Miracle-dz/UniFAR-FTUs huggingface dataset:
Histological Effects of Excessive Consumption of Zingeber officinale on Liver and Spleen of the Mice

Ginger (Zingeber officinale) is a natural dietary component with antioxidant and antiinflammation. In the present study, the influence of ginger ethanol extract on liver and spleen of mice was investigated. The animals were divided in to four groups then treated with different concentrations of ginger extract (0, 50, 75, 100 mg/ kg) for 10 days, and then the animals scarified to evaluate histological change on liver and spleen. Results showed that liver section of mice treated with (50 mg/kg) of extract exhibited no clear pathological lesion with the presence of moderate of kuppfer cell. While the sectional liver treated with (75 mg/kg) of extract showed double nuclei and proliferation of cells. Aggregation of mononuclear cells mainly macrophage and lymphocyte in liver parenchyma was observed in liver section of mice treated with (100 mg/kg) of extract. Spleen section of mice treated with (50 mg/kg) of extract showed hyperplasia of red pulp with proliferation with mononuclear cell around sinusoid form cord like structure. While, the sectional spleen treated with (75 mg/kg) of extract showed moderate hyperplasia of white pulp. Moderate peri-arterial hyper plasma and aggregate of lymphocyte and mononuclear cells in red pulp was notes in spleen section of mice treated with (100mg/kg) of extract.
Design and Encapsulation of Immunomodulators onto Gold Nanoparticles in Cancer Immunotherapy

The aim of cancer immunotherapy is to reactivate autoimmune responses to combat cancer cells. To stimulate the immune system, immunomodulators, such as adjuvants, cytokines, vaccines, and checkpoint inhibitors, are extensively designed and studied. Immunomodulators have several drawbacks, such as drug instability, limited half-life, rapid drug clearance, and uncontrolled immune responses when used directly in cancer immunotherapy. Several strategies have been used to overcome these limitations. A simple and effective approach is the loading of immunomodulators onto gold-based nanoparticles (GNPs). As gold is highly biocompatible, GNPs can be administered intravenously, which aids in increasing cancer cell permeability and retention time. Various gold nanoplatforms, including nanospheres, nanoshells, nanorods, nanocages, and nanostars have been effectively used in cancer immunotherapy. Gold nanostars (GNS) are one of the most promising GNP platforms because of their unusual star-shaped geometry, which significantly increases light absorption and provides high photon-to-heat conversion efficiency due to the plasmonic effect. As a result, GNPs are a useful vehicle for delivering antigens and adjuvants that support the immune system in killing tumor cells by facilitating or activating cytotoxic T lymphocytes. This review represents recent progress in encapsulating immunomodulators into GNPs for utility in a cancer immunotherapeutic regimen.
Analysis of Spatial and Temporal Distribution of Purinergic P2 Receptors in the Mouse Hippocampus

ATP and other nucleotides are important glio-/neurotransmitters in the central nervous system. They bind to purinergic P2X and P2Y receptors that are ubiquitously expressed in various brain regions modulating various physiological and pathophysiological processes. P2X receptors are ligand-gated ion channels mediating excitatory postsynaptic responses whereas P2Y receptors are G protein-coupled receptors mediating slow synaptic transmission. A variety of P2X and P2Y subtypes with distinct neuroanatomical localization provide the basis for a high diversity in their function. There is increasing evidence that P2 receptor signaling plays a prominent role in learning and memory and thus, in hippocampal neuronal plasticity. Learning and memory are time-of-day-dependent. Moreover, extracellular ATP shows a diurnal rhythm in rodents. However, it is not known whether P2 receptors have a temporal variation in the hippocampus. This study provides a detailed systematic analysis on spatial and temporal distribution of P2 in the mouse hippocampus. We found distinct spatial and temporal distribution patterns of the P2 receptors in different hippocampal layers. The temporal distribution of P2 receptors can be segregated into two large time domains, the early to mid-day and the mid to late night. This study provides an important basis for understanding dynamic P2 purinergic signaling in the hippocampal glia/neuronal network.
Model-based data analysis of tissue growth in thin 3D printed scaffolds

Tissue growth in three-dimensional (3D) printed scaffolds enables exploration and control of cell behaviour in biologically realistic geometries. Cell proliferation and migration in these experiments have yet to be explicitly characterised, limiting the ability of experimentalists to determine the effects of various experimental conditions, such as scaffold geometry, on cell behaviour. We consider tissue growth by osteoblastic cells in melt electro-written scaffolds that comprise thin square pores with sizes that we deliberately vary. We collect highly detailed temporal measurements of the average cell density, tissue coverage, and tissue geometry. To quantify tissue growth in terms of the underlying cell proliferation and migration processes, we introduce and calibrate a mechanistic mathematical model based on the Porous-Fisher reaction-diffusion equation. Parameter estimates and uncertainty quantification through profile likelihood analysis reveal consistency in the rate of cell proliferation and steady-state cell density between pore sizes. This analysis also serves as an important model verification tool: while the use of reaction-diffusion models in biology is widespread, the appropriateness of these models to describe tissue growth in 3D scaffolds has yet to be explored. We find that the Porous-Fisher model is able to capture features relating to the cell density and tissue coverage, but is not able to capture geometric features relating to the circularity of the tissue interface. Our analysis identifies two distinct stages of tissue growth, suggests several areas for model refinement, and provides guidance for future experimental work that explores tissue growth in 3D printed scaffolds. Author Summary Advances in 3D printing technology have led to cell culture experiments that realistically capture natural biological environments. Despite the necessity of quantifying cell behaviour with parameters that can be compared between experiments, many existing mathematical models of tissue growth in these experiments neglect information relating to population size. We consider tissue growth by cells on 3D printed scaffolds that comprise square pores of various sizes in this work. We apply a relatively simple mathematical model based on the Porous-Fisher reaction-diffusion equation to interpret highly detailed measurements relating to both the cell density and the quantity of tissue deposited. We analyse the efficacy of such a model in capturing cell behaviour seen in the experiments and quantify cell behaviour in terms of parameters that carry a biologically meaningful interpretation. Our analysis identifies important areas for model refinement and provides guidance for future data-collection and experimentation that explores tissue growth in 3D printed scaffolds.
Plasma-Induced Catalyst Support Defects for the Photothermal Methanation of Carbon Dioxide

The presence of defects in a catalyst support is known to benefit catalytic activity. In this work, a He-plasma treatment-based strategy for introducing and stabilising defects on a Ni/TiO2 catalyst for photothermal CO2 hydrogenation was established. The impact of pretreatment step sequence—which comprised He-plasma treatment and reduction/passivation—on defect generation and stabilisation within the support was evaluated. Characterisation of the Ni/TiO2 catalysts indicated that defects created in the TiO2 support during the initial plasma treatment stage were then stabilised by the reduction/passivation process, (P-R)Ni/TiO2. Conversely, performing reduction/passivation first, (R-P)Ni/TiO2, invoked a resistance to subsequent defect formation upon plasma treatment and consequently, poorer photothermal catalytic activity. The plasma treatment altered the metal-support interaction and ease of catalyst reduction. Under photothermal conditions, (P-R)Ni/TiO2 reached the highest methane production in 75 min, while (R-P)Ni/TiO2 required 165 min. Decoupling the impacts of light and heat indicated thermal dominance of the reaction with CO2 conversion observed from 200 °C onwards. Methane was the primary product with carbon monoxide detected at 350 °C (~2%) and 400 °C (~5%). Overall, the findings demonstrate the importance of pretreatment step sequence when utilising plasma treatment to generate active defect sites in a catalyst support.
New specimens provide insights into the anatomy of the dinosauriform Lewisuchus admixtus Romer, 1972 from the upper Triassic levels of the Chañares Formation, NW Argentina

Lewisuchus admixtus is an early dinosauriform described by Alfred Romer in 1972 on the basis of a single, incomplete skeleton, collected in lower Upper Triassic rocks of the renowned Chañares Formation, at the Los Chañares type‐locality, La Rioja Province, north‐western Argentina. Recent field explorations to the type‐locality resulted in the discovery of two partial articulated skeletons, which provide significant novel information. The cranial bones, presacral series, femur, tibia, and proximal tarsals of the new specimens match the preserved overlapping anatomy of the holotype and previously referred specimens of L. admixtus, including the presence of unique combination of character states among dinosauriforms (anterior presacral column with additional ossification on the top of neural spines, dorsal neural spines fan‐shaped, anterior surface of the astragalus with a dorsally curved groove, and an inflated area on the anterior portion of the medial surface of this bone). This new information improves our understanding of the anatomy and taxonomy of early dinosauriforms and reinforces the role of Argentinean beds on the study of the origin of dinosaurs.
The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known transcription factor best recognised as one of the main regulators of the oxidative stress response. Beyond playing a crucial role in cell defence by transactivating cytoprotective genes encoding antioxidant and detoxifying enzymes, Nrf2 is also implicated in a wide network regulating anti-inflammatory response and metabolic reprogramming. Such a broad spectrum of actions renders the factor a key regulator of cell fate and a strategic player in the control of cell transformation and response to viral infections. The Nrf2 protective roles in normal cells account for its anti-tumour and anti-viral functions. However, Nrf2 overstimulation often occurs in tumour cells and a complex correlation of Nrf2 with cancer initiation and progression has been widely described. Therefore, if on one hand, Nrf2 has a dual role in cancer, on the other hand, the factor seems to display a univocal function in preventing inflammation and cytokine storm that occur under viral infections, specifically in coronavirus disease 19 (COVID-19). In such a variegate context, the present review aims to dissect the roles of Nrf2 in both cancer and COVID-19, two widespread diseases that represent a cause of major concern today. In particular, the review describes the molecular aspects of Nrf2 signalling in both pathological situations and the most recent findings about the advantages of Nrf2 inhibition or activation as possible strategies for cancer and COVID-19 treatment respectively.
mTOR Activity and Autophagy in Senescent Cells, a Complex Partnership

Cellular senescence is a form of proliferative arrest triggered in response to a wide variety of stimuli and characterized by unique changes in cell morphology and function. Although unable to divide, senescent cells remain metabolically active and acquire the ability to produce and secrete bioactive molecules, some of which have recognized pro-inflammatory and/or pro-tumorigenic actions. As expected, this “senescence-associated secretory phenotype (SASP)” accounts for most of the non-cell-autonomous effects of senescent cells, which can be beneficial or detrimental for tissue homeostasis, depending on the context. It is now evident that many features linked to cellular senescence, including the SASP, reflect complex changes in the activities of mTOR and other metabolic pathways. Indeed, the available evidence indicates that mTOR-dependent signaling is required for the maintenance or implementation of different aspects of cellular senescence. Thus, depending on the cell type and biological context, inhibiting mTOR in cells undergoing senescence can reverse senescence, induce quiescence or cell death, or exacerbate some features of senescent cells while inhibiting others. Interestingly, autophagy—a highly regulated catabolic process—is also commonly upregulated in senescent cells. As mTOR activation leads to repression of autophagy in non-senescent cells (mTOR as an upstream regulator of autophagy), the upregulation of autophagy observed in senescent cells must take place in an mTOR-independent manner. Notably, there is evidence that autophagy provides free amino acids that feed the mTOR complex 1 (mTORC1), which in turn is required to initiate the synthesis of SASP components. Therefore, mTOR activation can follow the induction of autophagy in senescent cells (mTOR as a downstream effector of autophagy). These functional connections suggest the existence of autophagy regulatory pathways in senescent cells that differ from those activated in non-senescence contexts. We envision that untangling these functional connections will be key for the generation of combinatorial anti-cancer therapies involving pro-senescence drugs, mTOR inhibitors, and/or autophagy inhibitors.
Mouse Models of Achromatopsia in Addressing Temporal “Point of No Return” in Gene-Therapy

Achromatopsia is characterized by amblyopia, photophobia, nystagmus, and color blindness. Previous animal models of achromatopsia have shown promising results using gene augmentation to restore cone function. However, the optimal therapeutic window to elicit recovery remains unknown. Here, we attempted two rounds of gene augmentation to generate recoverable mouse models of achromatopsia including a Cnga3 model with a knock-in stop cassette in intron 5 using Easi-CRISPR (Efficient additions with ssDNA inserts-CRISPR) and targeted embryonic stem (ES) cells. This model demonstrated that only 20% of CNGA3 levels in homozygotes derived from target ES cells remained, as compared to normal CNGA3 levels. Despite the low percentage of remaining protein, the knock-in mouse model continued to generate normal cone phototransduction. Our results showed that a small amount of normal CNGA3 protein is sufficient to form “functional” CNG channels and achieve physiological demand for proper cone phototransduction. Thus, it can be concluded that mutating the Cnga3 locus to disrupt the functional tetrameric CNG channels may ultimately require more potent STOP cassettes to generate a reversible achromatopsia mouse model. Our data also possess implications for future CNGA3-associated achromatopsia clinical trials, whereby restoration of only 20% functional CNGA3 protein may be sufficient to form functional CNG channels and thus rescue cone response.
Cell Membrane-Coated Halloysite Nanotubes for Target-Specific Nanocarrier for Cancer Phototherapy

Naturally-occurring halloysite nanotubes (HNTs) have many advantages for constructing target-specific delivery of phototherapeutic agents. Here, HNTs were labeled with fluorescein isothiocyanate (FITC) and loaded with the type-II photosensitizer indocyanine green (ICG) for phototherapy. HNTs-FITC-ICG was structurally stable due to presence of HNTs as the nanocarrier and protective agent. The nanocarrier was further wrapped with red blood cell membrane (RBCM) to enhance the biocompatibility. The HNTs-FITC-ICG-RBCM nanocarrier show high cytocompatibility and hemocompatibility. Due to the photothermal effect of ICG, a significant temperature rising was achieved by irradiation of the nanocarrier using 808 nm laser. The photothermal temperature rising was used to kill the cancer cells effectively. The HNTs-FITC-ICG-RBCM nanocarrier was further linked with anti-EpCAM to endow it with targeting therapy performance against breast cancer, and the anti-EpCAM-conjugated nanocarrier exhibited significantly tumor-specific accumulation. The RBCM-coated and biocompatible HNTs nanocarrier is a promising candidate for target-specific therapy of cancer.
The 3,4-Quinones of Estrone and Estradiol Are the Initiators of Cancer whereas Resveratrol and N-acetylcysteine Are the Preventers

This article reviews evidence suggesting that a common mechanism of initiation leads to the development of many prevalent types of cancer. Endogenous estrogens, in the form of catechol estrogen-3,4-quinones, play a central role in this pathway of cancer initiation. The catechol estrogen-3,4-quinones react with specific purine bases in DNA to form depurinating estrogen-DNA adducts that generate apurinic sites. The apurinic sites can then lead to cancer-causing mutations. The process of cancer initiation has been demonstrated using results from test tube reactions, cultured mammalian cells, and human subjects. Increased amounts of estrogen-DNA adducts are found not only in people with several different types of cancer but also in women at high risk for breast cancer, indicating that the formation of adducts is on the pathway to cancer initiation. Two compounds, resveratrol, and N-acetylcysteine, are particularly good at preventing the formation of estrogen-DNA adducts in humans and are, thus, potential cancer-prevention compounds.
Effects of Antidepressant Treatment on Neurotrophic Factors (BDNF and IGF-1) in Patients with Major Depressive Disorder (MDD)

Major depressive disorder (MDD) remains the subject of ongoing research as a multifactorial disease and a serious public health problem. There is a growing body of literature focusing on the role of neurotrophic factors in pathophysiology of MDD. A neurotrophic hypothesis of depression proposes that abnormalities of neurotrophins serum levels lead to neuronal atrophy and decreased neurogenesis, resulting in mood disorders. Consequently, in accordance with recent findings, antidepressant treatment modifies the serum levels of neurotrophins and thus leads to a clinical improvement of MDD. The purpose of this review is to summarize the available data on the effects of various antidepressants on serum levels of neurotrophins such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF-1). In addition, the authors discuss their role as prognostic factors for treatment response in MDD. A literature search was performed using the PubMed database. Following the inclusion and exclusion criteria, nine original articles and three meta-analyses were selected. The vast majority of studies have confirmed the effect of antidepressants on BDNF levels. Research on IGF-1 is limited and insufficient to describe the correlation between different antidepressant drugs and factor serum levels; however, four studies indicated a decrease in IGF-1 after treatment. Preliminary data suggest BDNF as a promising predictor of treatment response in MDD patients. The role of IGF-1 needs further investigation.
S100A9 Alters the Pathway of Alpha-Synuclein Amyloid Aggregation

The formation of amyloid fibril plaques in the brain creates inflammation and neuron death. This process is observed in neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. Alpha-synuclein is the main protein found in neuronal inclusions of patients who have suffered from Parkinson’s disease. S100A9 is a calcium-binding, pro-inflammation protein, which is also found in such amyloid plaques. To understand the influence of S100A9 on the aggregation of α-synuclein, we analyzed their co-aggregation kinetics and the resulting amyloid fibril structure by Fourier-transform infrared spectroscopy and atomic force microscopy. We found that the presence of S100A9 alters the aggregation kinetics of α-synuclein and stabilizes the formation of a particular amyloid fibril structure. We also show that the solution’s ionic strength influences the interplay between S100A9 and α-synuclein, stabilizing a different structure of α-synuclein fibrils.
Mediation of perceived stress and cortisol in the association between neuroticism and global cognition in older adults:a longitudinal study.

Neuroticism has been associated with a greater dementia risk, but its association with cognitive decline in healthy older adults remains unclear. Stress has been proposed as one of the mechanisms that could explain this relationship. Our aim was to analyze, in healthy older people, the mediating role of perceived stress and the Hypothalamic-Pituitary-Adrenal (HPA) axis in the association between neuroticism and global cognition. At Wave 1 and 2 (four-year follow-up), 87 older people (49.4% women; M age = 65.08, SD= 4.54 at Wave 1) completed a neuropsychological battery and the Perceived Stress Scale (PSS), and provided saliva samples on two [Wave 1] and three [Wave 2] consecutive days to measure the wake-to-bed slope. In Wave 2, neuroticism was assessed with the NEO- Five-Factor Inventory. PSS, but not the wake-to-bed slope, mediated the negative associations between neuroticism and global cognition (Waves 1, 2, and change). Regarding gender differences, PSS (Waves 1, 2, and change) and the wake-to-bed slope (Wave 2 and change) mediated these associations in men. Our results suggest that perceived stress and HPA-axis dysregulation could act as mechanisms underlying the association between neuroticism and cognitive functioning and decline, at least in older men. This article is protected by copyright. All rights reserved.
Construction of a Phytic Acid–Silica System in Wood for Highly Efficient Flame Retardancy and Smoke Suppression

The intrinsic flammability of wood restricts its application in various fields. In this study, we constructed a phytic acid (PA)–silica hybrid system in wood by a vacuum-pressure impregnation process to improve its flame retardancy and smoke suppression. The system was derived from a simple mixture of PA and silica sol. Fourier transform infrared spectroscopy (FTIR) indicated an incorporation of the PA molecules into the silica network. Thermogravimetric (TG) analysis showed that the system greatly enhanced the char yield of wood from 1.5% to 32.1% (in air) and the thermal degradation rates were decreased. The limiting oxygen index (LOI) of the PA/silica-nanosol-treated wood was 47.3%. Cone calorimetry test (CCT) was conducted, which revealed large reductions in the heat release rate and smoke production rate. The appearance of the second heat release peak was delayed, indicating the enhanced thermal stability of the char residue. The mechanism underlying flame retardancy was analyzed by field-emission scanning electron microscope coupled with energy-dispersive spectroscopy (SEM-EDS), FTIR, and TG-FTIR. The improved flame retardancy and smoke-suppression property of the wood are mainly attributed to the formation of an intact and coherent char residue with crosslinked structures, which can protect against the transfer of heat and mass (flammable gases, smoke) during burning. Moreover, the hybrid system did not significantly alter the mechanical properties of wood, such as compressive strength and hardness. This approach can be extended to fabricate other phosphorus and silicon materials for enhancing the fire safety of wood.