Characterization of SNPs in meat quality-related genes in Argentine Coastal Creole pigs and their potential as a porcine genetic resource.

The Coastal Creole pigs in Argentina are predominantly found in the wild and can trace their lineage directly back to the Iberian breeds introduced by Spanish colonizers. They currently stand as the sole Creole breed in the country recognized by the FAO. However, there exists a dearth of studies assessing their genetic potential within the swine industry. Therefore, this study aimed to genetically characterize the meat quality of Coastal Creole pigs based on seven single nucleotide polymorphisms (SNPs) within the Ryr1, PRKAG3, MC4R, H-FABP, and CAST genes. A total of N = 158 samples were collected from specimens distributed along the coastal region. Our findings revealed all loci to exhibit polymorphism, underscoring the population's remarkable genetic diversity. Furthermore, a higher frequency of alleles favorable for the PRKAG3191I>V/200R>Q, MC4R1426A>G, CAST76872G>A, and Ryr11843C>T genes was observed, while alleles unfavorable predominated for H-FABP1811G>C and CAST638Ser>Arg. The results obtained in this research are highly encouraging, reflecting the genetic potential of these pigs to be utilized in swine production programs.

Icariin suppresses osteogenic differentiation and promotes bone regeneration in Porphyromonas gingivalis-infected conditions through EphA2-RhoA signaling pathway.

Periodontitis is associated with multiple systemic diseases and can cause bone loss. Porphyromonas gingivalis (P. gingivalis) is one of the most virulent periodontal pathogens. Icariin is a flavonoid extracted from the traditional Chinese herbal medicine Herba Epimedii, and can regulate bone metabolism. However, its effects on promoting bone metabolism have not been fully elucidated. In this experiment, we infected MC3T3-E1 cells with P. gingivalis. Flow cytometry results show that persistent bacterial infection does not affect cell proliferative activity. Western blotting, ALP activity detection, mineral content determination, and immunofluorescence blotting confirmed that icariin improved osteogenic differentiation in the inflammatory state, and this effect may be more obvious in the early stage of osteogenic differentiation. The antibacterial assays, ROS and MMP fluorescence assays demonstrated that icariin exerted a significant inhibitory effect on bacterial growth and attenuated the inflammatory response in bacterial-infected conditions. The results of in vivo experiments in animals further validated the excellent properties exerted by icariin in the repair of bone defects. Additionally, in the P. gingivalis-infected state, icariin exert a regulatory effect on EphA2-RhoA signaling pathway to augment osteogenic differentiation. These exciting findings suggest that icariin holds significant potential for therapeutic application in the management of periodontal bone loss.

Soy Peptide Ameliorate TGF-ß1-Mediated Osteoblast Differentiation through Smad and MAPK Signaling Pathways.

The aim of this study was to determine the osteogenic activity and mechanism of soybean peptide VVELLKAFEEKF (SOP) and the potential relationship between SOP and transforming growth factor-ß1 (TGF-ß1). The results show that SOP promotes MC3T3-E1 cell proliferation by altering cell progression. SOP induced cell differentiation and mineralization in a dose-dependent manner at 0.7-7 µM. Moreover, SOP stimulates osteoblast differentiation, which may be achieved through the activation of p38-MAPK and Smad2/3 signaling pathways. Furthermore, treatment with a TßRI inhibitor (SB525334) inhibited the phosphorylation levels of p38 and Smad2/3, which indicates the involvement of TßRI in the process of osteoblast differentiation caused by SOP. Besides, in non-FBS-cultured MC3T3-E1 cells, SOP and TGF-ß1 promoted the phosphorylation of Smad2/3 and alkaline phosphatase (ALP) activity, but the effect was lost when SOP was incubated separately, indicating that SOP stimulated osteoblast differentiation by promoting TGF-ß1 activity. In vivo, SOP significantly restores bone mineral density loss and behavioral deficits in a model of glucocorticoid-induced osteoporosis (GIOP) in zebrafish. These results suggest that SOP may have the function of promoting bone remodeling and may be used as a potential active factor for functional food development to prevent osteoporosis.

Development of a Physiologically Based Pharmacokinetic (PBPK) Model for F-53B in Pregnant Mice and Its Extrapolation to Humans.

Chlorinated polyfluorinated ether sulfonic acid (F-53B), a commonly utilized alternative for perfluorooctane sulfonate, was detected in pregnant women and cord blood recently. However, the lack of detailed toxicokinetic information poses a significant challenge in assessing the human risk assessment for F-53B exposure. Our study aimed to develop a physiologically based pharmacokinetic (PBPK) model for pregnant mice, based on toxicokinetic experiments, and extrapolating it to humans. Pregnant mice were administered 80 µg/kg F-53B orally and intravenously on gestational day 13. F-53B concentrations in biological samples were analyzed via ultraperformance liquid chromatography-mass spectrometry. Results showed the highest F-53B accumulation in the brain, followed by the placenta, amniotic fluid, and liver in fetal mice. These toxicokinetic data were applied to F-53B PBPK model development and evaluation, and Monte Carlo simulations were used to characterize the variability and uncertainty in the human population. Most of the predictive values were within a 2-fold range of experimental data (>72%) and had a coefficient of determination (R2) greater than 0.68. The developed mouse model was then extrapolated to the human and evaluated with human biomonitoring data. Our study provides an important step toward improving the understanding of toxicokinetics of F-53B and enhancing the quantitative risk assessments in sensitive populations, particularly in pregnant women and fetuses.

AEBP1 restores osteoblastic differentiation under dexamethasone treatment by activating PI3K/AKT signalling.

Adipocyte enhancer-binding protein 1 (AEBP1) is closely implicated in osteoblastic differentiation and bone fracture; this research aimed to investigate the effect of AEBP1 on restoring osteoblastic differentiation under dexamethasone (Dex) treatment, and its interaction with the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. Pre-osteoblastic MC3T3-E1 cells were cultured in osteogenic medium and treated by Dex to mimic steroid-induced osteonecrosis cellular model. They were then further transfected with control or AEBP1-overexpressed lentiviral vectors. Finally, cells were treated with the PI3K inhibitor LY294002, with or without AEBP1-overexpressed lentiviral vectors. AEBP1 expression showed a downward trend in MC3T3-E1 cells under Dex treatment in a dose-dependent manner. AEBP1-overexpressed lentiviral vectors increased relative cell viability, alkaline phosphatase (ALP) staining, Alizarin red staining and osteoblastic differentiation markers including osteocalcin (OCN), osteopontin (OPN), collagen type I alpha 1 (COL1A1), runt-related transcription factor 2 (RUNX2) and bone morphogenetic protein 2 (BMP2), but decreased cell apoptosis rate in MC3T3-E1 cells under Dex treatment; besides, AEBP1-overexpressed lentiviral vectors positively regulated p-PI3K and p-AKT expressions. Furthermore, LY294002 treatment decreased relative cell viability, Alizarin red staining, osteoblastic differentiation markers including OCN, OPN, RUNX2 and BMP, increased cell apoptosis rate and did not affect ALP staining in MC3T3-E1 cells under Dex treatment; meanwhile, LY294002 treatment weakened the effect of AEBP1 overexpression vectors on the above cell functions. AEBP1 restores osteoblastic differentiation under Dex treatment by activating the PI3K/AKT pathway.

Extraction Condition Optimization, Quantitative Analysis, and Anti-AD Bioactivity Evaluation of Acorn Polyphenols from Quercus variabilis, Quercus aliena, and Quercus dentata.

In the present study, Quercus variabilis (Q. variabilis), Quercus aliena (Q. aliena), and Quercus dentata (Q. dentata) acorn kernels were taken as the research objects, and the free polyphenols and bound polyphenols in acorn kernels were extracted using improved ultrasound-assisted ethanolic and alkaline extraction methods, after which the contents of gallic acid, quercetin, azelaic acid, ellagic acid, and ferulic acid were quantified by LC-MC/MS. The results demonstrated that Q. variabilis and Q. aliena acorns were suitable as raw materials to extract ellagic acid, the contents of ferulic acid and bound gallic acid in them were different, and Q. aliena acorns were more suitable for the research of gallic acid, but not for azelaic acid. Results on APP/PS1 transgenic mice verified that five polyphenols significantly suppressed the progression of AD. This study provides a theoretical basis for the drug development of acorn polyphenols.

An ANI-2 enabled open-source protocol to estimate ligand strain after docking.

In protein-ligand docking, the score assigned to a protein-ligand complex is approximate. Especially, the internal energy of the ligand is difficult to compute precisely using a molecular mechanics based force-field, introducing significant noise in the rank-ordering of ligands. We propose an open-source protocol (https://github.com/UnixJunkie/MMO), using two quantum mechanics (QM) single point energy calculations, plus a Monte Carlo (Monte Carlo) based ligand minimization procedure in-between, to estimate ligand strain after docking. The MC simulation uses the ANI-2x (QM approximating) force field and is performed in the dihedral space. On some protein targets, using strain filtering after docking allows to significantly improve hit rates. We performed a structure-based virtual screening campaign on nine protein targets from the Laboratoire d'Innovation Thérapeutique-PubChem assays dataset using Cambridge crystallographic data centre genetic optimization for ligand docking. Then, docked ligands were submitted to the strain estimation protocol and the impact on hit rate was analyzed. As for docking, the method does not always work. However, if sufficient active and inactive molecules are known for a given protein target, its efficiency can be evaluated.

Using a Dual-Disease Target Mapping Network Pharmacology Approach, Verbascoside Ameliorates Osteoporosis by Activating Estrogen Signaling to Alleviate Oxidative Stress.

BACKGROUND: Verbascoside, a compound classified as a phenylethanol glycoside in Dihuang, has been the subject of modern pharmacological investigations. These studies have revealed its noteworthy antioxidant, anti-inflammatory, memory-enhancing, neuroprotective, antitumor, and various other pharmacological properties. While verbascoside exhibits favorable antioxidant effects, its precise mechanism of action in ameliorating osteoporosis through the treatment of oxidative stress remains unclear. METHODS: This study employed CCK8, ALP, ELISA, and ROS staining techniques to examine the osteoporotic effects of verbascoside on zebrafish and MC3T3-E1 cells. Additionally, this study aimed to investigate the molecular mechanism by which verbascoside improves osteoporosis by mitigating oxidative stress. To identify the common targets of verbascoside in relation to oxidative stress and osteoporosis, network pharmacology and molecular dynamics simulation were employed. The construction of the verbascoside - oxidative stress - osteoporosis - potential target gene network aimed to identify the core targets, while the mechanism of action was elucidated through KEGG analysis, and the accuracy was confirmed by assessing the mRNA expression of the targets. RESULTS: In vivo experiments demonstrated that verbascoside exhibited therapeutic effects on osteoporosis and reduced ROS production in zebrafish. In vitro experiments further revealed that verbascoside enhanced the proliferation and differentiation of MC3T3-E1 cells, thereby improving the oxidative stress status of osteoblasts. Thirteen core targets and estrogen signaling pathways were identified through the application of network pharmacology. The pivotal role of the estrogen signaling pathway in facilitating the ability of verbascoside to mitigate oxidative stressinduced osteoporosis was substantiated by the modulation of target protein mRNA expression. CONCLUSION: The findings underscore the considerable therapeutic potential of verbascoside in ameliorating osteoporosis through the alleviation of oxidative stress, thus establishing it as a promising compound for the treatment of this condition.

Geochemical fingerprinting of Norway spruce from the Eastern Carpathians: Sr isotopic and multi-elemental signatures.

Ensuring efficient wood traceability within procurement chains is essential for establishing sustainable forest management and minimizing environmental damage in countries that produce and export timber. While some progress has been made with key legislative reforms to tackle this issue, the effectiveness of law enforcement still relies on the availability of appropriate analytical tools to determine the provenance of wood. This study documents the Sr isotopic and multi-elemental signatures of Norway spruce trees in the Eastern Carpathians, Romania - an area known for intensive forest logging. The research focused on trees from Rodna, Rarau, and Calimani, analyzing tree rings from 1970 to 2020 to assess temporal variability and develop site-specific geochemical fingerprints. In conjunction with tree samples, corresponding soil, groundwater, and river samples were analyzed, providing a comprehensive view of the bioavailable 87Sr/86Sr ratios in these ecosystems. The study found a strong correlation between the Sr isotope ratios in the wood and those in corresponding water and soil samples, confirming that the wood accurately mirrors local geochemical signatures. The Sr isotope ratios were consistent across most of the cores from trees within the same site but varied among sites within the same region. Principal Component Analysis of the Sr isotopic and multi-elemental data highlighted closer clustering of samples from the Calimani area, though distinguishing the samples from the Rodna and Rarau regions proved more difficult due to overlapping data points. This study broadens our understanding of geochemical variability and its implications. The insights gained provide a valuable foundation for future research aimed at enhancing wood traceability methods.

Role of histone deacetylases and their inhibitors in neurological diseases.

Histone deacetylases (HDACs) are zinc-dependent deacetylases that remove acetyl groups from lysine residues of histones or form protein complexes with other proteins for transcriptional repression, changing chromatin structure tightness, and inhibiting gene expression. Recent in vivo and in vitro studies have amply demonstrated the critical role of HDACs in the cell biology of the nervous system during both physiological and pathological processes and have provided new insights into the conduct of research on neurological disease targets. In addition, in vitro and in vivo studies on HDAC inhibitors show promise for the treatment of various diseases. This review summarizes the regulatory mechanisms of HDAC and the important role of its downstream targets in nervous system diseases, and summarizes the therapeutic mechanisms and efficacy of HDAC inhibitors in various nervous system diseases. Additionally, the current pharmacological situation, problems, and developmental prospects of HDAC inhibitors are described. A better understanding of the pathogenic mechanisms of HDACs in the nervous system may reveal new targets for therapeutic interventions in diseases and help to relieve healthcare pressure through preventive measures.

COVID-19 vaccination anti-cancer impact on the PI3K/AKT signaling pathway in MC4L2 mice models.

The most promising method of containing the COVID-19 pandemic is considered to be vaccination against SARS-CoV-2 infection. However, research on the relationship between vaccination against COVID-19 and cancer has primarily examined induced immunity rather than the disease itself. Considering that breast cancer is the most common cancer among women, the main goal of this study was to examine the impact of the Sinopharm and AstraZeneca vaccination on tumor characteristics such as tumor size, important tumor markers, tumor-infiltrating lymphocytes, metastasis to vital organs, and investigation of the PI3K/AKT signaling pathway, and the expression levels of relevant genes (PTEN, mTOR, AKT, PI3K, GSK3, and FoxO1) of the luminal B (MC4L2) mouse model. The tumor size of the mice was measured and monitored every two days, and after thirty days, the mice were euthanized. Remarkably, after vaccination, all vaccinated mice showed a decrease in the size of their tumor and an increase in the number of lymphocytes that had invaded the tumors. Tumor marker levels (VEGF, Ki-67, MMP-2/9), CD4/CD8 ratio, metastasis to vital organs, hormone receptors (ER, PR, and HER-2), and expression of genes related to the advancement of the PI3K/AKT signaling pathway were lower in vaccinated mice. Our research showed that the COVID-19 vaccine can have an anti-cancer effect by slowing the tumor progression and metastasis.

Microdosimetric Simulation of Gold-Nanoparticle-Enhanced Radiotherapy.

Conventional X-ray therapy (XRT) is commonly applied to suppress cancerous tumors; however, it often inflicts collateral damage to nearby healthy tissue. In order to provide a better conformity of the dose distribution in the irradiated tumor, proton therapy (PT) is increasingly being used to treat solid tumors. Furthermore, radiosensitization with gold nanoparticles (GNPs) has been extensively studied to increase the therapeutic ratio. The mechanism of radiosensitization is assumed to be connected to an enhancement of the absorbed dose due to huge photoelectric cross-sections with gold. Nevertheless, numerous theoretical studies, mostly based on Monte Carlo (MC) simulations, did not provide a consistent and thorough picture of dose enhancement and, therefore, the radiosensitization effect. Radiosensitization by nanoparticles in PT is even less studied than in XRT. Therefore, we investigate the physics picture of GNP-enhanced RT using an MC simulation with Geant4 equipped with the most recent physics models, taking into account a wide range of physics processes relevant for realistic PT and XRT. Namely, we measured dose enhancement factors in the vicinity of GNP, with diameters ranging from 10 nm to 80 nm. The dose enhancement in the vicinity of GNP reaches high values for XRT, while it is very modest for PT. The macroscopic dose enhancement factors for realistic therapeutic GNP concentrations are rather low for all RT scenarios; therefore, other physico-chemical and biological mechanisms should be additionally invoked for an explanation of the radiosensitization effect observed in many experiments.

Comparative Measurement of Citizens' Perceptions of Local Policies: A 3MC (Multinational, Multicultural, Multiregional) Approach.

Comparative social policy research continues to face considerable methodological challenges. Scholars particularly struggle to capture sub-national policy variation in comparatively reliable ways, including subjective perceptions of local policies. Local-level variation increases the need for conceptual and methodological attention to comparability across differing national, cultural, and linguistic settings. The article outlines a conceptually grounded approach relying on the 3MC (multinational, multicultural, multiregional) method to measure and compare individual perceptions of local policies cross-nationally. Often applied in cross-national survey research, a 3MC approach can help address methodological challenges inherent in comparative policy research and improve cross-national studies of local policy differences.

Variability of theory of mind versus pragmatic ability in typical and atypical development.

INTRODUCTION: Numerous studies have linked deficits in Theory of Mind (ToM) with language problems. We aimed to explore the similarities and differences between children's patterns of performance on a ToM task that requires minimal linguistic skill and a pragmatic inference task that relies on both ToM and language. We assessed variability in pragmatic inference skills and ToM across populations of children (8-14 years) displaying varying cognitive profiles. We further compared the sensitivity of ToM versus pragmatic ability to core language skills, memory and executive functioning (EF). METHOD: ToM was tested using the Social Attribution Task (SAT-MC-II). Pragmatic ability was assessed in an implicature comprehension task. Receptive vocabulary, grammar comprehension, short-term and working memory (STM and WM) capacity and EF were measured using Hungarian adaptations of standard tasks and tests developed by the authors' lab. In addition to typically developing (TD) children (n = 33), we included children with neurodevelopmental disorders where ToM and/or language abilities are vulnerable: autism spectrum disorder (ASD, n = 26), attention deficit hyperactivity disorder (ADHD, n = 25) and developmental language disorder (DLD, n = 18). RESULTS: Results revealed a significant but only moderate positive correlation between pragmatic inference and ToM indicating that the two abilities are related but distinct. The ASD group showed impairments in both ToM and pragmatic inference ability but no significant deficit was observed in ADHD or DLD relative to TD children in either skill. However, while SAT-MC-II results were only affected by verbal WM and vocabulary measures, pragmatic performance was associated with STM, verbal WM, EF, grammatical skills and vocabulary. CONCLUSION: Our findings indicate that disentangling the contributions of different cognitive skills to ToM tasks may help clarify the role of ToM in language skills and identify distinct patterns of ToM and pragmatic skills in developmental disorders.

Melatonin Regulates Osteoblast Differentiation through the m6A Reader hnRNPA2B1 under Simulated Microgravity.

Recent studies have confirmed that melatonin and N6-methyladenosine (m6A) modification can influence bone cell differentiation and bone formation. Melatonin can also regulate a variety of biological processes through m6A modification. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) serves as a reader of m6A modification. In this study, we used the hindlimb unloading model as an animal model of bone loss induced by simulated microgravity and used 2D clinorotation to simulate a microgravity environment for cells on the ground. We found that hnRNPA2B1 was downregulated both in vitro and in vivo during simulated microgravity. Further investigations showed that hnRNPA2B1 could promote osteoblast differentiation and that overexpression of hnRNPA2B1 attenuated the suppression of osteoblast differentiation induced by simulated microgravity. We also discovered that melatonin could promote the expression of hnRNPA2B1 under simulated microgravity. Moreover, we found that promotion of osteoblast differentiation by melatonin was partially dependent on hnRNPA2B1. Therefore, this research revealed, for the first time, the role of the melatonin/hnRNPA2B1 axis in osteoblast differentiation under simulated microgravity. Targeting this axis may be a potential protective strategy against microgravity-induced bone loss and osteoporosis.

Insight into the Structural and Magnetic Properties of PrZnSi and NdZnSi Compounds Featuring Large Low-Temperature Magnetocaloric Effects.

The magnetocaloric (MC) and magnetic phase transition (MPT) properties in various types of rare earth (RE)-based magnetic materials have been intensively investigated recently, which are aimed at developing suitable MC materials for low-temperature cooling applications and better elucidating their inherent physical properties. We herein provide a combined experimental and theoretical investigation into two new light RE-based magnetic materials, namely, PrZnSi and NdZnSi compounds, regarding their structural, magnetic, MPT, and low-temperature MC properties. Both of these compounds crystallize in an AlB2-type hexagonal structure with a symmetry of the crystallographic space group P6/mmm and reveal a typical second-order-type MPT with ordering temperatures (TC) at approximately 13.5 and 18.5 K for PrZnSi and NdZnSi compounds, respectively. Moreover, they all exhibit large reversible low-temperature MC effects and remarkable performances, which are identified by the parameters of maximum magnetic entropy changes, relative cooling power, and temperature-averaged entropy change (temperature lift 5 K). The deduced values of these MC parameters under a magnetic field change of 0-7 T reach 16.3 J/kgK, 294.46 J/kg, and 15.79 J/kgK for PrZnSi and 15.4 J/kgK, 284.84 J/kg, and 14.95 J/kgK for NdZnSi, respectively, which are evidently better than those of most updated light RE-based magnetic materials with remarkable low-temperature MC performances, indicating that PrZnSi and NdZnSi compounds hold potentials for practical cooling applications.

Effects of electron density force to 1.0 and fill to 1.0 on VMAT treatment plans for lung SBRT.

PURPOSE: The aim of this study is to determine the effect of forcing and filling the electron density (ED) to 1.0 of the planning target volume (PTV) overdose distribution in lung SBRT treatment leading to shortening patient treatment time and increasing patient comfort by reducing MU/fraction due to ED manipulation effect. METHODS: In this study, 36 lung SBRT plans of 12 suitable patients who prescribed a total dose of 50 Gy in five fractions were generated with Monaco v.5.10 TPS using the Monte Carlo (MC) algorithm and volumetric modulated arc therapy (VMAT) technique by PTV ED values forcing as well as filling to 1.0 and comparatively assessed. The first group of plans was created by using the patient's original ED, second and third groups of plans were reoptimized by forcing and filling the ED of PTV to 1.0, respectively, therefore acquiring a new dose distribution which lead to comparatively assessment the effects of changes in ED on PTV and OAR doses. RESULTS: Assessment of treatment plans revealed that mean MU/fx numbers were decreased by 76% and 75.25% between Groups 1 and 2, Groups 1 and 3, respectively. The number of segments was also reduced in Group 1 by up to 15% compared with Groups 2 and 3. Maximum HI and CI differences for PTV between Groups 1 and 2 were less than 1% and Groups 1 and 3 were 1.5% which indicates all 3 group plans were comparable in terms of dose distribution within PTV. CONCLUSIONS: Forcing and filling the ED of PTV to 1.0 strategy has provided reduced a number of segments and MU/fx without a significant change in PTV mean and maximum doses, thereby decreasing treatment time and patient discomfort during treatment. This process should be considered in line of a potential number of patients as well as prescribed dose and MU/fx numbers.

DNA 5mC and RNA m6A Collaborate to Upregulate Phosphoenolpyruvate Carboxykinase 2 for Kupffer Cell Activation.

Both DNA 5-methylcytosine (5mC) and RNA N6-methyladenosine (m6A) modifications are reported to participate in cellular stress responses including inflammation. Phosphoenolpyruvate carboxykinase 2 (PCK2) is upregulated in Kupffer cells (KCs) to facilitate the proinflammatory phosphorylation signaling cascades upon LPS stimulation, yet the role of 5mC and m6A in PCK2 upregulation remain elusive. Here, we report that the significantly augmented PCK2 mRNA and protein levels are associated with global 5mC demethylation coupled with m6A hypermethylation in LPS-activated KCs. The suppression of 5mC demethylation or m6A hypermethylation significantly alleviates the upregulation of PCK2 and proinflammatory cytokines in LPS-challenged KCs. Further reciprocal tests indicate 5mC demethylation is upstream of m6A hypermethylation. Specifically, CpG islands in the promoters of PCK2 and RNA methyltransferase (METTL3 and METTL14) genes are demethylated, while the 3'UTR of PCK2 mRNA is m6A hypermethylated, in LPS-stimulated KCs. These modifications contribute to the transactivation of the PCK2 gene as well as increased PCK2 mRNA stability and protein production via a m6A-mediated mechanism with IGF2BP1 as the reader protein. These results indicate that DNA 5mC and RNA m6A collaborate to upregulate PCK2 expression, respectively, at the transcriptional and post-transcriptional levels during KC activation.

Effects of elevated intraocular pressure on alpha ganglion cells in experimental glaucoma mice.

Glaucoma is a leading cause of blindness worldwide and glaucoma patients exhibit an early diffuse loss of retinal sensitivity followed by focal loss of RGCs. Combining some previous published results and some new data, this paper provides our current view on how high IOP (H-IOP) affects the light response sensitivity of a subset of RGCs, the alpha-ganglion cells (αGCs), as well as their presynaptic bipolar cells (DBCs and HBCs) and A2 amacrine cells (AIIACs) in dark-adapted mouse retinas. Our data demonstrate that H-IOP in experimental glaucoma mice significantly decreases light-evoked spike response sensitivity of sONαGCs and sOFFαGCs (i.e., raises thresholds by 1.5-2.5 log units), but not that of the tONαGCs and tOFFαGCs. The sensitivity loss in sONαGCs and sOFFαGCs is mediated by a H-IOP induced suppression of AIIAC response which is caused by a decrease of transmission efficacy of the DBCR→AIIAC synapse. We also provide evidence supporting the hypothesis that BK channels in the A17AC→DBCR feedback synapse are the H-IOP sensor that regulates the DBCR→AIIAC synaptic efficacy, as BK channel blocker IBTX mimics the action of H-IOP. Our results provide useful information for designing strategies for early detection and possible treatments of glaucoma as physiological changes occur before irreversible structural damage.

Landscape transition-induced ecological risk modeling using GIS and remote sensing techniques: a case of Saint Martin Island, Bangladesh.

Uncontrolled human activity and nature are causing the deterioration of Saint Martin Island, Bangladesh's only tropical island, necessitating sustainable land use strategies and ecological practices. Therefore, the present study measures the land use/cover transition from 1974 to 2021, predicts 2032 and 2042, and constructs the spatiotemporal features of the Landscape Ecological Risk Index based on land use changes. The study utilized Maximum Likelihood Classification (MLC) on Landsat images from 1974, 1988, 2001, 2013, and Sentinel 2B in 2021, achieving ≥ 80% accuracy. The MLP-MC approach was also used to predict 2032 and 2042 LULC change patterns. The eco-risk index was developed using landscape disturbance and vulnerability indices, Bayesian Kriging interpolation, and spatial autocorrelations to indicate spatial clustering. The research found that settlements increased from 2.06 to 28.62 ha between 1974 and 2021 and would cover 41.22 ha in 2042, causing considerable losses in agricultural areas, waterbodies, sand, coral reefs, and vegetation. The area under study showed a more uniform and homogenous environment as Shannon's diversity and evenness scores decreased. The ecological risk of Saint Martin Island increased from 4.31 to 31.05 ha between 1974 and 2042 due to natural and human factors like erosion, tidal bores, population growth, coral mining, habitat destruction, and intensive agricultural practices and tourism, primarily in Nazrul Para, Galachipa, and Western Dakhin Para. The findings will benefit St. Martin Island stakeholders and policymakers by providing insights into current and potential landscape changes and land eco-management.