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AIM: Non-invasive diagnostics for metabolic dysfunction-associated fatty liver disease (MAFLD) remain challenging. We aimed to identify novel key genes as non-invasive biomarkers for MAFLD, elucidate causal relationships between biomarkers and MAFLD and determine the role of immune cells as potential mediators. MATERIALS AND METHODS: Utilizing published transcriptome data of patients with biopsy-proven MAFLD, we applied linear models for microarray data, least absolute shrinkage and selector operation (LASSO) regressions and receiver operating characteristic (ROC) curve analyses to identify and validate biomarkers for MAFLD. Using the expression quantitative trait loci database and a cohort of 778 614 Europeans, we used Mendelian randomization to analyse the causal relationships between key biomarkers and MAFLD. Additionally, mediation analysis was performed to examine the involvement of 731 immunophenotypes in these relationships. RESULTS: We identified 31 differentially expressed genes, and LASSO regression showed three hub genes, IGFBP2, PEG10, and P4HA1, with area under the receiver operating characteristic (AUROC) curve of 0.807, 0.772 and 0.791, respectively, for identifying MAFLD. The model of these three genes had an AUROC of 0.959 and 0.800 in the development and validation data sets, respectively. This model was also validated using serum-based enzyme-linked immunosorbent assay data from MAFLD patients and control subjects (AUROC: 0.819, 95% confidence interval: 0.736-0.902). PEG10 was associated with an increased MAFLD risk (odds ratio = 1.106, p = 0.032) via inverse variance-weighted analysis, and about 30% of this risk was mediated by the percentage of CD11c + CD62L- monocytes. CONCLUSIONS: The MAFLD panels have good diagnostic accuracy, and the causal link between PEG10 and MAFLD was mediated by the percentage of CD11c + CD62L- monocytes.
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In neurological diseases, the regulation of autophagy plays a crucial role in their pathology, particularly the relationship between autophagy and hepatic encephalopathy (HE) which merits detailed investigation. Glycosphingolipids are abundant and broadly functional in the nervous system and are closely associated with autophagy. However, the specific link and mechanisms between glycosphingolipids and autophagy in HE remain unclear. This study aims to explore the impact of glycosphingolipid changes on the autophagy in HE and its potential mechanisms. Utilizing lectin microarrays, we observed elevated expression levels of α2-3 sialylated glycosphingolipid in the brain tissue of HBV transgenic mice and ammonia-induced astrocyte models, suggesting that the increase in α2-3 sialylated glycosphingolipid is related to HE. Further research revealed that the increased expression of α2-3 sialylated glycosphingolipid, mediated by ST3GAL2, affects autophagy by regulating the autophagy initiation complex Vps34-Beclin-1. In summary, our research not only comprehensively reveals the changes in brain glycosphingolipid during HBV-related HE but also elucidates the interactions and regulatory mechanisms between α2-3 sialylated glycosphingolipid and autophagy. This study provides a new perspective on understanding the pathogenesis of HE and offers novel theories and targets for future research and treatment strategies.
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Autofagia , Glicoesfingolípidos , Encefalopatía Hepática , Sialiltransferasas , Animales , Encefalopatía Hepática/metabolismo , Encefalopatía Hepática/patología , Ratones , Glicoesfingolípidos/metabolismo , Sialiltransferasas/metabolismo , Sialiltransferasas/genética , Ratones Transgénicos , Encéfalo/metabolismo , Encéfalo/patología , Humanos , beta-Galactosida alfa-2,3-Sialiltransferasa , Astrocitos/metabolismo , MasculinoRESUMEN
Background: Solid pseudopapillary neoplasms of the pancreas with hepatic metastases are infrequent and difficult to diagnose, and treatment is uncertain. Methods: A retrospective analysis of clinical data from patients with pancreatic solid pseudopapillary neoplasm (SPN) hepatic metastases who underwent surgery at the First Hospital of Jilin University from January 2005 to December 2021 was conducted. A total of 287 patients with SPN were included in the study, of which 8 (3%) developed liver metastases, all of whom were treated surgically and recovered well after surgery. The clinical presentation, imaging features, surgical treatment, histopathological examination, and postoperative follow-up data (mean 70 months; range 28-138 months) of the patients were recorded and analyzed. Clinical response strategies can be derived by reviewing previous studies on hepatic metastases of SPNs. Results: For resectable hepatic metastases from pancreatic solid pseudopapillary neoplasms, early surgery with total resection of the primary tumor and metastasis has shown great efficiency and is associated with patient good prognosis. In patients presenting unresectable hepatic metastases, aggressive tumor reduction surgery resulted in the alleviation of clinical symptoms and reduction of tumor burden while potentially achieving long-term survival. Conclusion: For hepatic metastases of SPNs, a preoperative liver tissue biopsy is beneficial for a definitive diagnosis. Surgery demonstrates excellent therapeutic efficacy and is considered the preferred curative treatment approach. This paper presents clinical experiences with SPN-related hepatic metastases at the Affiliated Hospital of Jilin University, which can be used to guide patient counseling in clinical practice.
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BACKGROUND: Investigating immune cell infiltration in the brain post-ischemia-reperfusion (I/R) injury is crucial for understanding and managing the resultant inflammatory responses. This study aims to unravel the role of the RPS27A-mediated PSMD12/NF-κB axis in controlling immune cell infiltration in the context of cerebral I/R injury. METHODS: To identify genes associated with cerebral I/R injury, high-throughput sequencing was employed. The potential downstream genes were further analyzed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses. For experimental models, primary microglia and neurons were extracted from the cortical tissues of mouse brains. An in vitro cerebral I/R injury model was established in microglia using the oxygen-glucose deprivation/reoxygenation (OGD/R) technique. In vivo models involved inducing cerebral I/R injury in mice through the middle cerebral artery occlusion (MCAO) method. These models were used to assess neurological function, immune cell infiltration, and inflammatory factor release. RESULTS: The study identified RPS27A as a key player in cerebral I/R injury, with PSMD12 likely acting as its downstream regulator. Silencing RPS27A in OGD/R-induced microglia decreased the release of inflammatory factors and reduced neuron apoptosis. Additionally, RPS27A silencing in cerebral cortex tissues mediated the PSMD12/NF-κB axis, resulting in decreased inflammatory factor release, reduced neutrophil infiltration, and improved cerebral injury outcomes in I/R-injured mice. CONCLUSION: RPS27A regulates the expression of the PSMD12/NF-κB signaling axis, leading to the induction of inflammatory factors in microglial cells, promoting immune cell infiltration in brain tissue, and exacerbating brain damage in I/R mice. This study introduces novel insights and theoretical foundations for the treatment of nerve damage caused by I/R, suggesting that targeting the RPS27A and downstream PSMD12/NF-κB signaling axis for drug development could represent a new direction in I/R therapy.
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FN-kappa B , Daño por Reperfusión , Proteínas Ribosómicas , Transducción de Señal , Animales , Daño por Reperfusión/metabolismo , Daño por Reperfusión/inmunología , Daño por Reperfusión/genética , Ratones , FN-kappa B/metabolismo , Proteínas Ribosómicas/metabolismo , Proteínas Ribosómicas/genética , Masculino , Modelos Animales de Enfermedad , Microglía/metabolismo , Microglía/inmunología , Isquemia Encefálica/metabolismo , Isquemia Encefálica/genética , Isquemia Encefálica/inmunología , Neuronas/metabolismo , Ratones Endogámicos C57BL , Mapas de Interacción de ProteínasRESUMEN
BACKGROUND: Observational studies have shown that cholelithiasis and cholecystectomy are associated with the risk of breast cancer (BC) and gynecological cancers, but whether these relationships are causal has not been established and remains controversial. METHODS: Our study began with a meta-analysis that synthesized data from prior observational studies to examine the association between cholelithiasis, cholecystectomy, and the risk of BC and gynecological cancers. Subsequently, a two-sample Mendelian randomization (MR) analysis was conducted utilizing genetic variant data to investigate the potential causal relationship between cholelithiasis, cholecystectomy, and the aforementioned cancers. RESULTS: The results of the meta-analysis demonstrated a significant association between cholecystectomy and the risk of BC (risk ratio [RR] = 1.04, 95% confidence interval [CI]: 1.01-1.06, p = 0.002) and endometrial cancer (EC) (RR = 1.26, 95% CI: 1.02-1.56, p = 0.031). Conversely, no significant association was observed between cholelithiasis and the risk of BC, EC, and ovarian cancer. The MR analysis revealed no discernible causal connection between cholelithiasis and overall BC (p = 0.053), as well as BC subtypes (including estrogen receptor-positive/negative). Similarly, there was no causal effect of cholecystectomy on BC risk (p = 0.399) and its subtypes. Furthermore, no causal associations were identified between cholelithiasis, cholecystectomy, and the risk of gynecological cancers (ovarian, endometrial, and cervical cancer [CC]) (all p > 0.05). CONCLUSION: This study does not support a causal link between cholelithiasis and cholecystectomy and an increased risk of female cancers such as breast, endometrial, ovarian, and CC.
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In order to study the energy absorption characteristics of the open-section thin-walled composite structures with different cross-sections, axial compression tests were carried out at loading speeds of 0.01 m/s, 0.1 m/s, and 1 m/s. Finite element models were built to predict the crushing response and energy absorption behaviors of these open-section structures. The effects of the cross-section's shape, cross-section aspect ratio, trigger mechanism, and loading speed on the energy absorption characteristics of the composite structures were analyzed. The results show that the average crushing loads of the hat-shaped and Ω-shaped open-section structures are 14.1% and 14.6% higher than those of C-shaped open-section structures, and the specific energy absorption (SEA) values are 14.3% and 14.8% higher than that of C-shaped open-section structures, respectively. For the C-shaped open-section structures, a 45° chamfer trigger is more effective in reducing the initial peak load, while a 15° steeple trigger is more appropriate for the hat-shaped open-section structures. The average crushing loads and SEA of C-shaped, hat-shaped, and Ω-shaped open-section structures are reduced when the loading speed is increased from 0.01 m/s to 1 m/s. The increase in loading speed leads to the splashing of debris and thus reduces the loading area and material utilization of open-section structures, leading to a decrease in energy absorption efficiency.
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In this work, a special multilayer structure consisting of polylactic acid (PLA) and a co-continuous PLA/polycaprolactone (PCL)/multiwalled carbon nanotube (MWCNT) (ALM) composite with a double-percolated conductive network was fabricated via layer-assembly coextrusion. It was revealed that PLA domains located at the layer interface could serve as rivets properly linking adjacent layers. Such a nacre-like structure with alternately stacked rigid PLA and flexible ALM increased the fracture strain to 354.4%, nearly quadruple that of the PLA/PCL/MWCNT conventional blending composite with the same composition, while maintaining an excellent strength above 46.0 MPa. In addition, the multilayer composites showed a special frequency-selective electromagnetic interference (EMI) shielding performance, with tunable shielding peak positions controlled by the layer number. Their maximum EMI shielding effectiveness almost contributed by absorption loss could reach 49.8 dB, which originated from two aspects: one was the high electrical conductivity offered by the double-percolated distribution of MWCNTs, and the other was the multiple wave attenuation effect that occurred at the interfaces between PLA and ALM layers and the blend interfaces in ALM layers. This effort paves a new way for developing composites with outstanding mechanical and EMI shielding properties that can be extended to other polymeric composite systems.
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BACKGROUND: Arteriosclerosis obliterans (ASO) is a chronic arterial disease that can lead to critical limb ischemia. Endovascular therapy is increasingly used for limb salvage in ASO patients, but the outcomes vary. The development of prediction models using unsupervised machine learning may lead to the identification of novel subtypes to guide patient prognosis and treatment. METHODS: This retrospective study analyzed clinical data from 448 patients with ASOs who underwent endovascular therapy. Unsupervised machine learning algorithms were employed to identify subgroups. To validate the precision of the clustering outcomes, an analysis of the postoperative results of the clusters was conducted. A prediction model was constructed using binary logistic regression. RESULTS: Two distinct subgroups were identified by unsupervised machine learning and characterized by differing patterns of clinical features. Patients in Cluster 2 had significantly worse conditions and prognoses than those in Cluster 1. For the novel ASO subtypes, a nomogram was developed using six predictive factors, namely, platelet count, ankle brachial index, Rutherford category, operation method, hypertension, and diabetes status. The nomogram achieved excellent discrimination for predicting membership in the two identified clusters, with an area under the curve of 0.96 and 0.95 in training cohort and internal test cohort. CONCLUSION: This study demonstrated that unsupervised machine learning can reveal novel phenotypic subgroups of patients with varying prognostic risk who underwent endovascular therapy. The prediction model developed could support clinical decision-making and risk counseling for this complex patient population. Further external validation is warranted to assess the generalizability of the findings.
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Arteriosclerosis Obliterante , Procedimientos Endovasculares , Aprendizaje Automático no Supervisado , Humanos , Femenino , Masculino , Procedimientos Endovasculares/métodos , Estudios Retrospectivos , Arteriosclerosis Obliterante/cirugía , Anciano , Persona de Mediana Edad , Nomogramas , Pronóstico , Aprendizaje AutomáticoRESUMEN
End-stage liver diseases, such as cirrhosis and liver cancer caused by hepatitis B, are often combined with hepatic encephalopathy (HE); ammonia poisoning is posited as one of its main pathogenesis mechanisms. Ammonia is closely related to autophagy, but the molecular mechanism of ammonia's regulatory effect on autophagy in HE remains unclear. Sialylation is an essential form of glycosylation. In the nervous system, abnormal sialylation affects various physiological processes, such as neural development and synapse formation. ST3 ß|-galactoside α2,|3-sialyltransferase 6 (ST3GAL6) is one of the significant glycosyltransferases responsible for adding α2,3-linked sialic acid to substrates and generating glycan structures. We found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction, and the expression levels of α2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3 (LC3) and Beclin-1 were upregulated in ammonia-induced astrocytes. These findings suggest that ST3GAL6 is related to autophagy in HE. Therefore, we aimed to determine the regulatory relationship between ST3GAL6 and autophagy. We found that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way of Maackia amurensis lectin-II (MAL-II) and neuraminidase can inhibit autophagy. In addition, silencing the expression of ST3GAL6 can downregulate the expression of heat shock protein ß8 (HSPB8) and Bcl2-associated athanogene 3 (BAG3). Notably, the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 expression. Our results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.
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Proteínas Reguladoras de la Apoptosis , Autofagia , Encéfalo , Encefalopatía Hepática , Polisacáridos , Sialiltransferasas , Sialiltransferasas/metabolismo , Sialiltransferasas/genética , Animales , Ratones , Polisacáridos/metabolismo , Encefalopatía Hepática/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Encéfalo/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Amoníaco/metabolismo , Astrocitos/metabolismo , Masculino , beta-Galactosida alfa-2,3-Sialiltransferasa , Chaperonas Moleculares/metabolismo , Proteínas de Choque Térmico/metabolismo , Humanos , Silenciador del Gen , Proteínas Asociadas a Microtúbulos/metabolismo , Ratones Endogámicos C57BLRESUMEN
Hepatocellular carcinoma (HCC) is a prevalent malignancy characterized by an exceedingly high recurrence rate post-surgery, significantly impairing the prognosis of HCC patients. However, a standard in-care strategy for postoperative therapy is still lacking. Although encouraging results have been obtained in a newly published clinical trial for postoperative therapy by targeting the vascular endothelial growth factor (VEGF) and programmed death ligand 1 (anti-PD-L1), its efficacy remains constrained. Combining a hemostatic hydrogel with a nanoparticle-based drug delivery system presents an opportunity to optimize the antitumor effect. Herein, we developed a nanoplatform, termed HMSN@Sor/aP@Gel, comprising a hemostatic fibrin hydrogel and functionalized hollow mesoporous silica nanoparticles (HMSNs) loaded with sorafenib and anti-PD-L1 for locally administered targeted-immunotherapy to prevent the postoperative recurrence and metastasis of HCC. The antitumor mechanism is grounded in dual inhibition of Ras/Raf/MEK/ERK (MAPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathways, synergistically complemented by PD-L1 blockade. HMSN@Sor/aP@Gel facilitates dendritic cell maturation, enhances cytotoxic T-lymphocyte infiltration, promotes the polarization of tumor-associated macrophages to M1 phenotype, induces tumor immunogenic cell death, reverses immunosuppression, and establishes immune memory to counter postoperative recurrence. Animal studies corroborate that HMSN@Sor/aP@Gel-mediated targeted immunotherapy significantly impedes primary and metastatic tumor growth and establishes immune memory to prevent recurrence post-surgery. This investigation presents a promising strategy for postoperative therapy with considerable potential for clinical translation.
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Carcinoma Hepatocelular , Hidrogeles , Inmunoterapia , Neoplasias Hepáticas , Nanopartículas , Recurrencia Local de Neoplasia , Sorafenib , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/inmunología , Hidrogeles/química , Hidrogeles/administración & dosificación , Animales , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/inmunología , Nanopartículas/administración & dosificación , Nanopartículas/química , Humanos , Recurrencia Local de Neoplasia/prevención & control , Inmunoterapia/métodos , Sorafenib/administración & dosificación , Sorafenib/uso terapéutico , Sorafenib/farmacología , Ratones , Hemostáticos/administración & dosificación , Hemostáticos/química , Hemostáticos/uso terapéutico , Dióxido de Silicio/química , Dióxido de Silicio/administración & dosificación , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Masculino , Ratones Endogámicos BALB C , Fibrina/administración & dosificaciónRESUMEN
ABSTRACT: Sleep disturbances are among the most prevalent neuropsychiatric symptoms in individuals who have recovered from severe acute respiratory syndrome coronavirus 2 infections. Previous studies have demonstrated abnormal brain structures in patients with sleep disturbances who have recovered from coronavirus disease 2019 (COVID-19). However, neuroimaging studies on sleep disturbances caused by COVID-19 are scarce, and existing studies have primarily focused on the long-term effects of the virus, with minimal acute phase data. As a result, little is known about the pathophysiology of sleep disturbances in the acute phase of COVID-19. To address this issue, we designed a longitudinal study to investigate whether alterations in brain structure occur during the acute phase of infection, and verified the results using 3-month follow-up data. A total of 26 COVID-19 patients with sleep disturbances (aged 51.5 ± 13.57 years, 8 women and 18 men), 27 COVID-19 patients without sleep disturbances (aged 47.33 ± 15.98 years, 9 women and 18 men), and 31 age-and gender-matched healthy controls (aged 49.19 ± 17.51 years, 9 women and 22 men) were included in this study. Eleven COVID-19 patients with sleep disturbances were included in a longitudinal analysis. We found that COVID-19 patients with sleep disturbances exhibited brain structural changes in almost all brain lobes. The cortical thicknesses of the left pars opercularis and left precuneus were significantly negatively correlated with Pittsburgh Sleep Quality Index scores. Additionally, we observed changes in the volume of the hippocampus and its subfield regions in COVID-19 patients compared with the healthy controls. The 3-month follow-up data revealed indices of altered cerebral structure (cortical thickness, cortical grey matter volume, and cortical surface area) in the frontal-parietal cortex compared with the baseline in COVID-19 patients with sleep disturbances.Our findings indicate that the sleep disturbances patients had altered morphology in the cortical and hippocampal structures during the acute phase of infection and persistent changes in cortical regions at 3 months post-infection. These data improve our understanding of the pathophysiology of sleep disturbances caused by COVID-19.
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Nonalcoholic fatty liver disease (NAFLD) has emerged as the predominant chronic liver condition globally, and underdiagnosis is common, particularly in mild cases, attributed to the asymptomatic nature and traditional ultrasonography's limited sensitivity to detect early-stage steatosis. Consequently, patients may experience progressive liver pathology. The objective of this research is to ascertain the efficacy of serum glycan glycopatterns as a potential diagnostic biomarker, with a particular focus on the disease's early stages. We collected a total of 170 serum samples from volunteers with mild-NAFLD (Mild), severe-NAFLD (Severe), and non-NAFLD (None). Examination via lectin microarrays has uncovered pronounced disparities in serum glycopatterns identified by 19 distinct lectins. Following this, we employed four distinct machine learning algorithms to categorize the None, Mild, and Severe groups, drawing on the alterations observed in serum glycopatterns. The gradient boosting decision tree (GBDT) algorithm outperformed other models in diagnostic accuracy within the validation set, achieving an accuracy rate of 95% in differentiating the None group from the Mild group. Our research indicates that employing lectin microarrays to identify alterations in serum glycopatterns, when integrated with advanced machine learning algorithms, could constitute a promising approach for the diagnosis of NAFLD, with a special emphasis on its early detection.
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Biomarcadores , Lectinas , Aprendizaje Automático , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Biomarcadores/sangre , Lectinas/sangre , Femenino , Masculino , Adulto , Persona de Mediana Edad , Algoritmos , Polisacáridos/sangre , Polisacáridos/química , Glicoproteínas/sangreRESUMEN
An Al-Si matrix foam sandwich (AFS) with 6063 Al alloy cover sheets was fabricated by hot rolling combined with melt foaming. A foamable AlSiMg1/SiCp matrix precursor was prepared by the melting route. Hot rolling at 480 °C was carried out to obtain a mechanical bonding interface between the cover sheet and the foamable precursor. Meanwhile, the pore structure of the AFS was deeply affected by the foaming temperature and foaming time during the foaming process. Different pore growth mechanics of the crack-like pore disappearance mechanism (CDM) and pore active expansion mechanism (AEM) were concluded based on the pressure difference in pores inside and outside. Three bending tests were applied to three types of AFSs with different pore structures to evaluate the relation between pore structures and AFS mechanical properties. The bending property of the AFS with fewer layers of pores is like that of a dense material. The bending property of the AFS with a pore size in the range of 0~1 mm presents a typical sandwich shear failure mode. The AFS with a uniform pore structure, in which the shapes of the pores are predominately polygons and the pore diameter is concentrated in the range of 0.5~3 mm, processes a good energy absorption capacity, and the bending stress-strain curve fluctuates greatly after the first stress drop.
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BACKGROUND: The pathophysiology of coronasomnia remains unclear. This study aimed to investigate changes in white matter (WM) microstructure and inflammatory factors in patients with sleep disorders (SD) characterized by poor sleep quantity, quality, or timing following coronavirus disease 2019 (COVID-19) infection in the acute phase (within one month) and whether these changes could be recovered at 3-month follow-up. METHODS: 29 acute COVID-19 patients with SD (COVID_SD) and 27 acute COVID-19 patients without SD (COVID_NonSD) underwent diffusion tensor imaging (DTI), tested peripheral blood inflammatory cytokines level, and measured Pittsburgh Sleep Quality Index (PSQI), and matched 30 uninfected healthy controls. Analyzed WM abnormalities between groups in acute phase and explored its changes in COVID_SD at 3-month follow-up by using tract-based spatial statistics (TBSS). Correlations between DTI and clinical data were examined using Spearman partial correlation analysis. RESULTS: Both COVID_SD and COVID_NonSD exhibited widespread WM microstructure abnormalities. The COVID_SD group showed specific WM microstructure changes in right inferior fronto-occipital fasciculus (IFOF) (lower fractional anisotropy [FA]/axial diffusivity [AD] and higher radial diffusivity [RD]) and left corticospinal tract (CST) (higher FA and lower RD) and higher interleukin-1ß (IL-1ß) compared with COVID_NonSD group. These WM abnormalities and IL-1ß levels were correlated PSQI score. After 3 months, the IFOF integrity and IL-1ß levels tended to return to normal accompanied by symptom improvement in the COVID_SD relative to baseline. CONCLUSION: Abnormalities in right IFOF and left CST and elevated IL-1ß levels were important neurophenotypes correlated with COVID_SD, which might provide new insights into the pathogenesis of neuroinflammation in SD patients induced by COVID-19.
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COVID-19 , Trastornos del Inicio y del Mantenimiento del Sueño , Sustancia Blanca , Humanos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Imagen de Difusión Tensora/métodos , Fibras Nerviosas , Encéfalo/diagnóstico por imagen , Encéfalo/patologíaRESUMEN
We aim to investigate the alterations in gray matter for subjective cognitive decline (SCD) and mild cognitive impairment (MCI) from the perspective of the human connectome. High-resolution T1-weighted images were acquired from 54 patients with SCD, 95 patients with MCI, and 65 healthy controls (HC). Morphological brain networks (MBN) were constructed using similarities in the distribution of gray matter volumes between regions. The strength of morphological connections and topographic metrics derived from the graph-theoretical analysis were compared. Furthermore, we assessed the relationship between the observed morphological abnormalities and disease severity. According to the results, we found a significantly decreased morphological connection between the somatomotor network and ventral attention network in SCD compared to HC and MCI compared to SCD. The graph-theoretic analysis illustrated disruptions in the whole network organization, where the normalized shortest path increased and the global efficiency (Eg) decreased in MCI compared to SCD. In addition, Montreal Cognitive Assessment scores of SCD patients had a significantly negative correlation with Eg. The primary limitations of the present study include the cross-sectional design, no enrolled AD patients, no assessment of amyloidosis, and the need for more comprehensive neuropsychological tests. Our findings indicate the abnormalities of morphological networks at early stages in the AD continuum, which could be interpreted as compensatory changes to retain a normal level of cognitive function. The present study could provide new insight into the mechanism of AD.
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Encéfalo , Disfunción Cognitiva , Conectoma , Imagen por Resonancia Magnética , Red Nerviosa , Humanos , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/fisiopatología , Femenino , Masculino , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Anciano , Imagen por Resonancia Magnética/métodos , Conectoma/métodos , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/patología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estudios Transversales , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/patología , Vías Nerviosas/fisiopatologíaRESUMEN
Introduction: This study aimed to evaluate morphological changes in cortical and subcortical regions and their asymmetrical differences in individuals with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). These morphological changes may provide valuable insights into the early diagnosis and treatment of Alzheimer's disease (AD). Methods: We conducted structural MRI scans on a cohort comprising 62 SCD patients, 97 MCI patients, and 70 age-, sex-, and years of education-matched healthy controls (HC). Using Freesurfer, we quantified surface area, thickness, the local gyrification index (LGI) of cortical regions, and the volume of subcortical nuclei. Asymmetry measures were also calculated. Additionally, we explored the correlation between morphological changes and clinical variables related to cognitive decline. Results: Compared to HC, patients with MCI exhibited predominantly left-sided surface morphological changes in various brain regions, including the transverse temporal gyrus, superior temporal gyrus, insula, and pars opercularis. SCD patients showed relatively minor surface morphological changes, primarily in the insula and pars triangularis. Furthermore, MCI patients demonstrated reduced volumes in the anterior-superior region of the right hypothalamus, the fimbria of the bilateral hippocampus, and the anterior region of the left thalamus. These observed morphological changes were significantly associated with clinical ratings of cognitive decline. Conclusion: The findings of this study suggest that cortical and subcortical morphometric changes may contribute to cognitive impairment in MCI, while compensatory mechanisms may be at play in SCD to preserve cognitive function. These insights have the potential to aid in the early diagnosis and treatment of AD.
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Neural interfaces for stable access to the spinal cord (SC) electrical activity can benefit patients with motor dysfunctions. Invasive high-density electrodes can directly extract signals from SC neuronal populations that can be used for the facilitation, adjustment, and reconstruction of motor actions. However, developing neural interfaces that can achieve high channel counts and long-term intraspinal recording remains technically challenging. Here, a biocompatible SC hyperflexible electrode array (SHEA) with an ultrathin structure that minimizes mechanical mismatch between the interface and SC tissue and enables stable single-unit recording for more than 2 months in mice is demonstrated. These results show that SHEA maintains stable impedance, signal-to-noise ratio, single-unit yield, and spike amplitude after implantation into mouse SC. Gait analysis and histology show that SHEA implantation induces negligible behavioral effects and Inflammation. Additionally, multi-unit signals recorded from the SC ventral horn can predict the mouse's movement trajectory with a high decoding coefficient of up to 0.95. Moreover, during step cycles, it is found that the neural trajectory of spikes and low-frequency local field potential (LFP) signal exhibits periodic geometry patterns. Thus, SHEA can offer an efficient and reliable SC neural interface for monitoring and potentially modulating SC neuronal activity associated with motor dysfunctions.
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Movimiento , Neuronas , Humanos , Ratones , Animales , Electrodos , Neuronas/fisiología , Movimiento/fisiología , Electroencefalografía/métodosRESUMEN
Pseudorabies (PR) is an acute and severe infectious disease caused by pseudorabies virus (PRV). Once the virus infects pigs, it is difficult to eliminate, resulting in major economic losses to the global pig industry. In addition, reports of human infection with PRV suggest that the virus is a potential threat to human health; thus, its significance to public health should be considered. In this paper, the anti-PRV activities of emodin in vitro and in vivo, and its mechanism of action were studied. The results showed that emodin inhibited the proliferation of PRV in PK15 cells in a dose-dependent manner, with an IC50 of 0.127 mg/mL and a selection index of 5.52. The addition of emodin at different stages of viral infection showed that emodin inhibited intracellular replication. Emodin significantly inhibited the expression of the IE180, EP0, UL29, UL44, US6, and UL27 genes of PRV within 48 h. Emodin also significantly inhibited the expression of PRV gB and gD proteins. The molecular docking results suggested that emodin might form hydrogen bonds with PRV gB and gD proteins and affect the structure of viral proteins. Emodin effectively inhibited the apoptosis induced by PRV infection. Moreover, emodin showed a good protective effect on PRV-infected mice. During the experimental period, all the control PRV-infected mice died resulting in a survival rate of 0%, while the survival rate of emodin-treated mice was 28.5%. Emodin also significantly inhibited the replication of PRV in the heart, liver, brain, kidneys and lungs of mice and alleviated tissue and organ damage caused by PRV infection. Emodin was able to combat viral infection by regulating the levels of the cytokines TNF-α, IFN-γ, IL-6, and IL-4 in the sera of infected mice. These results indicate that emodin has good anti-PRV activity in vitro and in vivo, and is expected to be a new agent for the prevention and control of PRV infection.