-inspired control strategy, that can be used to estimate trunk muscle forces for various clinical and occupational applications toward shedding light on the ever-elusive LBP etiology.
An Analysis of Pumped Thermal Energy Storage With De-coupled Thermal Stores

Results from the first demonstration of Pumped Thermal Energy Storage (PTES) were published in 2019, indicating an achieved turn-round efficiency of 60–65% for a system capable of storing 600 kWh of electricity. PTES uses a theoretically reversible thermodynamic cycle involving compression and expansion stages with constant pressure heat addition and rejection to hot and cold thermal stores. Energy storage turn-round efficiency largely depends on the isentropic efficiencies of the compression and expansion equipment, the thermal effectiveness of the thermal stores, the presence of circuit pressure drops, heat leaks to and from the system and electrical machine efficiencies. We present a simulation model of a PTES system which is used to produce an inventory of the relative magnitudes of the various system losses. We consider the feasibility of a large-scale, 1 GWh nominal storage capacity, PTES system with de-coupled thermal stores; and provide comparison with the so far more investigated, coupled system. Based on ambitious yet realistic component performances, we calculate an energy storage turn around efficiency of 65.3 and 59.5% for the coupled and de-coupled systems, respectively. Even with dwell times in the charged state as long as 5 days, a turn-round efficiency of over 50% is still predicted in both systems; suggesting that PTES could offer a viable large-scale, long duration energy store.
A Novel Immune-Related Competing Endogenous RNA Network Predicts Prognosis of Acute Myeloid Leukemia

Background Acute myeloid leukemia (AML) is a genetically, biologically and clinically heterogeneous hematopoietic malignancy that is highly dependent on the bone marrow (BM) microenvironment. Infiltrated immune cells and stromal cells are an important part of the BM microenvironment and significantly affect the progression of AML. Recently, the competing endogenous RNA hypothesis has gained great interests in the study of molecular and biological mechanisms of tumor occurrence and progression. However, research on how competing endogenous RNA relates to leukemia tumor microenvironment remains uninvestigated. Methods In this study, mRNA, miRNA and lncRNA data and clinical information of the AML cohort were obtained from The Cancer Genome Atlas (TCGA) database, and the immune and stromal scores were calculated using the ESTIMATE algorithm. Results We found that immune scores were significantly correlated with cytogenetic risk and overall survival, and also identified microenvironment-related mRNAs, miRNAs, and lncRNAs based on the immune and stromal scores. Differentially expressed mRNAs and lncRNAs were applied to weighted correlation network analysis (WGCNA) to identify the modules most relevant to the immune microenvironment of AML. Using miRNA database to predict miRNA-targeted genes, we established the immune-related competing endogenous RNA network consisting of 33 lncRNAs, 21 miRNAs and 135 mRNAs. Prognostic analysis was performed on the genes in the immune-related competing endogenous RNA network to screen out 15 lncRNAs, 2 miRNAs and 31 mRNAs with prognostic values. Conclusion In summary, we identified a novel immune-related mRNA-miRNA-lncRNA competing endogenous RNA network associated with the prognosis of AML, which may contribute to better understanding of the development and progression of AML and to serve as novel therapeutic targets.
Genome-Wide Transcriptional Regulation of the Long Non-coding RNA Steroid Receptor RNA Activator in Human Erythroblasts

Erythropoiesis of human hematopoietic stem cells (HSCs) maintains generation of red blood cells throughout life. However, little is known how human erythropoiesis is regulated by long non-coding RNAs (lncRNAs). By using ChIRP-seq, we report here that the lncRNA steroid receptor RNA activator (SRA) occupies chromatin, and co-localizes with CTCF, H3K4me3, and H3K27me3 genome-wide in human erythroblast cell line K562. CTCF binding sites that are also occupied by SRA are enriched for either H3K4me3 or H3K27me3. Transcriptome-wide analyses reveal that SRA facilitates expression of erythroid-associated genes, while repressing leukocyte-associated genes in both K562 and CD36-positive primary human proerythroblasts derived from HSCs. We find that SRA-regulated genes are enriched by both CTCF and SRA bindings. Further, silencing of SRA decreases expression of the erythroid-specific markers TFRC and GYPA, and down-regulates expression of globin genes in both K562 and human proerythroblast cells. Taken together, our findings establish that the lncRNA SRA occupies chromatin, and promotes transcription of erythroid genes, therefore facilitating human erythroid transcriptional program.