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pH-Dependent Electrocatalytic Aqueous Ammonia Oxidation to Nitrite and Nitrate by a Copper(II) Complex with an Oxidation-Resistant Ligand
3D fluorescence staining and confocal imaging of low amount of intestinal organoids (enteroids): Protocol accessible to all
The emerging field of 3D organ modeling encounters several imaging issues in particular related to antigen retrieval and sample loss during staining processes. Due to their compact shape, several antibodies fail to penetrate intact organoids or spheroids. Histology of organoids can be approached by paraffin inclusion and sectioning at 5 μm as performed for biopsies. However, to fully understand organoid behavior, including cellular organization, extracellular matrix structure, and their response to treatments, 3D imaging is essential. Here we propose an easy workflow allowing (1) immunostaining with a HIER step, (2) preservation of the intact shape of the organoids, (3) sample immobilization in a focal plane reachable for high resolution/short working distance lenses, and (4) minimizing the risk of loss of precious material.
Electrochemical Reduction of CO<sub>2</sub> to CH<sub>3</sub>OH Catalyzed by an Iron Porphyrinoid
Altered microbiome and metabolome profiling in fearful companion dogs: An exploratory study
Behavioral dysfunctions in dogs represent one of the main social concerns, since they can endanger animals and human-dog relationship. Together with the trigger stimulus (human, animal, place, scent, auditory stimuli, objects), dogs can experience stressful conditions, either in multiple settings or unique situations, more often turning into generalized fear. Such a dysfunctional behavior can be associated with genetic susceptibility, environmental factors, traumatic experiences, and medical conditions. The available therapy, based on behavior approaches, environmental management, and neurochemical manipulation, through nutrition, supplements, medicines, and pheromones, represent the mainstays of the treatments currently accessible. Growing evidence in humans and animals highlight the importance of the gut-brain axis in the modulation of the brain physiology and behavior as well. Here, taking advantage of the next generation sequencing approach, we sought to investigate the potential connection between gut microbiota and microbiome in dogs suffering from generalized fear (n = 8), when compared to healthy subjects (n = 8), who all lived in different families. Faecal microbiota evaluation showed a differential abundance of taxa related to Proteobacteria and Firmicutes Phyla, between case and control dogs. Moreover, serum metabolomics documented significant alterations of molecules associated to GABA and glutamate neurotransmission in the patients, as well as bile acids metabolism. Overall, our preliminary and integrated investigations highlighted an intriguing role for the microbiome-metabolome network, allowing to further unveil the potential pathophysiology of relational issues in companion animals and paving the way for more effective therapeutical approaches.
Near-Infrared Magnetic Circularly Polarized Luminescence and Slow Magnetic Relaxation in a Tetrazinyl-Bridged Erbium Metallocene
Modelling of online shopping behavior in the Czech online environment
The online environment has its own specifics, which shape the specific behavior of all market subjects, both customers and companies that trade electronically. The aim of the paper is to create, quantify and verify a conceptual comprehensive model of relationships between determinants that influence consumers when shopping online. The impetus for the conducted research was the discovery of the non-existence of a comprehensive model of online shopping behavior that reflects the specifics of the online environment. The main research method is the method of online questioning in the form of a questionnaire survey among a selected group of Czech respondents (n = 926) shopping online with the aim of evaluating the determinants of online shopping behavior. The results of the questionnaire survey are subsequently used to build a comprehensive model of online shopping behavior, which was statistically compiled and verified using the PLS-SEM method, which, based on statistical data, estimates the size and quality of the links between the measured (manifest) and assumed unmeasured (latent) variables. The results show that the selected factors (31 factors) explain up to 82.53% of the variability of the total variance. The results of the correlation analysis of the factors confirmed that the defined factors are not mutually dependent and that in the comprehensive model the factors are not only identified but also statistically significant. The results also confirmed that the correlation of e.g. psychological factors are stronger than dependence on other investigated factors in the comprehensive model of online shopping behavior. The research clearly showed that the key factors for customers when shopping online are Security and risk elimination (SE), together with the Online distribution and logistics (OD) and Online payments (OP). Impulsive online shopping was identified by customers as the least important factor. The validated model provides a comprehensive explanation of the current phenomenon of online shopping that integrates and extends previous studies identifying behavioral models of online shopping behavior.
Uranium Extraction from Seawater via Hydrogen Bond Porous Organic Cages
Nasal microbiota predictors for methicillin resistant Staphylococcus colonization in critically ill children
Background Surveillance cultures to identify patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) is recommended at pediatric intensive care unit (PICU) admission but doesn’t capture other methicillin-resistant Staphylococcus and is resource intensive. We determined the prevalence and identified nasal microbiome predictors for methicillin-resistant Staphylococcus colonization at the time of PICU admission. Study design A prospective cohort study was performed in a 20-bed pediatric intensive care unit (PICU) between 2020–2021. Anterior nares nasal swabs processed for MRSA culture, nasal microbiome and mecA+ qPCR were obtained within first five days after PICU admission. Predictive values of methicillin-resistant Staphylococcus carriage on symptoms of infection and for nasal microbiome attributes were calculated. Results A total of 5 (8.0%) of 62 patients had a nares culture positive for MRSA and 22 (35.5%) of 63 patients had methicillin-resistant Staphylococcus (MRSA or methicillin-resistant coagulase-negative Staphylococci). In univariate analysis, carriage with MRSA or MRCoNS was associated with having a fever during PICU stay. Colonization with a distinct set of microbes (including Haemophilus, Streptococcus, Prevotella and Corynebacterium sp.) was predictive of having methicillin-resistant Staphylococcus colonization. Conclusions Carriage with methicillin-resistant Staphylococcus may lead to transmission in critically ill pediatric patients. Carriage of particular nasal microbes appears to facilitate colonization with methicillin-resistant Staphylococcus.
A Single Bioorthogonal Reaction for Multiplex Cell Surface Protein Labeling
Correction: How long can tardigrades survive in the anhydrobiotic state? A search for tardigrade anhydrobiosis patterns
Precise Synthesis of 4.75 V-Tolerant LiCoO<sub>2</sub> with Homogeneous Delithiation and Reduced Internal Strain
Study of PEG-rhG-CSF for the prevention of neutropenia in concurrent chemoradiotherapy for nasopharyngeal carcinoma
Background To study the efficacy and safety of Polyethylene glycolated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in the prevention of neutropenia during concurrent chemoradiotherapy for nasopharyngeal carcinoma (NPC). Methods This is a single-center, prospective, randomized controlled study conducted from June 1, 2021, to October 31, 2022 on patients diagnosed with locally advanced NPC. Participants were divided into an experimental group and a control group. The experimental group received PEG-rhG-CSF injections post-chemotherapy cycles, whereas the control group received standard care without additional intervention. Outcomes assessed included grade 3/4 neutropenia incidence, blood cell count changes, febrile neutropenia rates, delays or interruptions in chemotherapy/radiotherapy due to hematological toxicity, oral mucositis incidents, and bone pain occurrences, comparing these between both groups. Results 1. 88 patients with locally advanced NPC were included, the incidence of grade 3 neutropenia in the experimental group was lower than that in the control group (P = 0.026); 2. The white blood cell count and neutrophil count in D7, D10, D14, and D21 in the experimental group were higher than those in the control group (P<0.01); 3. The rate of delayed chemotherapy in the experimental group was lower than that in the control group (2.3% vs. 29.5%), P = 0.001; the rate of interruption of radiotherapy in the experimental group was lower than that in the control group (2.3% vs.27.3%), P = 0.003; 4. The incidence of bone pain in the experimental group was 34.1%, of which most were mild bone pain, and no severe bone pain occurred. The leukocyte and neutrophil counts of the patients in the bone pain group were significantly higher than those of the patients in the no bone pain group, P(WBC) = 0.001, P(ANC) = 0.002. Conclusions The preventive use of PEG-rhG-CSF decreases the incidence of neutropenia in patients undergoing concurrent chemoradiotherapy for NPC, thereby reducing rates of chemotherapy delays and radiotherapy interruptions, with mild adverse reactions that are tolerable by patients.
Effects of Temperature Fluctuations on Surface Mobility of Atomic Steps and Oxidation Dynamics in High-Temperature Alloys
Determination of optimal gamma radiation dose for mutation breeding in ’Sabz’ fig (Ficus carica L.) cuttings based on radiosensitivity and phenotypic changes
The dried fig cv. Sabz of Iran, distinguishes out among the several fig cultivars for its unique characteristics and excellent properties. The aims to this study were 1) Carefully monitoring the resulting phenotypic changes in growth patterns, leaf morphology, shoot traits, root characteristics, and other relevant traits after irradiated with different gamma rays; 2) Investigating the LD25, 50, 75 and GR25, 50, 75 values at different gamma radiation doses for chose optimum dose. According to our results, the LD50 was 70 Gy, while the LD25 and LD75 were approximately 48 and 95 Gy, respectively. Data analysis revealed that higher doses, ranging from 50 to 90 Gy, led to a reduction in leaf area for fig hardwood cuttings compared to those exposed to lower doses of gamma irradiation (10, 20, 30, and 40 Gy). In fig cuttings, the plant height gradually decreased in line with increasing irradiation doses up to 60 Gy. Among the root traits, root number was particularly influenced by higher radiation doses. On other hand, when fig cuttings were exposed to a 40 Gy radiation dosage, the average root count dropped by 50%. However, when fig cuttings were subjected to a 90 Gy radiation dose, the average root count surged by 90.7% in comparison to the control treatment. Additionally, the GR50 values were 63 Gy for internode length, 67 Gy for leaf area and 56 Gy for plant height and aerial biomass. However, the GR50 values for root number, root volume, and root biomass were 46 Gy, 57 Gy, and 51 Gy, respectively. An analysis based on the GR25, GR50, and GR75 values indicated that plant height, aerial biomass and root biomass exhibited greater sensitivity to radioactivity in comparison to other plant portions of the fig. According to the biological responses in the ‘Sabz’ fig, 60 Gy of gamma radiation is a suitable dose for initial mutagenesis studies.
DNA Tetrahedron-Driven Multivalent Proteolysis-Targeting Chimeras: Enhancing Protein Degradation Efficiency and Tumor Targeting
Engineering dimer mutants of human geranylgeranyl pyrophosphate synthase
Geranylgeranyl pyrophosphate synthase (GGPPS), a key enzyme in protein prenylation, plays a critical role in cellular signal transduction and is a promising target for cancer therapy. However, the enzyme’s native hexameric quaternary structure presents challenges for crystallographic studies. The primary objective of this study was to engineer dimeric forms of human GGPPS to facilitate high-resolution crystallographic analysis of its ligand binding interactions. Through site-directed mutagenesis, we disrupted the inter-dimer interactions required for hexamer assembly, generating three stable double-site mutants: Y246D/C247L, Y246D/C205A, and Y246K/C247L. Enzyme assays confirmed that all mutants retained wild-type catalytic activity under both saturating and subsaturating substrate conditions. Differential scanning fluorimetry showed that the mutant proteins had a ~10°C lower melting temperature than the wild-type enzyme but exhibited similar shifts in melting temperature in the presence of the known inhibitors risedronate and zoledronate. Crystallographic analysis of the Y246D/C247L mutant yielded a 2.1 Å resolution structure, providing detailed insights into the binding of isopentenyl pyrophosphate. Closer inspection also revealed the unexpected formation of intermolecular disulfide bonds connecting neighboring dimers, which may explain the enhanced crystallizability of the Y246D/C247L mutant compared to the wild-type and other mutants. These findings highlight the potential of the dimeric mutants as substitutes for wild-type GGPPS in future studies. Optimized dimeric mutants could serve as valuable molecular tools to further our understanding of the enzyme’s structural and functional properties and aid in the rational design of novel therapeutic agents targeting GGPPS.
Dissecting the Molecular Structure of the Air/Ice Interface from Quantum Simulations of the Sum-Frequency Generation Spectrum
Gene expression analysis reveals mir-29 as a linker regulatory molecule among rheumatoid arthritis, inflammatory bowel disease, and dementia: Insights from systems biology approach
Background Rheumatoid arthritis (RA) is a degenerative autoimmune disease, often managed through symptomatic treatment. The co-occurrence of the reported extra-articular comorbidities such as inflammatory bowel disease (IBD), and dementia may complicate the pathology of the disease as well as the treatment strategies. Therefore, in our study, we aim to elucidate the key genes, and regulatory elements implicated in the progression and association of these diseases, thereby highlighting the linked potential therapeutic targets. Methodology Ten microarray datasets each for RA, and IBD, and nine datasets for dementia were obtained from Gene Expression Omnibus. We identified common differentially expressed genes (DEGs) and constructed a gene-gene interaction network. Subsequently, topology analysis for hub gene identification, cluster and functional enrichment, and regulatory network analysis were performed. The hub genes were then validated using independent microarray datasets from Gene Expression Omnibus. Results A total of 198 common DEGs were identified from which CD44, FN1, IGF1, COL1A2, and POSTN were identified as the hub genes in our study. These hub genes were mostly enriched in significant processes and pathways like tissue development, collagen binding, cell adhesion, regulation of ERK1/2 cascade, PI3K-AKT signaling, and cell surface receptor signaling. Key transcription factors TWIST2, CEBPA, EP300, HDAC1, HDAC2, NFKB1, RELA, TWIST1, and YY1 along with the miRNA hsa-miR-29 were found to regulate the expression of the hub genes significantly. Among these regulatory molecules, miR-29 emerged as a significant linker molecule, bridging the molecular mechanisms of RA, IBD, and dementia. Validation of our hub genes demonstrated a similar expression trend in the independent datasets used for our study. Conclusion Our study underscores the significant role of miR-29 in modulating the expression of hub genes and the associated transcription factors, which are crucial in the comorbidity status of RA, dementia, and IBD. This regulatory mechanism highlights miR-29 as a key player in the pathogenesis of these comorbid diseases.
Mechanistic Investigation of the Ce(III) Chloride Photoredox Catalysis System: Understanding the Role of Alcohols as Additives
Aligned membranes regulate wound healing via MMP12 secreted by macrophages
Aligned electrospinning membranes (Align) have demonstrated the potential to enhance wound healing by establishing a regenerative microenvironment surrounding the wound; However, the precise mechanism underlying its facilitation of healing remains unclear. To elucidate aligned electrospun fiber membrane’s role in accelerating wound healing and improving its quality, we conducted a comprehensive analysis. Firstly, in vivo experiments confirmed that Align promotes wound healing. Through combined bulk RNA sequencing and single-cell RNA sequencing, we identified that MMP12+ macrophages exhibit high expression of MMP12 during the early stage of wound remodeling, thereby inhibiting fibroblast migration and reducing scar formation after wound closure. Finally, both in vitro and in vivo experiments further validated the role of MMP12 in promoting wound healing and suppressing fibroblast migration. Our findings reveal that Align effectively enhances skin wound healing by upregulating MMP12 expression while inhibiting fibroblast migration. These insights provide valuable knowledge on how Align promotes efficient scar-free wound healing and serve as a theoretical foundation for developing more effective biological dressings.