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关键词： Prebiotics   Oligosaccharides   Agro-industrial residues   Gut microbiota   In vitro fermentation   SCFAs   ANCOM-BC   Analysis of Compositions of Microbiomes with Bias Correction   AOS   Arabinooligosaccharides   BCFAs   Branched-chain fatty acids   C   Positive control   C   Negative control   DA   Degree of acetylation   DM   Degree of methylation   DP   Degree of polymerization   EPH   Enzymatic posthydrolysis   F/B   Firmicutes-to-Bacteroidota ratio   FDR   False discovery rate   FOS   Fructooligosaccharides   FTIR   Fourier Transform Infrared Spectroscopy   GAE   Gallic acid equivalents   GC   Gas chromatography   GGMOS   Galactoglucomannooligosaccharides   GHs   Glycosyl hydrolases   GM   GOS   Galactooligosaccharides   HPAEC-PAD   High Performance Anion Exchange Chromatography with Pulsed Amperometric Detection   HPLC   High performance liquid chromatography   IBD   Inflammatory Bowel Disease   ISAPP   International Scientific Association for Probiotics and Prebiotics   LEfSe   Linear discriminant analysis Effect Size   LDA   Linear discriminant analysis   LPOS   Lemon pectooligosaccharides   MALDI-TOF (MS)   Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry   MS   Monosaccharides   m/z   Mass-to-charge ratio   NVC   Non-volatile content   OGalA   Oligogalacturonides   OS   PBS   Phosphate-buffered saline   PCoA   Principal coordinates analysis   PCA   Principal component analysis   PLS-DA   Partial least squares discriminant analysis   QAPH   Quantitative acid posthydrolysis   RA   Relative abundance   RG-I   Rhamnogalacturonan I   RI   Refractive index   SBPOS   Sugar beet pectooligosaccharides   Short-chain fatty acids   SGF   Simulated gastric fluid   SIF   Simulated intestinal fluid   SSF   Simulated salivary fluid   TPC   Total phenolic content   TSS   Total sum scaling   v/v   Volume per volume   w/v   Weight per volume   w/w   Weight per weight   XOS   Xylooligosaccharides  

摘要：

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  SBPOS, GGMOS, and LPOS tested remain stable after INFOGEST digestion.
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  SBPOS promotes a balanced profile oriented toward acetate production.
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  SBPOS preserves microbial alpha diversity and community structure.
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  LPOS and GGMOS exhibit higher SCFA yields per gram of substrate consumed.
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  LPOS fermentation significantly enhances polyphenol bioavailability.

关键词： Neuroinflammation   Neurophysiology   Interleukin 1   Interleukin 1 receptor antagonist   Neuronal dendrites   RNA-sequencing  

摘要： Perinatal inflammation, often caused by bacterial infection, is strongly linked with lifelong disability. We tested the hypothesis that IL-1 is a key mediator of inflammatory injury and evaluated whether systemic administration of IL-1 receptor antagonist (IL-1Ra) could attenuate cortical inflammation and improve neuronal development in late gestation fetal sheep exposed to TLR-4 mediated inflammation with lipopolysaccharide (LPS). Fetal sheep of both sexes, instrumented for continuous EEG, were randomised to: (1) saline infusion, (2) repeated intravenous LPS + vehicle infusions or (3) the same LPS regimen plus intravenous IL-1Ra infusions 1 h after each LPS dose. Four days later, brains were examined using RNA-seq, Golgi staining and immunohistochemistry. On EEG, LPS-exposure reduced relative beta power (high frequency EEG activity) compared to control, particularly in rapid eye movement sleep. In the somatosensory cortex, LPS-exposure decreased expression of genes involved in dendritogenesis and synaptogenesis, and increased genes involved in immune activation via LPS and IL-1 signalling. LPS-exposed fetuses had increased microglial activation and reduced neuronal arborisation. IL-1Ra treatment improved relative beta power, upregulated expression of genes involved in synaptogenesis, dendritogenesis and immune activation, reduced microglial activation, and improved neuronal arborisation. In summary, these findings indicate that IL-1 is a key driver of cortical neuronal injury associated with fetal inflammation and that IL-1Ra may improve neurodevelopmental outcomes following perinatal infection/inflammation.

关键词： Müller glia   Glucose transporter   PI3K/AKT   HIV-1 TAT   Retina   Oxidative stress   Metabolism   AKT   PKB Protein kinase B   p-AKT   Phospho-AKT   Glut1   Glucose transporter type 1   Phosphatidylinositol-4,5-bisphosphate 3-kinase   2-NBDG   2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl) Amino)-2-Deoxyglucose   8-OHdG   8 hydroxy 2-deoxy guanosine   ART   Anti-retroviral therapy   TAT   Trans-Activator of Transcription   CRALBP   Cellular retinaldehyde-binding protein   KOBAS   KEGG Orthology-Based Annotation System   DMEM   Dulbecco's Modified Eagle's Medium   GFAP   Glial fibrillary acidic protein   DAPI   4′,6-diamidino-2-phenylindole   PBS   Phosphate Buffer Saline   PLHIV   People living with HIV  

摘要：

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  TAT activated Muller glia show changes in Redox functions, mitochondrial potential and 8 hydroxy 2-deoxy guanosine early on exposure to HIV TAT.
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  High glycolytic activity in retinal Muller glia associated with changes associated aging and immune-metabolism in activated retinal Muller cells
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  Microarray data genes display association of metabolism and mitochondrial function along with aging markers in activated Muller glia.
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  Glut 1 expression increases upon HIV1 TAT exposure which is reversed by PI3K inhibitor (LY294002) in Muller glia.

关键词： Prostate cancer   PSMA   Nanoplasmid   DNA vaccine  

摘要： Prostate cancer (PCa) remains a leading cause of cancer-related mortality among men particularly in metastatic castration-resistant disease, which is refractory to immune checkpoint blockade. Prostate-specific membrane antigen (PSMA) is highly overexpressed and correlated with PCa aggressiveness and invasiveness. In this study, we evaluated the prophylactic and therapeutic potential of a next generation Nanoplasmid-based DNA vaccine encoding human PSMA (N-hPSMA). We demonstrated that Nanoplasmid resulted in faster, higher, and more sustained transgene expression compared with a conventional plasmid vector, which led to a significant increase in hPSMA-specific cellular and humoral immune response. Prophylactic vaccination conferred tumor eradication and prevented lung metastasis. N-hPSMA vaccination increased systemic immune activation with abated regulatory T cell population and augmentation of effector-memory CD8⁺ T cells. In the therapeutic setting, N-hPSMA slowed tumor growth and potentiated PD-1 blockade, resulting in enhanced tumor regression and survival, while increasing activation of myeloid antigen presenting cells. In a humanized orthotopic PCa model, N-hPSMA vaccination plus PD-1 blockade significantly increased functional human CD8⁺ T cells and suppressed the growth of human PCa LNCaP tumors. These findings established N-hPSMA as a preclinical proof-of-concept DNA vaccine that enhances antitumor immunity and sensitizes PCa to immune checkpoint blockade.

关键词： PAHs   Hydroxy-PAHs   Oxy-PAHs   Nitro-PAHs   In vitro AhR cell-based bioassays   Relative effect potency (REP)  

摘要： Environmental monitoring of polycyclic aromatic hydrocarbons (PAHs) and their derivatives (e.g., oxy- and nitro-PAHs) remains challenging due to their chemical diversity and the limitations of targeted chemical analyses, which capture only a subset of compounds and cannot address mixture effects. Aryl hydrocarbon receptor (AhR)-based in vitro bioassays have therefore emerged as key complementary tools that integrate the biological activity of all AhR-active compounds in a sample. Linking chemical and biological data requires investigating the AhR activity of individual compounds and determining bioassay-specific relative effect potencies (REPs), which remain unavailable for many environmentally relevant PAH derivatives. This study aims to comprehensively characterize the in vitro AhR-mediated activity for 64 individual compounds, including 17 parent PAHs, 6 hydroxy-PAHs, 21 oxy-PAHs, 16 nitro-PAHs, and 4 p-phenylenediamine (PPD) quinones, and derive their REPs using two AhR-responsive cell lines (human HepG2 and fish PLHC-1). Out of the 64 compounds tested, 27 induced AhR activity in at least one cell assay, with compound-, cell line-, and exposure time-dependent differences being observed. Medium to high-molecular-weight parent PAHs (4–6 rings) and a few derivatives showed the highest potencies, whereas other compounds were weakly active or inactive. PLHC-1 cells were more sensitive to parent PAHs, HepG2 cells to oxy-PAHs, and nitro-PAHs elicited broadly comparable responses using both cell lines. By expanding AhR activity data for numerous previously uncharacterized PAH derivatives and emerging contaminants, this study provides a harmonized reference dataset to support mass balance, structure-activity analyses, and enhance effect-based hazard evaluation of complex PAC mixtures.

关键词： In-space production   LEO   Microgravity   Optical fibres   ZBLAN  

摘要： While satellite-based internet connectivity has been a recent hot topic, most of the global internet traffic passes through intercontinental Silica-based fibre-optic cables that span many thousands of kilometres. The unrelenting growth in demand for internet bandwidth and the need for redundancy means significantly more undersea cables are required [1]. Such cables, based on current silica-based fibres, are expensive to manufacture, to install, and to operate. Despite the transmission losses of Silica-based fibres being very low – ∼0.15 dB/km and very close to the intrinsic material loss of ∼0.12 dB/km – the signal strength after ∼100 km of propagation is very weak [2]. Multiple amplifiers are therefore embedded into the cables to repeatedly boost the signal, with each fibre requiring its own chain of dedicated amplifiers. Significant electrical power is also needed to power the amplifiers, adding to the cost [3].

关键词： AHRF   DUSP1   ERK 1/2   Tryptophan  

摘要： Acute hypoxemic respiratory failure (AHRF) presents considerable health hazards, as current prognostic instruments inadequately address its biochemical and inflammatory intricacies. The necessity for mechanistically informative biomarkers and targeted therapeutics is underscored. DUSP1 and ERK 1/2, essential for MAPK-mediated inflammatory signaling, may significantly influence the extent of lung injury and clinical outcomes in AHRF.

摘要： Deregulation of coagulation proteases can lead to a spectrum of hemostatic abnormalities, ranging from subtle subclinical to life-threatening coagulopathies. Additionally, coagulation factors play critical roles in many abnormalities beyond thrombosis, extending to hyperactive inflammatory responses and promoting tumorigenesis. Triple-negative breast cancers (TNBCs) are marked by a pro-thrombotic and highly inflammatory tumor microenvironment that fuels progression and therapeutic resistance, yet the molecular crosstalk linking coagulation signaling to inflammatory transcription remains incompletely understood. Here, we identify DNA topoisomerase I (Top1) as a critical downstream effector of thrombin-PAR1 driven inflammatory reprogramming in breast cancer cells. Thrombin enhances Top1 activity without altering its expression, amplifying NF-κB dependent cytokine production. Mechanistically, this response is governed by suppression of the tumor suppressor Par-4, which resides at the epicentre of this signaling axis and negatively regulates both Top1 and NF-κB. PAR1 activation enforces Par-4 loss through coordinated epigenetic silencing and phosphorylation-dependent cytoplasmic inactivation, thereby relieving transcriptional constraints and sustaining pro-tumorigenic inflammation. Importantly, targeting PAR1 markedly sensitizes TNBC tumors to the Top1 inhibitor irinotecan, highlighting a therapeutically actionable vulnerability. These findings reveal a previously unappreciated convergence of coagulation, epigenetic control, transcriptional activation and DNA topology control in breast cancer-suggesting the possibility of repurposing FDA-approved oral anticoagulants as an effective combinatorial therapy along with Top1 poisons in treating TNBCs.

关键词： Vitamin D3   25(OH)D3   1   25(OH)2D3   oral tissues   CYP27B1   antimicrobial peptides   inflammation  

摘要： Vitamin D₃ status profoundly affects oral health and disease. Over the last decade, evidence has emerged that vitamin D₃ activation can also occur in peripheral tissues. This narrative review was conducted to critically analyze the state of the art about the presence and activity of enzymes involved in the bioactivation of vitamin D₃ in the oral tissues.

关键词： Kinetic characterization   α subunit   Na   K+-ATPase   Hippocampus   Cerebral cortex   Enzymatic activity  

摘要：

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  All NKA isoforms showed biphasic curves for ATP in CX, but only α₁NKA did so in HP.
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  Na ⁺ affinity showed opposing regional patterns, α₁NKA being higher in CX than HP.
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  The α_2/3NKA isoforms displayed lower K⁺ affinity in CX compared with HP.
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  α₁NKA consistently exhibited higher Mg²⁺ affinity than α_2/3NKA in both brain regions.
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  NH₄⁺ affinity was higher in HP than CX across all NKA isoforms.