A Novel Dosimetry Method for Small Animal Irradiators Using 3D-printed Mouse Phantoms and Alanine Dosimeters.Christopher Duncan1,Chad Gunther1(1.C&C Irradiator Service,LLC,Washington,DC,20006.)Abstract:Accurate do...A Novel Dosimetry Method for Small Animal Irradiators Using 3D-printed Mouse Phantoms and Alanine Dosimeters.Christopher Duncan1,Chad Gunther1(1.C&C Irradiator Service,LLC,Washington,DC,20006.)Abstract:Accurate dosimetry is a crucial component of small animal and preclinical irradiation studies.展开更多
Osteoarthritis(OA) and rheumatoid arthritis(RA) have long been framed as degenerative and autoimmune entities, respectively;mounting evidence instead supports a unified mechano-immune paradigm in which joint loading a...Osteoarthritis(OA) and rheumatoid arthritis(RA) have long been framed as degenerative and autoimmune entities, respectively;mounting evidence instead supports a unified mechano-immune paradigm in which joint loading and inflammatory signaling are reciprocally reinforcing. In this review, we synthesize advances across mechanotransduction(Piezo1;YAP/TAZ), focaladhesion/cytoskeletal regulation(vinculin, filamin-A;upstream talin-1/Kindlin-2/paxillin), and niche inflammatory mediators(HE4, IL-36/IL-38) to explain how mechanical stress and cytokines co-produce persistent catabolism, synovial invasion, and fibrotic remodeling. We articulate a dual-hit model in which OA is predominantly mechanical-overload-driven, with secondary inflammation, whereas RA is immune-driven but imposes abnormal mechanical stress that further distorts joint biomechanics;both converge on canonical hubs(NF-κB/MAPK/JAK-STAT) to accelerate matrix degradation and apoptosis. Building on this framework, we propose integrated multi-marker panels that combine mechanosensors and adhesion proteins with conventional assays(CRP, ESR, anti-CCP) to enhance differential diagnosis and prognostication, particularly in postmenopausal women, where estrogen decline heightens mechano-immune susceptibility, thereby offering a means to quantify the impact of mechano-immune dysregulation. Integrating mechanotransductive and cytoskeletal biomarkers with conventional serological indices has been reported to improve differential diagnosis between osteoarthritis and rheumatoid arthritis in exploratory studies. While the magnitude of diagnostic gain varies across cohorts, combined biomarker strategies generally show enhanced discriminatory performance compared with single-marker approaches. These findings highlight translational potential but require validation in large, standardized clinical populations before routine implementation. Finally, we map translational opportunities spanning Piezo1 inhibition(GsMTx4), YAP/TAZ blockade(verteporfin), IL-36 axis antagonism(IL-36Ra, IL-38), anti-HE4 strategies for RA-ILD, and adhesion-stabilizing approaches, alongside mechanoresponsive biomaterials for regenerative applications and precision medicine guided by biomarker profiles. Collectively, this review reframes OA and RA as mechano-immune syndromes and delineates a clinically actionable roadmap from biophysics to bedside.展开更多
Astrocytes are implicated in the pathological changes of Alzheimer's disease.Our previous studies have demonstrated that estrogen deprivation and oxidative stress act synergistically to accelerate the progress of ...Astrocytes are implicated in the pathological changes of Alzheimer's disease.Our previous studies have demonstrated that estrogen deprivation and oxidative stress act synergistically to accelerate the progress of Alzheimer's disease.Long-term D-galactose injection combined with ovariectomy may serve as a rodent model for Alzheimer's disease.To address the potential contribution of astroglia to the Alzheimer's disease pathogenesis,we investigated pathological and biochemical alterations of astrocytes under this animal model.Ovadectomized rats injected with D-galactose for 2 weeks showed extensive localization of glial fibrillary acidic protein immunoreactive astrocytes and slightly elevated glutathione levels in the hippocampus without significant impairments in the water maze test and deficits of the cholinergic analyses,compared to the saline-injected rats.Ovariectomized rats injected with D-galactose for 6 weeks,however,exhibited degeneration of astrocytes and decreased glutathione levels in the hippocampus,accompanied with severe dysfunction of behavioral test and deficiency of cholinergic terminals.Electron microscopy further confirmed the pathological changes of astrocytes,especially in the aggregated area of synapse and brain microvessels.Consistent with degeneration of perivascular astrocytic endfeet,analysis of the horseradish peroxidase demonstrated an impairment of the blood-brain barrier permeability.These findings indicate that biochemical and pathological alterations of astrocytes may partially contribute to exacerbating neuronal deficits in the course of Alzheimer's disease.Restoring neuroprotective potential of astrocytes may be a useful therapeutic target for Alzheimer's disease and other neurodegenerative diseases.展开更多
This study investigated the expression characteristics and clinical significance of gamma-aminobutyric acid A(GABAA)receptor subunit gamma1(GABRG1)in glioma by integrating cancer and normal tissue data from multiple d...This study investigated the expression characteristics and clinical significance of gamma-aminobutyric acid A(GABAA)receptor subunit gamma1(GABRG1)in glioma by integrating cancer and normal tissue data from multiple databases and combining them with experimental evidence.The research revealed that GABRG1 exhibited low expression levels in glioma,and its low expression was closely associated with unfavorable clinical outcomes.Furthermore,a prognostic model with strong decision-making ability was constructed using multivariate Cox regression analysis,incorporating age,isocitric dehydrogenase(IDH)mutation status,O6-methylguanine-DNA methyltransferase(MGMT)methylation status,World Health Organization(WHO)grade,and GABRG1 expression.Additionally,GABRG1 might be associated with the expression of tumor-associated macrophages and was significantly linked to immune regulatory processes.This study provided a new target for immunotherapy in glioma and offered a novel indicator for predicting and evaluating the clinical prognosis of patients.展开更多
文摘A Novel Dosimetry Method for Small Animal Irradiators Using 3D-printed Mouse Phantoms and Alanine Dosimeters.Christopher Duncan1,Chad Gunther1(1.C&C Irradiator Service,LLC,Washington,DC,20006.)Abstract:Accurate dosimetry is a crucial component of small animal and preclinical irradiation studies.
文摘Osteoarthritis(OA) and rheumatoid arthritis(RA) have long been framed as degenerative and autoimmune entities, respectively;mounting evidence instead supports a unified mechano-immune paradigm in which joint loading and inflammatory signaling are reciprocally reinforcing. In this review, we synthesize advances across mechanotransduction(Piezo1;YAP/TAZ), focaladhesion/cytoskeletal regulation(vinculin, filamin-A;upstream talin-1/Kindlin-2/paxillin), and niche inflammatory mediators(HE4, IL-36/IL-38) to explain how mechanical stress and cytokines co-produce persistent catabolism, synovial invasion, and fibrotic remodeling. We articulate a dual-hit model in which OA is predominantly mechanical-overload-driven, with secondary inflammation, whereas RA is immune-driven but imposes abnormal mechanical stress that further distorts joint biomechanics;both converge on canonical hubs(NF-κB/MAPK/JAK-STAT) to accelerate matrix degradation and apoptosis. Building on this framework, we propose integrated multi-marker panels that combine mechanosensors and adhesion proteins with conventional assays(CRP, ESR, anti-CCP) to enhance differential diagnosis and prognostication, particularly in postmenopausal women, where estrogen decline heightens mechano-immune susceptibility, thereby offering a means to quantify the impact of mechano-immune dysregulation. Integrating mechanotransductive and cytoskeletal biomarkers with conventional serological indices has been reported to improve differential diagnosis between osteoarthritis and rheumatoid arthritis in exploratory studies. While the magnitude of diagnostic gain varies across cohorts, combined biomarker strategies generally show enhanced discriminatory performance compared with single-marker approaches. These findings highlight translational potential but require validation in large, standardized clinical populations before routine implementation. Finally, we map translational opportunities spanning Piezo1 inhibition(GsMTx4), YAP/TAZ blockade(verteporfin), IL-36 axis antagonism(IL-36Ra, IL-38), anti-HE4 strategies for RA-ILD, and adhesion-stabilizing approaches, alongside mechanoresponsive biomaterials for regenerative applications and precision medicine guided by biomarker profiles. Collectively, this review reframes OA and RA as mechano-immune syndromes and delineates a clinically actionable roadmap from biophysics to bedside.
文摘Astrocytes are implicated in the pathological changes of Alzheimer's disease.Our previous studies have demonstrated that estrogen deprivation and oxidative stress act synergistically to accelerate the progress of Alzheimer's disease.Long-term D-galactose injection combined with ovariectomy may serve as a rodent model for Alzheimer's disease.To address the potential contribution of astroglia to the Alzheimer's disease pathogenesis,we investigated pathological and biochemical alterations of astrocytes under this animal model.Ovadectomized rats injected with D-galactose for 2 weeks showed extensive localization of glial fibrillary acidic protein immunoreactive astrocytes and slightly elevated glutathione levels in the hippocampus without significant impairments in the water maze test and deficits of the cholinergic analyses,compared to the saline-injected rats.Ovariectomized rats injected with D-galactose for 6 weeks,however,exhibited degeneration of astrocytes and decreased glutathione levels in the hippocampus,accompanied with severe dysfunction of behavioral test and deficiency of cholinergic terminals.Electron microscopy further confirmed the pathological changes of astrocytes,especially in the aggregated area of synapse and brain microvessels.Consistent with degeneration of perivascular astrocytic endfeet,analysis of the horseradish peroxidase demonstrated an impairment of the blood-brain barrier permeability.These findings indicate that biochemical and pathological alterations of astrocytes may partially contribute to exacerbating neuronal deficits in the course of Alzheimer's disease.Restoring neuroprotective potential of astrocytes may be a useful therapeutic target for Alzheimer's disease and other neurodegenerative diseases.
基金Supported by the National Natural Science Foundation of China(82271340,82071368)the Outstanding Youth Funding of Harbin Medical University(HYD2020JQ0016)the Horizontal Subject(86010900)。
文摘This study investigated the expression characteristics and clinical significance of gamma-aminobutyric acid A(GABAA)receptor subunit gamma1(GABRG1)in glioma by integrating cancer and normal tissue data from multiple databases and combining them with experimental evidence.The research revealed that GABRG1 exhibited low expression levels in glioma,and its low expression was closely associated with unfavorable clinical outcomes.Furthermore,a prognostic model with strong decision-making ability was constructed using multivariate Cox regression analysis,incorporating age,isocitric dehydrogenase(IDH)mutation status,O6-methylguanine-DNA methyltransferase(MGMT)methylation status,World Health Organization(WHO)grade,and GABRG1 expression.Additionally,GABRG1 might be associated with the expression of tumor-associated macrophages and was significantly linked to immune regulatory processes.This study provided a new target for immunotherapy in glioma and offered a novel indicator for predicting and evaluating the clinical prognosis of patients.
