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1.
Immunity ; 55(7): 1185-1199.e8, 2022 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-35738281

RESUMEN

Lipoprotein disorder is a common feature of chronic pancreatitis (CP); however, the relationship between lipoprotein disorder and pancreatic fibrotic environment is unclear. Here, we investigated the occurrence and mechanism of pancreatic stellate cell (PSC) activation by lipoprotein metabolites and the subsequent regulation of type 2 immune responses, as well as the driving force of fibrotic aggressiveness in CP. Single-cell RNA sequencing revealed the heterogeneity of PSCs and identified very-low-density lipoprotein receptor (VLDLR)+ PSCs that were characterized by a higher lipid metabolism. VLDLR promoted intracellular lipid accumulation, followed by interleukin-33 (IL-33) expression and release in PSCs. PSC-derived IL-33 strongly induced pancreatic group 2 innate lymphoid cells (ILC2s) to trigger a type 2 immune response accompanied by the activation of PSCs, eventually leading to fibrosis during pancreatitis. Our findings indicate that VLDLR-enhanced lipoprotein metabolism in PSCs promotes pancreatic fibrosis and highlight a dominant role of IL-33 in this pro-fibrotic cascade.


Asunto(s)
Células Estrelladas Pancreáticas , Pancreatitis Crónica , Receptores de LDL/metabolismo , Células Cultivadas , Fibrosis , Humanos , Inmunidad Innata , Interleucina-33/metabolismo , Metabolismo de los Lípidos , Lipoproteínas VLDL/metabolismo , Linfocitos/metabolismo , Páncreas/patología , Células Estrelladas Pancreáticas/metabolismo , Células Estrelladas Pancreáticas/patología , Pancreatitis Crónica/metabolismo , Pancreatitis Crónica/patología
2.
Stem Cells ; 42(4): 360-373, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38153253

RESUMEN

Recent investigations have shown that the necroptosis of tissue cells in joints is important in the development of osteoarthritis (OA). This study aimed to investigate the potential effects of exogenous skeletal stem cells (SSCs) on the necroptosis of subchondral osteoblasts in OA. Human SSCs and subchondral osteoblasts isolated from human tibia plateaus were used for Western blotting, real-time PCR, RNA sequencing, gene editing, and necroptosis detection assays. In addition, the rat anterior cruciate ligament transection OA model was used to evaluate the effects of SSCs on osteoblast necroptosis in vivo. The micro-CT and pathological data showed that intra-articular injections of SSCs significantly improved the microarchitecture of subchondral trabecular bones in OA rats. Additionally, SSCs inhibited the necroptosis of subchondral osteoblasts in OA rats and necroptotic cell models. The results of bulk RNA sequencing of SSCs stimulated or not by tumor necrosis factor α suggested a correlation of SSCs-derived tumor necrosis factor α-induced protein 3 (TNFAIP3) and cell necroptosis. Furthermore, TNFAIP3-derived from SSCs contributed to the inhibition of the subchondral osteoblast necroptosis in vivo and in vitro. Moreover, the intra-articular injections of TNFAIP3-overexpressing SSCs further improved the subchondral trabecular bone remodeling of OA rats. Thus, we report that TNFAIP3 from SSCs contributed to the suppression of the subchondral osteoblast necroptosis, which suggests that necroptotic subchondral osteoblasts in joints may be possible targets to treat OA by stem cell therapy.


Asunto(s)
Osteoartritis , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa , Animales , Humanos , Ratas , Necroptosis , Osteoartritis/metabolismo , Osteoartritis/patología , Osteoartritis/terapia , Osteoblastos/metabolismo , Osteoblastos/patología , Células Madre/metabolismo , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/metabolismo , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/farmacología
3.
Cereb Cortex ; 34(1)2024 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-37997466

RESUMEN

Blood proteins are emerging as potential biomarkers for mild traumatic brain injury (mTBI). Molecular pathology of mTBI underscores the critical roles of neuronal injury, neuroinflammation, and vascular health in disease progression. However, the temporal profile of blood biomarkers associated with the aforementioned molecular pathology after CT-negative mTBI, their diagnostic and prognostic potential, and their utility in monitoring white matter integrity and progressive brain atrophy remain unclear. Thus, we investigated serum biomarkers and neuroimaging in a longitudinal cohort, including 103 CT-negative mTBI patients and 66 matched healthy controls (HCs). Angiogenic biomarker vascular endothelial growth factor (VEGF) exhibited the highest area under the curve of 0.88 in identifying patients from HCs. Inflammatory biomarker interleukin-1ß and neuronal cell body injury biomarker ubiquitin carboxyl-terminal hydrolase L1 were elevated in acute-stage patients and associated with deterioration of cognitive function from acute-stage to 6-12 mo post-injury period. Notably, axonal injury biomarker neurofilament light (NfL) was elevated in acute-stage patients, with higher levels associated with impaired white matter integrity in acute-stage and progressive gray and white matter atrophy from 3- to 6-12 mo post-injury period. Collectively, our findings emphasized the potential clinical value of serum biomarkers, particularly NfL and VEGF, in diagnosing mTBI and monitoring disease progression.


Asunto(s)
Conmoción Encefálica , Humanos , Conmoción Encefálica/diagnóstico por imagen , Factor A de Crecimiento Endotelial Vascular , Proteínas de Neurofilamentos , Progresión de la Enfermedad , Biomarcadores , Atrofia/patología , Tomografía Computarizada por Rayos X , Encéfalo/diagnóstico por imagen , Encéfalo/patología
4.
Small ; 20(12): e2306991, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37939298

RESUMEN

The shuttle effect, which causes the loss of active sulfur, passivation of lithium anode, and leads to severe capacity attenuation, is currently the main bottleneck for lithium-sulfur batteries. Recent studies have disclosed that molybdenum compounds possess exceptional advantages as a polar substrate to immobilize and catalyze lithium polysulfide such as high conductivity and strong sulfiphilicity. However, these materials show incomplete contact with sulfur/polysulfides, which causes uneven redox conversion of sulfur and results in poor rate performance. Herein, a new type of 2D nano-channeled molybdenum compounds (2D-MoNx) via the 2D organic-polyoxometalate superstructure for accelerating interfacial polysulfide catalysis toward high-performance lithium-sulfur batteries is reported. The 2D-MoNx shows well-interlinked nano-channels, which increase the reactive interface and contact surface with polysulfides. Therefore, the battery equipped with 2D-MoNx displays a high discharge capacity of 912.7 mAh g-1 at 1 C and the highest capacity retention of 523.7 mAh g-1 after 300 cycles. Even at the rate of 2 C, the capacity retention can be maintained at 526.6 mAh g-1 after 300 cycles. This innovative nano-channel and interfacial design of 2D-MoNx provides new nanostructures to optimize the sulfur redox chemistry and eliminate the shuttle effect of polysulfides.

5.
J Virol ; 97(5): e0177022, 2023 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-37129496

RESUMEN

Vimentin (VIM), an indispensable protein, is responsible for the formation of intermediate filament structures within cells and plays a crucial role in viral infections. However, the precise role of VIM in classical swine fever virus (CSFV) infection remains unclear. Herein, we systematically investigated the function of VIM in CSFV replication. We demonstrated that both knockdown and overexpression of VIM affected CSFV replication. Furthermore, we observed by confocal microscopy the rearrangement of cellular VIM into a cage-like structure during CSFV infection. Three-dimensional (3D) imaging indicated that the cage-like structures were localized in the endoplasmic reticulum (ER) and ringed around the double-stranded RNA (dsRNA), thereby suggesting that VIM was associated with the formation of the viral replication complex (VRC). Mechanistically, phosphorylation of VIM at serine 72 (Ser72), regulated by the RhoA/ROCK signaling pathway, induced VIM rearrangement upon CSFV infection. Confocal microscopy and coimmunoprecipitation assays revealed that VIM colocalized and interacted with CSFV NS5A. Structurally, it was determined that amino acids 96 to 407 of VIM and amino acids 251 to 416 of NS5A were the respective important domains for this interaction. Importantly, both VIM knockdown and disruption of VIM rearrangement inhibited the localization of NS5A in the ER, implying that VIM rearrangement recruited NS5A to the ER for VRC formation. Collectively, our results suggest that VIM recruits NS5A to form a stable VRC that is protected by the cage-like structure formed by VIM rearrangement, ultimately leading to enhanced virus replication. These findings highlight the critical role of VIM in the formation and stabilization of VRC, which provides alternative strategies for the development of antiviral drugs. IMPORTANCE Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is a highly infectious disease that poses a significant threat to the global pig industry. Therefore, gaining insights into the virus and its interaction with host cells is crucial for developing effective antiviral measures and controlling the spread of CSF. Previous studies have shown that CSFV infection induces rearrangement of the endoplasmic reticulum, leading to the formation of small vesicular organelles containing nonstructural protein and double-stranded RNA of CSFV, as well as some host factors. These organelles then assemble into viral replication complexes (VRCs). In this study, we have discovered that VIM recruited CSFV NS5A to form a stable VRC that was protected by a cage-like structure formed by rearranged VIM. This enhanced viral replication. Our findings not only shed light on the molecular mechanism of CSFV replication but also offer new insights into the development of antiviral strategies for controlling CSFV.


Asunto(s)
Virus de la Fiebre Porcina Clásica , Peste Porcina Clásica , Porcinos , Animales , Virus de la Fiebre Porcina Clásica/fisiología , Vimentina/metabolismo , ARN Bicatenario , Filamentos Intermedios/metabolismo , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo , Replicación Viral , Antivirales , Aminoácidos/genética
6.
Cell Commun Signal ; 22(1): 74, 2024 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-38279145

RESUMEN

The tumor microenvironment (TME) constitutes a complex microenvironment comprising a diverse array of immune cells and stromal components. Within this intricate context, tumor-associated macrophages (TAMs) exhibit notable spatial heterogeneity. This heterogeneity contributes to various facets of tumor behavior, including immune response modulation, angiogenesis, tissue remodeling, and metastatic potential. This review summarizes the spatial distribution of macrophages in both the physiological environment and the TME. Moreover, this paper explores the intricate interactions between TAMs and diverse immune cell populations (T cells, dendritic cells, neutrophils, natural killer cells, and other immune cells) within the TME. These bidirectional exchanges form a complex network of immune interactions that influence tumor immune surveillance and evasion strategies. Investigating TAM heterogeneity and its intricate interactions with different immune cell populations offers potential avenues for therapeutic interventions. Additionally, this paper discusses therapeutic strategies targeting macrophages, aiming to uncover novel approaches for immunotherapy. Video Abstract.


Asunto(s)
Neoplasias , Microambiente Tumoral , Humanos , Macrófagos , Macrófagos Asociados a Tumores , Inmunoterapia , Células Asesinas Naturales
7.
Eur Radiol ; 34(8): 5464-5476, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38276982

RESUMEN

OBJECTIVES: To preoperatively evaluate the human epidermal growth factor 2 (HER2) status in breast cancer using mammographic radiomics features and clinical characteristics on a multi-vendor and multi-center basis. METHODS: This multi-center study included a cohort of 1512 Chinese female with invasive ductal carcinoma of no special type (IDC-NST) from two different hospitals and five devices (1332 from Institution A, used for training and testing the models, and 180 women from Institution B, as the external validation cohort). The Gradient Boosting Machine (GBM) was employed to establish radiomics and multiomics models. Model efficacy was evaluated by the area under the curve (AUC). RESULTS: The number of HER2-positive patients in the training, testing, and external validation cohort were 245(26.3%), 105 (26.3.8%), and 51(28.3%), respectively, with no statistical differences among the three cohorts (p = 0.842, chi-square test). The radiomics model, based solely on the radiomics features, achieved an AUC of 0.814 (95% CI, 0.784-0.844) in the training cohort, 0.776 (95% CI, 0.727-0.825) in the testing cohort, and 0.702 (95% CI, 0.614-0.790) in the external validation cohort. The multiomics model, incorporated radiomics features with clinical characteristics, consistently outperformed the radiomics model with AUC values of 0.838 (95% CI, 0.810-0.866) in the training cohort, 0.788 (95% CI, 0.741-0.835) in the testing cohort, and 0.722 (95% CI, 0.637-0.811) in the external validation cohort. CONCLUSIONS: Our study demonstrates that a model based on radiomics features and clinical characteristics has the potential to accurately predict HER2 status of breast cancer patients across multiple devices and centers. CLINICAL RELEVANCE STATEMENT: By predicting the HER2 status of breast cancer reliably, the presented model built upon radiomics features and clinical characteristics on a multi-vendor and multi-center basis can help in bolstering the model's applicability and generalizability in real-world clinical scenarios. KEY POINTS: • The mammographic presentation of breast cancer is closely associated with the status of human epidermal growth factor receptor 2 (HER2). • The radiomics model, based solely on radiomics features, exhibits sub-optimal performance in the external validation cohort. • By combining radiomics features and clinical characteristics, the multiomics model can improve the prediction ability in external data.


Asunto(s)
Neoplasias de la Mama , Mamografía , Receptor ErbB-2 , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Receptor ErbB-2/metabolismo , Persona de Mediana Edad , Mamografía/métodos , Adulto , Anciano , Carcinoma Ductal de Mama/diagnóstico por imagen , Radiómica
8.
J Phys Chem A ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38954640

RESUMEN

Machine learning is capable of effectively predicting the potential energies of molecules in the presence of high-quality data sets. Its application in the construction of ground- and excited-state potential energy surfaces is attractive to accelerate nonadiabatic molecular dynamics simulations of photochemical reactions. Because of the huge computational cost of excited-state electronic structure calculations, the construction of a high-quality data set becomes a bottleneck. In the present work, we first built two data sets. One was obtained from surface hopping dynamics simulations at the semiempirical OM2/MRCI level. Another was extracted from the dynamics trajectories at the CASSCF level, which was reported previously. The ground- and excited-state potential energy surfaces of ethylene-bridged azobenzene at the CASSCF computational level were constructed based on the former low-level data set. Although non-neural network machine learning methods can achieve good or modest performance during the training process, only neural network models provide reliable predictions on the latter external test data set. The BPNN and SchNet combined with the Δ-ML scheme and the force term in the loss functions are recommended for dynamics simulations. Then, we performed excited-state dynamics simulations of the photoisomerization of ethylene-bridged azobenzene on machine learning potential energy surfaces. Compared with the lifetimes of the first excited state (S1) estimated at different computational levels, our results on the E isomer are in good agreement with the high-level estimation. However, the overestimation of the Z isomer is unimproved. It suggests that smaller errors during the training process do not necessarily translate to more accurate predictions on high-level potential energies or better performance on nonadiabatic dynamics simulations, at least in the present case.

9.
Cereb Cortex ; 33(12): 7477-7488, 2023 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-36928310

RESUMEN

Mild traumatic brain injury (mTBI) disrupts the integrity of white matter microstructure, which affects brain functional connectivity supporting cognitive function. Although the relationship between structural and functional connectivity (SC and FC), here called SC-FC coupling, has been studied on global level in brain disorders, the long-term disruption of SC-FC coupling in mTBI at regional scale was still unclear. The current study investigated the alteration pattern of regional SC-FC coupling in 104 acute mTBI patients (41 with 6-12 months of follow-up) and 56 healthy controls (HCs). SC and FC networks were constructed to measure regional, intra-network, and inter-network SC-FC coupling. Compared with HCs, acute mTBI exhibited altered SC-FC coupling of the sensorimotor network (SMN). The coupling laterality indicators of the SMN can identify mTBI from controls. The persistent SC-FC decoupling of the SMN and the additional decoupling of the default mode network (DMN) were observed in chronic mTBI. Crucially, decoupling of the SMN and DMN predicted better cognitive outcomes. The findings revealed the SC-FC coupling alternations exhibited hierarchical trend originating from the sensorimotor cortex to high-order cognitive regions with the progression of mTBI. The regional and hierarchical SC-FC coupling may be a prognostic biomarker to provide insights into the pathophysiology mechanism of mTBI.


Asunto(s)
Conmoción Encefálica , Disfunción Cognitiva , Humanos , Conmoción Encefálica/complicaciones , Conmoción Encefálica/diagnóstico por imagen , Imagen por Resonancia Magnética , Red Nerviosa/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Mapeo Encefálico
10.
Cereb Cortex ; 33(11): 6620-6632, 2023 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-36610729

RESUMEN

Traumatic brain injury (TBI) disrupt the coordinated activity of triple-network and produce impairments across several cognitive domains. The triple-network model posits a key role of the salience network (SN) that regulates interactions with the central executive network (CEN) and default mode network (DMN). However, the aberrant dynamic interactions among triple-network and associations with neurobehavioral symptoms in mild TBI was still unclear. In present study, we used brain network interaction index (NII) and dynamic functional connectivity to examine the time-varying cross-network interactions among the triple-network in 109 acute patients, 41 chronic patients, and 65 healthy controls. Dynamic cross-network interactions were significantly increased and more variable in mild TBI compared to controls. Crucially, mild TBI exhibited an increased NII as enhanced integrations between the SN and CEN while reduced coupling of the SN with DMN. The increased NII also implied much severer and multiple domains of cognitive impairments at both acute and chronic mild TBI. Abnormities in time-varying engagement of triple-network is a clinically relevant neurobiological signature of psychopathology in mild TBI. The findings provided align with and advance an emerging perspective on the importance of aberrant brain dynamics associated with highly disparate cognitive and behavioral outcomes in trauma.


Asunto(s)
Conmoción Encefálica , Disfunción Cognitiva , Humanos , Conmoción Encefálica/complicaciones , Conmoción Encefálica/diagnóstico por imagen , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Red Nerviosa , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Disfunción Cognitiva/patología
11.
BMC Nephrol ; 25(1): 61, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38383316

RESUMEN

Fabry disease (FD) is an uncommon, X-linked, lysosomal storage disease that causes defects in the glycosphingolipid metabolic pathway due to deficient or absent lysosomal α-galactosidase (α-Gal A) activity. This leads to the accumulation of globotriaosylceramide (GL-3) within lysosomes in a wide range of cells, including endothelial, cardiac, renal, and corneal cells, and consequently, the progressive appearance of clinical symptoms in target organs. Enzyme replacement therapy (ERT), which involves the exogenous supplementation of α-Gal A enzyme and has been successfully administered for treating FD.Here, we report a case of a 37-year-old male with complaints of recurrent proteinuria and ventricular septal thickening. A renal biopsy revealed vacuolization and foamy changes in podocytes, and the presence of myelin-like bodies and zebra bodies. The white blood cell α-Gal A activity was very low, while the Lyso-GL-3 level was high. Additionally, genetic analysis revealed a gene variant c.902G > A p. Arg301Gln. The patient was diagnosed with FD, and subsequently received intravenous ERT with a dose of Agalsidase α (0.2 mg/kg, 17.5 mg every 2 weeks). Currently, the values of proteinuria and ventricular septum thickness remain stable during the 6-month follow-up. Initiating ERT at an early age can effectively decrease the deposition of GL-3, attenuate the progressive clinical manifestations of FD, and provide greater long-term benefits.


Asunto(s)
Enfermedad de Fabry , Masculino , Humanos , Adulto , Enfermedad de Fabry/complicaciones , Enfermedad de Fabry/tratamiento farmacológico , Enfermedad de Fabry/genética , Terapia de Reemplazo Enzimático , alfa-Galactosidasa/genética , alfa-Galactosidasa/uso terapéutico , Proteinuria/tratamiento farmacológico , Proteinuria/etiología , Riñón/patología , Ventrículos Cardíacos/patología
12.
Metab Brain Dis ; 39(5): 741-752, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38833094

RESUMEN

Apoptosis is the crucial pathological mechanism following cerebral ischemic injury. Our previous studies demonstrated that clonidine, one agonist of alpha2-adrenergic receptor (α2-AR), could attenuate cerebral ischemic injury in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). However, it's unclear whether clonidine exerts neuroprotective effects by regulating neuronal apoptosis. In this study, we elucidated whether clonidine can exert anti-apoptotic effects in cerebral ischemic injury, and further explored the possible mechanisms. Neurological deficit score was measured to evaluate the neurological function. TTC staining was used for the measurement of brain infarct size. Hematoxylin-Eosin (HE) staining was applied to examine the cell morphology. TUNEL and DAPI fluorescent staining methods were used to analyze the cell apoptosis in brain tissue. Fluorescence quantitative real-time PCR was performed to assess the gene expression of Caspase-3 and P53. Western blotting assay was applied to detect the protein expression of Caspase-3 and P53. The results showed that clonidine improved neurological function, reduced brain infarct size, alleviated neuronal damage, and reduced the ratio of cell apoptosis in the brain with MCAO/R injury. moreover, clonidine down-regulated the gene and protein expression of Caspase-3 and P53 which were over-expressed after MCAO/R injury. Whereas, yohimbine (one selective α2-AR antagonist) mitigated the anti-apoptosis effects of clonidine, accompanied by reversed gene and protein expression changes. The results indicated that clonidine attenuated cerebral MCAO/R injury via suppressing neuronal apoptosis, which may be mediated, at least in part, by activating α2-AR.


Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2 , Apoptosis , Clonidina , Neuronas , Fármacos Neuroprotectores , Ratas Sprague-Dawley , Daño por Reperfusión , Animales , Clonidina/farmacología , Clonidina/uso terapéutico , Apoptosis/efectos de los fármacos , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Masculino , Ratas , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/prevención & control , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Caspasa 3/metabolismo , Receptores Adrenérgicos alfa 2/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología
13.
Acta Radiol ; 65(3): 284-293, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38115811

RESUMEN

BACKGROUND: An applicable magnetic resonance imaging (MRI) biomarker for diffuse midline glioma (DMG), H3 K27-altered of the spinal cord is important for non-invasive diagnosis. PURPOSE: To evaluate the efficacy of conventional MRI (cMRI) in distinguishing between DMGs, H3 K27-altered, gliomas without H3 K27-alteration, and demyelinating lesions in the spinal cord. MATERIAL AND METHODS: Between January 2017 and February 2023, patients with pathology-confirmed spinal cord gliomas (including ependymomas) with definite H3 K27 status and demyelinating diseases diagnosed by recognized criteria were recruited as the training set for this retrospective study. Morphologic parameter assessment was performed by two neuroradiologists on T1-weighted, T2-weighted, and contrast-enhanced T1-weighted imaging. Variables with high inter- and intra-observer agreement were included in univariable correlation analysis and multivariable logistic regression. The performance of the final model was verified by internal and external testing sets. RESULTS: The training cohort included 21 patients with DMGs (13 men; mean age = 34.57 ± 13.489 years), 21 with wild-type gliomas (10 men; mean age = 46.76 ± 17.017 years), and 20 with demyelinating diseases (5 men; mean age = 49.50 ± 18.872 years). A significant difference was observed in MRI features, including cyst(s), hemorrhage, pial thickening with enhancement, and the maximum anteroposterior diameter of the spinal cord. The prediction model, integrating age, age2, and morphological characteristics, demonstrated good performance in the internal and external testing cohort (accuracy: 0.810 and 0.800, specificity: 0.810 and 0.720, sensitivity: 0.872 and 0.849, respectively). CONCLUSION: Based on cMRI, we developed a model with good performance for differentiating among DMGs, H3 K27-altered, wild-type glioma, and demyelinating lesions in the spinal cord.


Asunto(s)
Neoplasias Encefálicas , Enfermedades Desmielinizantes , Glioma , Masculino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Glioma/diagnóstico por imagen , Glioma/patología , Imagen por Resonancia Magnética/métodos , Médula Espinal/diagnóstico por imagen , Enfermedades Desmielinizantes/diagnóstico por imagen , Neoplasias Encefálicas/patología
14.
Tohoku J Exp Med ; 262(3): 191-199, 2024 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-38171724

RESUMEN

Treatment-resistant depression (TRD) poses significant therapeutic challenges despite available interventions. Escitalopram (ESC) is a highly selective antidepressant. This study aimed to compare ESC alone and ESC combined with modified electroconvulsive therapy (MECT) or high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) in TRD patients. Ninety participants were randomized into ESC alone, ESC + MECT, and ESC + HF-rTMS groups. Notable differences were observed in Hamilton Depression Rating Scale (HDRS-17) scores at 12 weeks among ESC (14.37), ESC + MECT (10.27), and ESC + HF-rTMS (10.77) groups (P = 0.006). In terms of overall quality of life (QoL) evaluated using the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) at 12 weeks, the ESC, ESC + MECT, and ESC + HF-rTMS groups scored 2, 3, and 3.5, respectively. ESC + MECT/HF-rTMS groups showed reduced depressive symptoms compared to the ESC group, accompanied by higher overall QoL scores and increased satisfaction with health. Patients receiving ESC + MECT demonstrated no significant alterations in short-term memory and orientation, as measured by the Montreal Cognitive Assessment (MoCA), before and after treatment. Moreover, a decline in language was observed compared to baseline (12 weeks: median 2, IQR 2-3; baseline: median 1, IQR 1-3; P = 0.022). The positive impact of ESC with HF-rTMS on cognitive function was evidenced by improvements in all domines MoCA.Combining ESC with MECT or HF-rTMS exhibited enhanced effectiveness in alleviating depressive symptoms and enhancing QoL compared to ESC monotherapy. Specifically, the ESC + HF-rTMS combination displayed potential as a comprehensive treatment strategy for TRD, addressing both emotional and cognitive aspects.


Asunto(s)
Trastorno Depresivo Mayor , Terapia Electroconvulsiva , Humanos , Estimulación Magnética Transcraneal , Escitalopram , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/tratamiento farmacológico , Depresión/terapia , Calidad de Vida , Cognición , Resultado del Tratamiento
15.
Ecotoxicol Environ Saf ; 275: 116238, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38518609

RESUMEN

BACKGROUND: Mounting evidence has demonstrated that high temperature was associated with adverse health outcomes, especially morbidity and mortality. Nonetheless, the impact of extreme high temperature on cognitive performance, which is the fundamental capacity for interpreting one's surroundings, decision-making, and acquiring new abilities, has not been thoroughly investigated. METHODS: We aimed to assess associations between extreme high temperature at different time scales and poor cognitive function. We used longitudinal survey data from the three waves of data from China Family Panel Study, providing an 8-year follow-up of 53,008 participants from China. We assessed temperature and extreme high temperature exposure for each participant based on the residential area and date of cognitive test. We defined the proportion of days/hours above 32 °C as the metric of the exposure to extreme high temperature. Then we used generalized additive model and difference-in-differences approach to explore the associations between extreme high temperature and cognitive function. RESULTS: Our results demonstrated that either acute exposure or long-term exposure to extreme high temperature was associated with cognitive decline. At hourly level, 0-1 hour acute exposure to extreme high temperature would induce -0.93 % (95 % CI: -1.46 %, -0.39 %) cognitive change. At annual level, 10 percentage point increase in the hours proportion exceeding 32 °C in the past two years induced -9.87 % (95 % CI: -13.99 %, -5.75 %) cognitive change. Furthermore, subgroup analyses indicated adaptation effect: for the same 10 percentage increase in hours proportion exceeding 32 °C, people in warmer areas had cognitive change of -6.41 % (-11.22 %, -1.61 %), compared with -15.30 % (-21.07 %, -9.53 %) for people in cool areas. CONCLUSION: Our results demonstrated that extreme high temperature was associated with reduced cognitive function at hourly, daily and annual levels, warning that people should take better measures to protect the cognitive function in the context of climate change.


Asunto(s)
Cognición , Frío , Humanos , Temperatura , China , Estaciones del Año , Calor
16.
Chem Biodivers ; 21(4): e202400002, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38411310

RESUMEN

Seven new polyketides including three chromone derivatives (1-3) and four linear ones incorporating a tetrahydrofuran ring (4-7), along with three known compounds (8-10), were obtained from the fermentation of an endophytic fungus (Chaetomium sp. UJN-EF006) isolated from the leaves of Vaccinium bracteatum. The structures of these fungal metabolites have been elucidated by spectroscopic means including MS, NMR and electronic circular dichroism. A preliminary anti-inflammatory screening with the lipopolysaccharide (LPS) induced RAW264.7 cell model revealed moderate NO production inhibitory activity for compounds 1 and 4. In addition, the expression of three LPS-induced inflammatory factors IL-6, iNOS and COX-2 was also blocked by 1 and 4.


Asunto(s)
Chaetomium , Policétidos , Vaccinium myrtillus , Chaetomium/química , Policétidos/química , Lipopolisacáridos/farmacología , Estructura Molecular
17.
Sensors (Basel) ; 24(8)2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38676251

RESUMEN

With the acceleration of urbanisation, urban areas are subject to the combined effects of the accumulation of various natural factors, such as changes in temperature leading to the thermal expansion or contraction of surface materials (rock, soil, etc.) and changes in precipitation and humidity leading to an increase in the self-weight of soil due to the infiltration of water along the cracks or pores in the ground. Therefore, the subsidence of urban areas has now become a serious geological disaster phenomenon. However, the use of traditional neural network prediction models has limitations when examining the causal relationships between time series surface deformation data and multiple influencing factors and when applying multiple influencing factors for predictive analyses. To this end, Sentinel-1A data from March 2017 to February 2023 were used as the data source in this paper, based on time series deformation data acquired using the small baseline subset interferometric synthetic aperture radar (SBAS-InSAR) technique. A sparrow search algorithm-convolutional neural network-long short-term memory (SSA-CNN-LSTM) neural network prediction model was built. The six factors of temperature, humidity, precipitation, and ground temperature at three different depths below the surface (5 cm, 10 cm, and 15 cm) were taken as the input of the model, and the surface deformation data were taken as the output of the neural network model. The correlation between the spatial and temporal evolution characteristics of the ground subsidence in urban areas and various influencing factors was analysed using grey correlation analysis, which proved that these six factors contribute to some extent to the deformation of the urban surface. The main urban area of Hohhot City, Inner Mongolia Autonomous Region, was used as the study area. In order to verify the efficacy of this neural network prediction model, the prediction effects of the multilayer perceptron (MLP), backpropagation (BP), and SSA-CNN-LSTM models were compared and analysed, with the values of the correlation coefficients of the feature points of A1, B1, and C1 being in the range of 0.92, 0.83, and 0.93, respectively. The results show that compared with the traditional MLP and BP neural network models, the SSA-CNN-LSTM model achieves a higher performance in predicting time series surface deformation data in urban areas, which provides new ideas and methods for this area of research.

18.
Sensors (Basel) ; 24(4)2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38400328

RESUMEN

As urban economies flourish and populations become increasingly concentrated, urban surface deformation has emerged as a critical factor in city planning that cannot be overlooked. Surface deformation in urban areas can lead to deformations in structural supports of infrastructure such as road bases and bridges, thereby posing a serious threat to public safety and creating significant safety hazards. Consequently, research focusing on the monitoring of urban surface deformation holds paramount importance. Interferometric synthetic aperture radar (InSAR), as an important means of earth observation, has all-day, wide-range, high-precision, etc., characteristics and is widely used in the field of surface deformation monitoring. However, traditional solitary InSAR techniques are limited in their application scenarios and computational characteristics. Additionally, the manual selection of ground control points (GCPs) is fraught with errors and uncertainties. Permanent scatterers (PS) can maintain high interferometric coherence in man-made building areas, and distributed scatterers (DS) usually show moderate coherence in areas with short vegetation; the combination of DS and PS solves the problem of manually selecting GCPs during track re-flattening and regrading, which affects the monitoring results. In this paper, 45 Sentinel-1B data from 16 February 2019 to 14 December 2021 are used as the data source in the urban area of Horqin District, Tongliao City, Inner Mongolia Autonomous Region, for example. A four-threshold (coherence coefficient threshold, FaSHPS adaptive threshold, amplitude divergence index threshold, and deformation velocity interval) GCPs point screening method for PS-DS, as well as a Small Baseline Subset-Permanent Scatterers-Distributed Scatterers-Interferometric Synthetic Aperture Radar (SBAS-PS-DS-InSAR) method for selecting PS and DS points as ground control points for orbit refinement and re-flattening, are proposed. The surface deformation results obtained using the Small Baseline Subset Interferometric Synthetic Aperture Radar (SBAS-InSAR) and the SBAS-PS-DS-InSAR proposed in this paper were comparatively analysed and verified. The maximum cumulative line-of-sight settlements were -90.78 mm and -83.68 mm, and the maximum cumulative uplifts are 74.94 mm and 97.56 mm, respectively; the maximum annual average line-of-sight settlements are -35.38 mm/y and -30.38 mm/y, and the maximum annual average uplifts are 25.27 mm/y and 27.92 mm/y. The results were evaluated and analysed in terms of correlation, mean absolute error (MAE), and root mean square error (RMSE). The deformation results of the two InSAR methods were evaluated and analysed in terms of correlation, MAE, and RMSE. The errors show that the Pearson correlation coefficients between the vertical settlement results obtained using the SBAS-PS-DS-InSAR method and the GPS monitoring results were closer to 1. The maximum MAE and RMSE were 13.7625 mm and 14.8004 mm, respectively, which are within the acceptable range; this confirms that the monitoring results of the SBAS-PS-DS-InSAR method were better than those of the original SBAS-InSAR method. SBAS-InSAR method, which is valid and reliable. The results show that the surface deformation results obtained using the SBAS-InSAR, SBAS-PS-DS-InSAR, and GPS methods have basically the same settlement locations, extents, distributions, and temporal and spatial settlement patterns. The deformation results obtained using these two InSAR methods correlate well with the GPS monitoring results, and the MAE and RMSE are within acceptable limits. By comparing the deformation information obtained using multiple methods, the surface deformation in urban areas can be better monitored and analysed, and it can also provide scientific references for urban municipal planning and disaster warning.

19.
Aesthet Surg J ; 44(2): 117-130, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-37418635

RESUMEN

BACKGROUND: The volume and position of the buccal fat pad (BFP) change with age, which manifests as a hollow midface. Previous studies showed that autologous fat grafting for BFP augmentation could effectively ameliorate midfacial hollowing. OBJECTIVES: The aim of this study was to introduce a modified fat grafting technique for female patients with midfacial hollowing to restore the volume of BFP, and to evaluate the safety and effectiveness of this approach. METHODS: Two cadavers were used for the dissection of the BFP and to demonstrate the surgical procedures. Forty-eight patients were treated for midfacial hollowing with the modified grafting strategy. The BFP was filled through a percutaneous zygomatic incision and an immediate amelioration in the hollow area was observed. Improvements were evaluated from measurements of the ogee line and ogee angle, FACE-Q questionnaires, and 3-party satisfaction ratings. Clinical profiles were reviewed and statistically analysed. RESULTS: The mean [standard deviation] ogee angle was 6.6° [1.9°] preoperatively and 3.9° [1.4°] postoperatively (average reduction, 2.7°). Patients' ogee lines were smoother postoperatively, with marked improvements in overall appearance, psychological well-being, and social confidence. Patients reported high satisfaction with decision-making and postoperative outcomes and felt 6.61 [2.21] years younger. Overall, 88%, 76%, and 83% of the cases were graded as good or excellent in improvement by surgeon, patient, and the third party, respectively. CONCLUSIONS: For age-dependent midfacial hollowing in female patients, the modified percutaneous grafting technique described here was safe and efficacious in restoring BFP volume. This technique produced a smoother ogee line and a natural, younger midfacial contour.


Asunto(s)
Ritidoplastia , Humanos , Femenino , Ritidoplastia/métodos , Rejuvenecimiento , Cara/cirugía , Encuestas y Cuestionarios , Tejido Adiposo/trasplante
20.
Angew Chem Int Ed Engl ; 63(25): e202404019, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38622071

RESUMEN

Accelerating sulfur conversion catalysis to alleviate the shuttle effect has become a novel paradigm for effective Li-S batteries. Although nitrogen-coordinated metal single-atom (M-N4) catalysts have been investigated, further optimizing its utilization rate and catalytic activities is urgently needed for practical applications. Inspired by the natural alveoli tissue with interconnected structure and well-distributed enzyme catalytic sites on the wall for the simultaneously fast diffusion and in situ catalytic conversion of substrates, here, we proposed the controllable synthesis of bioinspired carbon cathode with interconnected porous structure and asymmetric coordinated V-S1N3 sites for efficient and stable Li-S batteries. The enzyme-mimetic V-S1N3 shows asymmetric electronic distribution and high tunability, therefore enhancing in situ polysulfide conversion activities. Experimental and theoretical results reveal that the high charge asymmetry degree and large atom radius of S in V-S1N3 result in sloping adsorption for polysulfide, thereby exhibiting low thermodynamic energy barriers and long-range stability (0.076 % decay over 600 cycles).

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