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关键词： Insulin sensitivity   Transforming growth factor beta 1 (TGFβ1)   Insulin receptor substrate 1 (IRS1)   Cullin 7 (CUL7)  

摘要： Obesity is associated with insulin resistance, a major risk factor for type 2 diabetes (T2D), yet the underlying mechanisms remain incompletely defined. We hypothesized that elevated transforming growth factor beta 1 (TGFβ1) level is associated with impaired insulin sensitivity.

关键词： Dictyostelium   Mitochondrial dynamics   Mitophagy   P62/SQSTM1   Redox homeostasis  

摘要： Sequestosome-1 (SQSTM1/p62) is a multifunctional scaffold protein that links autophagy, proteasomal degradation, and redox signalling, but its mitochondrial functions in lower eukaryotes remains unclear. Using p62 mutant strains of the protist, Dictyostelium discoideum, we demonstrate that p62 is a critical regulator of mitochondrial integrity and oxidative stress tolerance. Loss of p62 reduced cell survival during starvation and elevated oxidative stress, as evidenced by the increased proportion of DHE-positive cells, enhanced MitoSOX fluorescence, and nearly 40% reduction in mitochondrial membrane potential. Mitochondrial network analysis revealed a fragmented mitochondrial architecture in p62⁻ cells, consistent with a fission-dominated dynamics as quantified by live-cell time-lapse confocal microscopy. Overexpression of p62, restored redox balance, upregulated antioxidant enzyme activities (SOD and GST), and shifted mitochondrial dynamics towards fusion, resulting in mitochondrial elongation and network formation. Notably, p62⁻ cells were also characterised by increased basal and starvation-induced mitophagy that persisted despite canonical autophagy modulation, suggesting the involvement of a non-canonical, Atg8-independent mechanism. Collectively, these findings reveal a conserved role for p62 in governing mitochondrial quality control by modulating redox homeostasis and mitochondrial dynamics.

关键词： Core-shell structure   TS-1 zeolite   S-1 zeolite   Cobalt oxide   Ethylbenzene oxidation   Acetophenone  

摘要：

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  The core-shell structure CoOx/TS-1@S-1 was synthesized via a hydrothermal method.
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  The catalyst demonstrates excellent cycling stability and regeneration performance in the oxidation of ethylbenzene to acetophenone.
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  Reaction involves dual-path synergistic mechanism of radicals and carbocations.
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  Optimized conditions achieve 84.5% ethylbenzene conversion and 79.8% acetophenone.

关键词： Mammuthus primigenius   Late Gravettian   South-eastern Germany   Bavaria   Cut marks   Bones  

摘要：

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  Mammoth skeleton from SE Germany (26.9–25.3 ka cal BP) bears cut marks.
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  Few indications of human presence in Bavaria exist for this period.
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  Final Gravettian excursions into Bavaria before the LGM-related hiatus.

关键词： Electrodeposition   Ternery chalcogenides   CO2 reduction   Photoelectrochemical properties  

摘要：

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  Novel CdSSe films via room-temperature electrodeposition on nickel.
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  Comprehensive film characterization using XRD, EDX, and SEM.
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  Promising photoelectrochemical performance for CO₂ reduction.
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  Electronic properties analyzed with Mott-Schottky and impedance studies.

关键词： Alcoholic fatty liver disease   IGF-1   PPARG   Rosavin   p38 MAPK  

摘要： Rosavin, a characteristic component of Rhodiola rosea L., exhibits various pharmacological activities, including antioxidant and anti-inflammatory effects. However, its role in alcoholic fatty liver disease (AFLD) remains unclear. The aim of this study was to investigate the protective effects of Rosavin against AFLD and to elucidate its underlying molecular mechanisms. In this study, Rosavin (25 μM and 50 μM for in vitro; 100 and 200 mg/kg/d via oral gavage for 10 days in vivo) was found to significantly mitigate alcohol-induced hepatic lipid accumulation, enhance antioxidant capacity, and alleviate liver injury, demonstrating its protective effects against AFLD both in vitro and in vivo. Through network pharmacology and molecular docking, six potential targets of Rosavin in AFLD were identified: nitric oxide synthase 3 (NOS3), proto-oncogene tyrosine-protein kinase Src (SRC), peroxisome proliferator-activated receptor gamma (PPARG), mitogen-activated protein kinase 14 (MAPK14, also known as p38α), tumor necrosis factor alpha (TNFα), and insulin-like growth factor 1 (IGF-1). RT-qPCR and western blotting confirmed that Rosavin downregulates PPARG, TNFα, and IGF-1 expression and suppresses p38 phosphorylation. Rescue experiments further revealed that the suppressive effect of Rosavin on PPARG expression is reversed by the PPARG-specific agonist Mesalazine, which not only counteracts the protective effects of Rosavin but also reverses Rosavin-induced changes in MAPK14 and IGF-1 expression. In conclusion, Rosavin alleviates AFLD by downregulating PPARG and subsequently modulating the MAPK14 and IGF-1 signaling pathways. This study provides the first evidence that Rosavin protects against AFLD via PPARG, highlighting its potential as a therapeutic agent for AFLD treatment.

关键词： Acute lung injury   Fibroblast   IL-6   Oxidative phosphorylation   Single cell analysis  

摘要： Sepsis-induced acute lung injury (ALI) and early fibrotic remodeling remain major clinical challenges with limited effective treatments. In this study, we systematically investigated the role of fibroblasts in sepsis-associated lung injury and fibrosis using single-cell RNA sequencing combined with functional validation. We found that fibroblast states shifted from a resting state toward pro-inflammatory and pro-fibrotic phenotypes during sepsis, including Glycoprotein-producing Fibroblasts, Stress-activated Fibroblasts, and Inflammatory Fibroblasts, accompanied by increased IL-6 signaling activity. Mechanistically, IL-6/Signal Transducer and Activator of Transcription 3 (STAT3) signaling was associated with impaired mitochondrial oxidative phosphorylation (OXPHOS) in fibroblasts, increased mitochondrial ROS production, and increased activation of the AP-1 transcription factor family, which was linked to enhanced profibrotic protein expression. Pharmacological intervention with clinically relevant glucocorticoids, dexamethasone and methylprednisolone, attenuated lung injury and fibrosis in experimental sepsis-associated lung injury and was associated with suppression of the IL-6/STAT3/OXPHOS/AP-1 axis. Collectively, these findings highlight IL-6/STAT3-mediated mitochondrial metabolic remodeling in fibroblasts as a potential therapeutic target for sepsis-induced lung injury and fibrosis.

关键词： sup>28SiH4   Absolute line strengths   Dipole moment parameters   Hot bands  

摘要： Absolute line strengths of ²⁸SiH${}_4$ were measured for the first time with a Bruker Fourier transform infrared spectrometer IFS120HR and analyzed in the 1180–1360 cm⁻¹ region where the ${\nu }_1-{\nu }_4$, ${\nu }_3-{\nu }_4$, ${\nu }_3-{\nu }_2$ and ${\nu }_1-{\nu }_2$ ”hot“ bands of SiH${}_4$ are located. The strengths of 429 isolated nonsaturated and not too weak (i.e., which transmittances for the present experiment are

关键词： GLP-1 receptor agonist   Shoulder arthroplasty   Perioperative complications   Diabetes mellitus   Obesity   Sepsis  

摘要： Multiple studies in knee and hip arthroplasty populations have reported favorable perioperative complication profiles among patients receiving glucagon-like peptide-1 receptor agonists (GLP-1 RAs). However, evidence in shoulder arthroplasty remains conflicting, and no comprehensive review has evaluated their impact in this population. This study aimed to synthesize current evidence on the association between GLP-1 RA use and short- and mid-term perioperative complications following shoulder arthroplasty.

关键词： Alzheimer’s disease   amyloid-beta oligomers   amyloid precursor protein/presenilin 1   insulin receptor substrate 1   insulin resistance   metabolic reprogramming   molecular medicine   neuron   oxidative phosphorylation   pre-B-cell leukemia transcription factor 1  

摘要： Alzheimer's disease is characterized by hippocampal neuronal apoptosis,which leads to cognitive decline.The pathophysiology of Alzheimer's disease is largely driven by disrupted cellular metabolism and insufficient neuronal energy supply.However,current treatments for Alzheimer's disease remain limited because of side effects and disease complexity.Increasing evidence suggests that amyloid-βoligomer-induced neuronal insulin resistance and metabolic dysfunction play key roles in Alzheimer's disease progression,yet their underlying mechanisms and therapeutic strategies remain unclear.In this translational preclinical study,we combined a case-control analysis,in vitro cell assays,and in vivo experiments using amyloid precursor protein/presenilin 1 transgenic mice to investigate whether transcriptional regulation of key regulatory factors restores neuronal energy supply and improves Alzheimer's disease-induced pathology.The case-control analysis identified pre-B-cell leukemia transcription factor 1 as a crucial regulator of brain metabolic homeostasis in Alzheimer's disease.We developed a blood-brain barrier-permeable trans-activator of transcription-pre-B-cell leukemia transcription factor 1 fusion protein to enhance pre-B-cell leukemia transcription factor 1 expression,with the aim of restoring neuronal energy supply and reducing apoptosis.Mechanistic investigations using Alzheimer's disease models revealed that pre-B-cell leukemia transcription factor 1 transcriptionally upregulates insulin receptor substrate 1 by interacting with its promoter,which resulted in augmented insulin signaling.Trans-activator of transcription-pre-B-cell leukemia transcription factor 1 downregulated PDK4,significantly upregulated the expression of pyruvate dehydrogenase,and promoted mitochondrial oxidative phosphorylation activity,which inhibited the abnormally enhanced glycolytic flux,increased adenosine triphosphate production,and ultimately helped restore neuronal energy homeostasis.The