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1.
Nature ; 627(8002): 67-72, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38448698

RESUMEN

Ordinary metals contain electron liquids within well-defined 'Fermi' surfaces at which the electrons behave as if they were non-interacting. In the absence of transitions to entirely new phases such as insulators or superconductors, interactions between electrons induce scattering that is quadratic in the deviation of the binding energy from the Fermi level. A long-standing puzzle is that certain materials do not fit this 'Fermi liquid' description. A common feature is strong interactions between electrons relative to their kinetic energies. One route to this regime is special lattices to reduce the electron kinetic energies. Twisted bilayer graphene1-4 is an example, and trihexagonal tiling lattices (triangular 'kagome'), with all corner sites removed on a 2 × 2 superlattice, can also host narrow electron bands5 for which interaction effects would be enhanced. Here we describe spectroscopy revealing non-Fermi-liquid behaviour for the ferromagnetic kagome metal Fe3Sn2 (ref. 6). We discover three C3-symmetric electron pockets at the Brillouin zone centre, two of which are expected from density functional theory. The third and most sharply defined band emerges at low temperatures and binding energies by means of fractionalization of one of the other two, most likely on the account of enhanced electron-electron interactions owing to a flat band predicted to lie just above the Fermi level. Our discovery opens the topic of how such many-body physics involving flat bands7,8 could differ depending on whether they arise from lattice geometry or from strongly localized atomic orbitals9,10.

2.
Brief Bioinform ; 24(3)2023 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-37139553

RESUMEN

Deciphering cell-type-specific 3D structures of chromatin is challenging. Here, we present InferLoop, a novel method for inferring the strength of chromatin interaction using single-cell chromatin accessibility data. The workflow of InferLoop is, first, to conduct signal enhancement by grouping nearby cells into bins, and then, for each bin, leverage accessibility signals for loop signals using a newly constructed metric that is similar to the perturbation of the Pearson correlation coefficient. In this study, we have described three application scenarios of InferLoop, including the inference of cell-type-specific loop signals, the prediction of gene expression levels and the interpretation of intergenic loci. The effectiveness and superiority of InferLoop over other methods in those three scenarios are rigorously validated by using the single-cell 3D genome structure data of human brain cortex and human blood, the single-cell multi-omics data of human blood and mouse brain cortex, and the intergenic loci in the GWAS Catalog database as well as the GTEx database, respectively. In addition, InferLoop can be applied to predict loop signals of individual spots using the spatial chromatin accessibility data of mouse embryo. InferLoop is available at https://github.com/jumphone/inferloop.


Asunto(s)
Cromatina , Genoma , Humanos , Animales , Ratones , Cromatina/genética , Multiómica
3.
Brain ; 147(9): 3048-3058, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-38426222

RESUMEN

Frontotemporal dementia (FTD) is a disease of high heterogeneity, apathy and disinhibition present in all subtypes of FTD and imposes a significant burden on families/society. Traditional neuroimaging analysis has limitations in elucidating the network localization due to individual clinical and neuroanatomical variability. The study aims to identify the atrophy network map associated with different FTD clinical subtypes and determine the specific localization of the network for apathy and disinhibition. Eighty FTD patients [45 behavioural variant FTD (bvFTD) and 35 semantic variant progressive primary aphasia (svPPA)] and 58 healthy controls at Xuanwu Hospital were enrolled as Dataset 1; 112 FTD patients including 50 bvFTD, 32 svPPA and 30 non-fluent variant PPA (nfvPPA) cases, and 110 healthy controls from the Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) dataset were included as Dataset 2. Initially, single-subject atrophy maps were defined by comparing cortical thickness in each FTD patient versus healthy controls. Next, the network of brain regions functionally connected to each FTD patient's location of atrophy was determined using seed-based functional connectivity in a large (n = 1000) normative connectome. Finally, we used atrophy network mapping to define clinical subtype-specific network (45 bvFTD, 35 svPPA and 58 healthy controls in Dataset 1; 50 bvFTD, 32 svPPA, 30 nfvPPA and 110 healthy controls in Dataset 2) and symptom-specific networks [combined Datasets 1 and 2, apathy without depression versus non-apathy without depression (80:26), disinhibition versus non-disinhibition (88:68)]. We compare the result with matched symptom networks derived from patients with focal brain lesions or conjunction analysis. Through the analysis of two datasets, we identified heterogeneity in atrophy patterns among FTD patients. However, these atrophy patterns are connected to a common brain network. The primary regions affected by atrophy in FTD included the frontal and temporal lobes, particularly the anterior temporal lobe. bvFTD connects to frontal and temporal cortical areas, svPPA mainly impacts the anterior temporal region and nfvPPA targets the inferior frontal gyrus and precentral cortex regions. The apathy-specific network was localized in the orbital frontal cortex and ventral striatum, while the disinhibition-specific network was localized in the bilateral orbital frontal gyrus and right temporal lobe. Apathy and disinhibition atrophy networks resemble known motivational and criminal lesion networks, respectively. A significant correlation was found between the apathy/disinhibition scores and functional connectivity between atrophy maps and the peak of the networks. This study localizes the common network of clinical subtypes and main symptoms in FTD, guiding future FTD neuromodulation interventions.


Asunto(s)
Atrofia , Demencia Frontotemporal , Imagen por Resonancia Magnética , Humanos , Demencia Frontotemporal/patología , Demencia Frontotemporal/diagnóstico por imagen , Demencia Frontotemporal/fisiopatología , Demencia Frontotemporal/psicología , Atrofia/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Imagen por Resonancia Magnética/métodos , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/patología , Red Nerviosa/fisiopatología , Apatía/fisiología , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Conectoma
4.
Mol Pain ; 20: 17448069241232349, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38288478

RESUMEN

Background. Neuro-inflammatory response promotes the initiation and sustenance of lumbar disc herniation (LDH). Protectin D1 (PD1), as a new type of specialized pro-resolving mediator (SPM), can improve the prognosis of various inflammatory diseases. Recent studies have shown that over representation of calcitonin gene-related peptides (CGRP) may activate nociceptive signaling following nerve injury. Silent information regulator 1 (SIRT1) is ubiquitously expressed in the dorsal horn of the spinal cord and plays a role in the pathogenesis of LDH. In this study, we investigated the analgesic effects of PD1 and elucidated the impact of neurogenic inflammation in the pathogenesis of neuropathic pain induced by non-compressive lumbar disc herniation (NCLDH) in a rat model. Methods. NCLDH models were established by applying protruding autologous nucleus pulposus to the L5 Dorsal root ganglion (DRG). PD1, SIRT1 antagonist or agonist, CGRP or antagonist were administered as daily intrathecal injections for three consecutive days postoperatively. Behavioral tests were conducted to assess mechanical and thermal hyperalgesia. The ipsilateral lumbar (L4-6) segment of the spinal dorsal horn was isolated for further analysis. Alterations in the release of SIRT1 and CGRP were explored using western blot and immunofluorescence. Results. Application of protruded nucleus (NP) materials to the DRG induced mechanical and thermal allodynia symptoms, and deregulated the expression of pro-inflammatory and anti-inflammatory cytokines in rats. Intrathecal delivery of PD1 significantly reversed the NCLDH-induced imbalance in neuro-inflammatory response and alleviated the symptoms of mechanical and thermal hyperalgesia. In addition, NP application to the DGRs resulted the spinal upregulation of CGRP and SIRT1 expression, which was almost restored by intrathecal injection of PD1 in a dose-dependent manner. SIRT1 antagonist or agonist and CGRP or antagonist treatment further confirmed the result. Conclusion. Our findings indicate PD1 has a potent analgesic effect, and can modulate neuro-inflammation by regulating SIRT1-mediated CGRP signaling in NCLDH.


Asunto(s)
Ácidos Docosahexaenoicos , Desplazamiento del Disco Intervertebral , Ratas , Animales , Desplazamiento del Disco Intervertebral/tratamiento farmacológico , Desplazamiento del Disco Intervertebral/complicaciones , Hiperalgesia/metabolismo , Péptido Relacionado con Gen de Calcitonina/metabolismo , Ratas Sprague-Dawley , Sirtuina 1/metabolismo , Calcitonina/metabolismo , Asta Dorsal de la Médula Espinal/metabolismo , Analgésicos/farmacología , Ganglios Espinales/metabolismo , Modelos Animales de Enfermedad
5.
Br J Haematol ; 204(3): 1082-1085, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37932927

RESUMEN

Currently, there is no effective treatment for refractory/relapsed (R/R) autoimmune haemolytic anaemia (AIHA), associated with poor quality of life. Bruton tyrosine kinase inhibitors have begun to be used in some autoimmune diseases. We initiated the clinical trial of orelabrutinib treatment on R/R AIHA/Evans Syndrome, which is in progress. The preliminary results showed that nine of the 12 enrolled patients responded to orelabrutinib treatment. Here, we reported three cases who have completed the treatment and were followed up for 6 months, achieving complete or partial remission. Orelabrutinib is expected to become a new second-line treatment for R/R AIHA/Evans syndrome.


Asunto(s)
Anemia Hemolítica Autoinmune , Piperidinas , Piridinas , Trombocitopenia , Humanos , Anemia Hemolítica Autoinmune/terapia , Proyectos Piloto , Calidad de Vida
6.
Brief Bioinform ; 23(5)2022 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-35870444

RESUMEN

The quantification of developmental potential is critical for determining developmental stages and identifying essential molecular signatures in single-cell studies. Here, we present FitDevo, a novel method for inferring developmental potential using scRNA-seq data. The main idea of FitDevo is first to generate sample-specific gene weight (SSGW) and then infer developmental potential by calculating the correlation between SSGW and gene expression. SSGW is generated using a generalized linear model that combines sample-specific information and gene weight learned from a training dataset covering scRNA-seq data of 17 previously published datasets. We have rigorously validated FitDevo's effectiveness using a testing dataset with scRNA-seq data from 28 existing datasets and have also demonstrated its superiority over current methods. Furthermore, FitDevo's broad application scope has been illustrated using three practical scenarios: deconvolution analysis of epidermis, spatial transcriptomic data analysis of hearts and intestines, and developmental potential analysis of breast cancer. The source code and related data are available at https://github.com/jumphone/fitdevo.


Asunto(s)
Perfilación de la Expresión Génica , Análisis de la Célula Individual , Perfilación de la Expresión Génica/métodos , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos , Programas Informáticos , Transcriptoma
7.
Ann Hematol ; 103(9): 3627-3637, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38647678

RESUMEN

Iron contributes to tumor initiation and progression; however, excessive intracellular free Fe2+ can be toxic to cancer cells. Our findings confirmed that multiple myeloma (MM) cells exhibited elevated intracellular iron levels and increased ferritin, a key protein for iron storage, compared with normal cells. Interestingly, Bortezomib (BTZ) was found to trigger ferritin degradation, increase free intracellular Fe2+, and promote ferroptosis in MM cells. Subsequent mechanistic investigation revealed that BTZ effectively increased NCOA4 levels by preventing proteasomal degradation in MM cells. When we knocked down NCOA4 or blocked autophagy using chloroquine, BTZ-induced ferritin degradation and the increase in intracellular free Fe2+ were significantly reduced in MM cells, confirming the role of BTZ in enhancing ferritinophagy. Furthermore, the combination of BTZ with RSL-3, a specific inhibitor of GPX4 and inducer of ferroptosis, synergistically promoted ferroptosis in MM cell lines and increased cell death in both MM cell lines and primary MM cells. The induction of ferroptosis inhibitor liproxstatin-1 successfully counteracted the synergistic effect of BTZ and RSL-3 in MM cells. Altogether, our findings reveal that BTZ elevates intracellular free Fe2+ by enhancing NCOA4-mediated ferritinophagy and synergizes with RSL-3 by increasing ferroptosisin MM cells.


Asunto(s)
Bortezomib , Sinergismo Farmacológico , Ferritinas , Ferroptosis , Hierro , Mieloma Múltiple , Coactivadores de Receptor Nuclear , Humanos , Mieloma Múltiple/metabolismo , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Coactivadores de Receptor Nuclear/metabolismo , Coactivadores de Receptor Nuclear/genética , Bortezomib/farmacología , Ferritinas/metabolismo , Ferroptosis/efectos de los fármacos , Hierro/metabolismo , Línea Celular Tumoral , Autofagia/efectos de los fármacos , Antineoplásicos/farmacología , Carbolinas
8.
Environ Sci Technol ; 58(35): 15381-15394, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39136294

RESUMEN

China is confronting the dual challenges of air pollution and climate change, mandating the co-control of air pollutants and CO2 emissions from their shared sources. Here we identify key sources for co-control that prioritize the mitigation of PM2.5-related health burdens, given the homogeneous impacts of CO2 emissions from various sources. By applying an integrated analysis framework that consists of a detailed emission inventory, a chemical transport model, a multisource fused dataset, and epidemiological concentration-response functions, we systematically evaluate the contribution of emissions from 390 sources (30 provinces and 13 socioeconomic sectors) to PM2.5-related health impacts and CO2 emissions, as well as the marginal health benefits of CO2 abatement across China. The estimated source-specific contributions exhibit substantial disparities, with the marginal benefits varying by 3 orders of magnitude. The rural residential, transportation, metal, and power and heating sectors emerge as pivotal sources for co-control, with regard to their relatively large marginal benefits or the sectoral total benefits. In addition, populous and heavily industrialized provinces such as Shandong and Henan are identified as the key regions for co-control. Our study highlights the significance of incorporating health benefits into formulating air pollution and carbon co-control strategies for improving the overall social welfare.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Dióxido de Carbono , China , Dióxido de Carbono/análisis , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Cambio Climático , Monitoreo del Ambiente
9.
BMC Cardiovasc Disord ; 24(1): 72, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38267838

RESUMEN

BACKGROUND: Cancer and coronary artery disease (CAD) is reported to often co-exist in same individuals, however, whether cancer is directly associated with anatomical severity of CAD is rarely studied. The present study aimed to observe the relationship between newly diagnosed cancer and anatomical severity of CAD, moreover, to investigate effect of inflammation on the relationship of cancer with CAD. METHODS: 374 patients with newly diagnosed cancer who underwent coronary angiography (CAG) were enrolled. Through 1:3 propensity score matching (PSM) to cancer patients based on the age and gender among 51,106 non-cancer patients who underwent CAG, 1122 non-cancer patients were selected as control patients. Anatomical severity of CAD was assessed using SYNTAX score (SXscore) based on coronary angiographic image. SXscore ≤ 22 (highest quartile) was defined as SX-low, and SXscore > 22 as SX-high. The ratio of neutrophil to lymphocyte count (NLR) was used to describe inflammation level. Association between cancer and the anatomical severity of CAD was investigated using logistic regression. RESULTS: Univariate logistic regression analysis showed a correlation between cancer and anatomical severity of CAD (OR: 1.419, 95% CI: 1.083-1.859; P = 0.011). Cancer was associated with increased risk of SX-high after adjusted for common risk factors of CAD (OR: 1.598, 95% CI: 1.172-2.179, P = 0.003). Significant association between cancer and SX-high was revealed among patients with high inflammation (OR: 1.656, 95% CI: 1.099-2.497, P = 0.016), but not among patients with low inflammation (OR: 1.530, 95% CI: 0.973-2.498, P = 0.089). CONCLUSIONS: Cancer was associated with severity of CAD, however, the association between the two diseases was significant among patients with high inflammation rather than among patients with low inflammation.


Asunto(s)
Enfermedad de la Arteria Coronaria , Neoplasias , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Neoplasias/diagnóstico , Neoplasias/epidemiología , Angiografía Coronaria , Inflamación , Factores de Riesgo
10.
Neurol Sci ; 45(2): 557-564, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37668827

RESUMEN

BACKGROUND: The mild behavioral impairment checklist (MBI-C) designed to capture neuropsychiatric symptoms in the whole spectrum of elder with or without dementia, have been verified in mild behavioral impairment, mild cognitive impairment and Alzheimer's Disease, but never used in the behavioral variant of frontotemporal dementia (bvFTD). METHODS: Fifty-two patients with bvFTD (mild, n = 30; moderate-severe, n = 22) and 82 community-dwelling elderly individuals (HCs) were enrolled. All subjects were assessed with a full neuropsychological scale including the MBI-C, Neuropsychiatric Inventory Questionnaire (NPI-Q), and Frontal Behavioral Inventory (FBI). Receiver operating characteristic curves were drawn to analyze the sensitivity and specificity of the MBI-C, NPI-Q, and FBI, and cutoff points were determined using the Youden index. RESULTS: The MBI-C and domain scores in all patients with bvFTD were significantly higher than those in HCs. The most common symptoms of bvFTD were apathy (82.7%) and impulse dyscontrol (80.8%). The MBI-C score was positively correlated with the NPI-Q, FBI, and Activities of Daily Living. For differentiating patients with both bvFTD and mild bvFTD from HCs, the optimal MBI-C cutoff point was 5.5 with a sensitivity of 100% and specificity of 82%, and its sensitivity was higher than that of the NPI-Q and FBI. CONCLUSION: The MBI-C is a sensitive tool for screening behavioral and psychological symptoms in patients with bvFTD, even in the early stages of the disease.


Asunto(s)
Disfunción Cognitiva , Demencia Frontotemporal , Humanos , Anciano , Demencia Frontotemporal/diagnóstico , Lista de Verificación , Actividades Cotidianas , Pruebas Neuropsicológicas , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , China
11.
Neurol Sci ; 45(8): 3573-3582, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38772979

RESUMEN

INTRODUCTION: Identifying coronavirus disease 2019 (COVID-19)-related encephalitis without clear etiological evidence is clinically challenging. The distinctions between this condition and other prevalent encephalitis types remain unknown. Therefore, we aimed to explore the similarities and differences in the clinical characteristics of COVID-19-related encephalitis and other encephalitis types. METHODS: Adult patients with encephalitis admitted to the neurology department at Xuanwu Hospital were enrolled and categorized into the following six groups based on the results of metagenomic next-generation sequencing and autoimmune antibody detection in cerebrospinal fluid (CSF): COVID-19-related encephalitis (n = 36), herpes simplex virus type 1 encephalitis (HSV-1 encephalitis; n = 28), human herpesvirus 3 encephalitis (HHV-3 encephalitis; n = 10), NMDAR-antibody encephalitis (n = 18), LGI1-antibody encephalitis (n = 12), and GABAB-antibody encephalitis (n = 8). RESULTS: The predominant characteristics of COVID-19-related encephalitis include a low incidence of seizures (38.9%), cognitive defects (30.6%), and meningeal irritation signs (8.3%). Compared with HSV-1 and HHV-3 encephalitis, COVID-19-related encephalitis exhibited lower white blood cell count (2.5 count/mm3), protein (32.2 mg/dL), and immunoglobulin M, G, and A levels (0.09, 3.2, and 0.46 mg/dL, respectively) in the CSF tests. Abnormal imaging findings were present in only 36.1% of COVID-19-related encephalitis cases, mostly showing diffuse inflammation scattered in various parts, which differed from HSV-1 encephalitis. Additionally, COVID-19-related encephalitis exhibited significant differences in clinical symptoms and CSF white blood cell counts compared with NMDAR-antibody encephalitis; however, it showed limited differences compared with LGI1-antibody and GABAB-antibody encephalitis. DISCUSSION: COVID-19-related encephalitis and herpes virus or autoimmune encephalitis differ clinically. Symptoms and auxiliary examinations can be used as distinguishing tools.


Asunto(s)
COVID-19 , Encefalitis por Herpes Simple , Encefalitis , Enfermedad de Hashimoto , Humanos , COVID-19/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Adulto , Encefalitis/diagnóstico , Encefalitis/líquido cefalorraquídeo , Encefalitis por Herpes Simple/líquido cefalorraquídeo , Encefalitis por Herpes Simple/diagnóstico , Encefalitis por Herpes Simple/complicaciones , Enfermedad de Hashimoto/líquido cefalorraquídeo , Enfermedad de Hashimoto/diagnóstico , Anciano , Autoanticuerpos/líquido cefalorraquídeo , Autoanticuerpos/sangre , Encefalitis Viral/diagnóstico , Encefalitis Viral/líquido cefalorraquídeo , SARS-CoV-2 , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/líquido cefalorraquídeo
12.
J Adv Nurs ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164078

RESUMEN

AIMS: To analyse the current status of psychological resilience in Parkinson's disease (PD) patients and its correlation with social support and coping style. DESIGN: A cross-sectional study. METHODS: PD patients hospitalized in a tertiary-level hospital in Shijiazhuang, Hebei Province, from March 2022 to March 2023 were selected for the study using the convenience sampling method. A general information questionnaire, psychological resilience scale, Medical Coping Modes Questionnaire and Perceived Social Support Scale were used to investigate 111 cases of PD. SPSS 25.0 software was used for statistical analysis. The data were analysed using independent samples t-test, one-way ANOVA, multiple linear regression analysis and the Pearson correlation coefficient. RESULTS: Parkinson's disease patients have a moderate level of psychological resilience. The results of the Pearson correlation analyses showed that the level of psychological resilience was positively correlated with social support and confrontation and was negatively correlated with avoidance and acceptance-resignation. The results of multiple linear regression analysis showed that social support and acceptance-resignation were the influencing factors of psychological resilience in PD patients. CONCLUSION: The psychological resilience of PD patients is at a moderate level. Social support and acceptance-resignation are the factors influencing the psychological resilience of PD patients. IMPACT STATEMENT: This study analysed the level of psychological resilience in PD patients and its correlation with social support and coping style from the perspective of positive psychology to provide some reference for targeted clinical interventions. Our study found that social support and acceptance-resignation are influential factors in psychological resilience in PD patients. Medical staff should encourage patients to face the disease positively and their social support should be increased in order to improve their level of psychological resilience. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

13.
Int J Mol Sci ; 25(16)2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39201364

RESUMEN

Monkeypox virus (MPXV) is a cross-kingdom pathogen infecting both humans and wildlife, which poses a significant health risk to the public. Although MPXV attracts broad attention, there is a lack of adequate studies to elucidate pathogenic mechanisms associated with viral infections. In this study, a high-throughput RNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was used to explore the transcriptional and metabolic responses of MPXV A23 protein to HEK293T cells. The protein-protein interactions and signaling pathways were conducted by GO and KEGG analyses. The localization of A23 protein in HEK293T cells was detected by immunofluorescence. A total of 648 differentially expressed genes (DEGs) were identified in cells by RNA-Seq, including 314 upregulated genes and 334 downregulated genes. Additionally, liquid chromatography-tandem mass spectrometry (LC-MS/MS) detected 115 cellular proteins that interact with the A23 proteins. Transcriptomic sequencing analysis revealed that transfection of MPXV A23 protein modulated genes primarily associated with cellular apoptosis and DNA damage repair. Proteomic analysis indicated that this protein primarily interacted with host ribosomal proteins and histones. Following the identification of the nuclear localization sequence RKKR within the A23 protein, a truncated mutant A23ΔRKKR was constructed to investigate the subcellular localization of A23 protein. The wild-type A23 protein exhibits a significantly higher nuclear-to-cytoplasmic ratio, exceeding 1.5, in contrast to the mutant A23ΔRKKR, which has a ratio of approximately 1. Immunofluorescence assays showed that the A23 protein was mainly localized in the nucleus. The integration of transcriptomics and proteomics analysis provides a comprehensive understanding of the interaction between MPXV A23 protein and the host. Our findings highlight the potential role of this enzyme in suppressing host antiviral immune responses and modulating host gene expression.


Asunto(s)
Monkeypox virus , Proteómica , Transcriptoma , Proteínas Virales , Humanos , Células HEK293 , Proteómica/métodos , Proteínas Virales/metabolismo , Proteínas Virales/genética , Monkeypox virus/genética , Monkeypox virus/metabolismo , Espectrometría de Masas en Tándem , Perfilación de la Expresión Génica , Cromatografía Liquida , Proteoma/metabolismo
14.
EMBO J ; 38(15): e101964, 2019 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-31267557

RESUMEN

The IGF1R signaling is important in the malignant progression of cancer. However, overexpression of IGF1R has not been properly assessed in HCC. Here, we revealed that GSTZ1-1, the enzyme in phenylalanine/tyrosine catabolism, is downregulated in HCC, and its expression was negatively correlated with IGF1R. Mechanistically, GSTZ1-1 deficiency led to succinylacetone accumulation, alkylation modification of KEAP1, and NRF2 activation, thus promoting IGF1R transcription by recruiting SP1 to its promoter. Moreover, inhibition of IGF1R or NRF2 significantly inhibited tumor-promoting effects of GSTZ1 knockout in vivo. These findings establish succinylacetone as an oncometabolite, and GSTZ1-1 as an important tumor suppressor by inhibiting NRF2/IGF1R axis in HCC. Targeting NRF2 or IGF1R may be a promising treatment approach for this subset HCC.


Asunto(s)
Carcinoma Hepatocelular/patología , Dietilnitrosamina/efectos adversos , Regulación hacia Abajo , Glutatión Transferasa/genética , Heptanoatos/metabolismo , Neoplasias Hepáticas/patología , Animales , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Células Hep G2 , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Neoplasias Experimentales , Pronóstico , Receptor IGF Tipo 1/metabolismo , Transducción de Señal , Análisis de Supervivencia
15.
J Neuroinflammation ; 20(1): 65, 2023 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-36890594

RESUMEN

BACKGROUND: Neuroinflammation plays a significant role in the progression of frontotemporal dementia (FTD). However, the association between peripheral inflammatory factors and brain neurodegeneration is poorly understood. We aimed to examine changes in peripheral inflammatory markers in patients with behavioural variant FTD (bvFTD) and explore the potential association between peripheral inflammation and brain structure, metabolism, and clinical parameters. METHODS: Thirty-nine bvFTD patients and 40 healthy controls were enrolled and underwent assessment of plasma inflammatory factors, positron emission tomography/magnetic resonance imaging, and neuropsychological assessments. Group differences were tested using Student's t test, Mann‒Whitney U test, or ANOVA. Partial correlation analysis and multivariable regression analysis were implemented using age and sex as covariates to explore the association between peripheral inflammatory markers, neuroimaging, and clinical measures. The false discovery rate was used to correct for the multiple correlation test. RESULTS: Plasma levels of six factors, including interleukin (IL)-2, IL-12p70, IL-17A, tumour necrosis superfamily member 13B (TNFSF/BAFF), TNFSF12 (TWEAK), and TNFRSF8 (sCD30), were increased in the bvFTD group. Five factors were significantly associated with central degeneration, including IL-2, IL-12p70, IL-17A, sCD30/TNFRSF8, and tumour necrosis factor (TNF)-α; the association between inflammation and brain atrophy was mainly distributed in frontal-limbic-striatal brain regions, whereas the association with brain metabolism was mainly in the frontal-temporal-limbic-striatal regions. BAFF/TNFSF13B, IL-4, IL-6, IL-17A and TNF-α were found to correlate with clinical measures. CONCLUSION: Peripheral inflammation disturbance in patients with bvFTD participates in disease-specific pathophysiological mechanisms, which could be a promising target for diagnosis, treatment, and monitoring therapeutic efficacy.


Asunto(s)
Demencia Frontotemporal , Enfermedad de Pick , Humanos , Demencia Frontotemporal/complicaciones , Demencia Frontotemporal/diagnóstico por imagen , Interleucina-17/metabolismo , Encéfalo/metabolismo , Enfermedad de Pick/patología , Imagen por Resonancia Magnética , Pruebas Neuropsicológicas , Inflamación/patología
16.
Clin Genet ; 104(3): 350-355, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37148197

RESUMEN

Studies focusing on octapeptide repeat alteration mutations in PRNP in Alzheimer's disease (AD) and frontotemporal dementia (FTD) cohorts have been rare. We aim to screen sporadic AD and FTD patients with unknown etiology for the octapeptide repeat insertions and deletions in PRNP. Two hundred and six individuals were screened for alterations to the repeat region in the PRNP gene, including 146 sporadic AD and 60 sporadic FTD patients. Our study showed a 1.5% (3/206) occurrence of the octapeptide repeat alteration mutations in PRNP in a Chinese cohort of sporadic dementia. One late-onset FTD patient and one early-onset AD patient each had a two-octapeptide repeat deletion in PRNP, while one early-onset AD patient had a five-octapeptide repeat insertion mutation. PRNP octapeptide repeat alteration mutations are present in sporadic AD and FTD patients. The genetic investigation for PRNP octapeptide repeat alteration mutations in sporadic dementia patients should be carried out in future clinical studies.


Asunto(s)
Enfermedad de Alzheimer , Demencia Frontotemporal , Priones , Humanos , Priones/genética , Priones/metabolismo , Proteínas Priónicas/genética , Demencia Frontotemporal/diagnóstico , Demencia Frontotemporal/genética , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/genética , Mutación
17.
Photodermatol Photoimmunol Photomed ; 39(6): 556-566, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37605539

RESUMEN

BACKGROUND: Skin photoaging is a condition caused by long-term exposure to ultraviolet irradiation, resulting in a variety of changes in the skin, such as capillary dilation, increased or absent pigmentation, dryness, sagging, and wrinkles. Stem cells possess a remarkable antioxidant capacity and the ability to proliferate, differentiate, and migrate, and their main mode of action is through paracrine secretion, with exosomes being the primary form of secretion. Stem cell-derived exosomes contain a variety of growth factors and cytokines and may have great potential to promote skin repair and delay skin ageing. METHODS: This review focuses on the mechanisms of UV-induced skin photoaging, the research progress of stem cell exosomes against skin photoaging, emerging application approaches and limitations in the application of exosome therapy. RESULT: Exosomes derived from various stem cells have the potential to prevent skin photoaging. CONCLUSION: The combination with novel materials may be a key step for their practical application, which could be an important direction for future basic research and practical applications.


Asunto(s)
Exosomas , Células Madre Mesenquimatosas , Envejecimiento de la Piel , Humanos , Exosomas/metabolismo , Piel/metabolismo
18.
Appl Opt ; 62(5): 1193-1199, 2023 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-36821217

RESUMEN

Lunar radiometric calibration is used to solve the problem of consistent radiometric calibration for multiple satellite platforms and remote sensors. However, the dark level fluctuates when observing the Moon with a short-wave infrared spectrometer, which seriously affects the accuracy of lunar radiation data. In this work, we propose a dynamic space-time dark level correction approach to address the fluctuation of the dark level. This method employs cold space signals in space and time dimensions to estimate the dark level for each frame individually and to reduce errors due to environmental variations. Experiments on lunar observations at multiple phase angles were conducted, and the dark level correction results demonstrate that our proposed method is effective even in the short-wave infrared, and is also superior to currently existing techniques. For a single-band (1700 nm) image of the full Moon, the mean background proportion of the proposed method is 1.00%, which is better than that of the static dark correction method (2.25%) and linear dark correction method (5.93%).

19.
Neurosurg Rev ; 46(1): 243, 2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37702883

RESUMEN

Previous studies have indicated that the small cerebellopontine angle (CPA) cistern plays a role in the pathogenesis of trigeminal neuralgia (TN), but they are likely not involved in TN associated with vertebrobasilar artery (VBA) compression because of its rarity. Forty-four patients with VBA-associated TN and 44 age-, sex-, and hypertension-matched TN patients without VBA compression (non-VBA-associated) were included. All patients underwent high-resolution MRI. The CPA cistern volumes were measured bilaterally. The presence of vertebrobasilar dolichoectasia (VBD) and laterality of the vertebrobasilar junction (VBJ) were observed. The CPA cistern volume on the affected side was smaller than the unaffected side (714.4 ± 372.8 vs 890.2 ± 462.2 mm3, p < 0.001) in non-VBA-associated TN patients, while VBA-associated TN patients show a larger CPA cistern on the affected side than the unffected side (1107.0 ± 500.5 vs 845.3 ± 314.8 mm3, p < 0.001). The prevalence of VBD was higher in patients with VBA-associated TN than in matched non-VBA-associated TN patients (90.9% vs 4.5%, p < 0.001). A positive correlation between the laterality of VBJ and the affected side was found in the VBA-associated TN group (p < 0.0001). Large CPA cistern may be a neuroradiological feature of VBA-associated TN, and most of the VBA-associated TN is accompanied by VBD. The presence of VBD and the lateral shift of VBJ may expand the CPA cistern by squeezing the surrounding tissue on the affected side and also increase the chance of VBA compression on the trigeminal nerve, resulting in the genesis of VBA-associated TN.


Asunto(s)
Hipertensión , Neuralgia del Trigémino , Humanos , Neuralgia del Trigémino/diagnóstico por imagen , Neuralgia del Trigémino/cirugía , Ángulo Pontocerebeloso/diagnóstico por imagen , Ángulo Pontocerebeloso/cirugía , Nervio Trigémino , Lateralidad Funcional
20.
Neurosurg Rev ; 46(1): 174, 2023 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-37442820

RESUMEN

When early lateral spread response (LSR) loss before decompression in HFS surgery happens, the value of intraoperative monitoring of LSR for locating neurovascular conflicts and confirming adequate decompression was considered to be reduced. This study aimed to identify preoperative parameters predicting early LSR loss and figure out the impact of early LSR loss on prognosis. Hemifacial spasm (HFS) patients who received microvascular decompression (MVD) under intraoperative electrophysiological monitoring during the period of March 2013-January 2021 were reviewed retrospectively. The patients were divided into two groups according to the disappearance of their LSR before or after decompression. Preoperative clinical and radiological predictors for early LSR loss were evaluated using logistic regression. The relationship between early LSR loss and surgical outcomes was statistically analyzed. A total of 523 patients were included in the study, and the disappearance of their LSR before decompression occurred in 129 patients. In the multivariate analysis, three independent factors predicting early LSR loss were identified: (1) smaller vessel compression; (2) milder nerve deviation; (3) lower posterior fossa crowdedness index (PFCI, calculated as hindbrain volume (HBV)/the posterior fossa volume (PFV) using 3D Slicer software). The median follow-up time was about five years, and no significant differences in the spasm relief and complication rates were found between the 2 groups. Smaller responsible vessels, milder nerve deviation, and more spacious posterior cranial fossa are associated with early LSR loss. However, early LSR loss seems to have no significant adverse effect on MVD outcomes in skilled hands.


Asunto(s)
Espasmo Hemifacial , Cirugía para Descompresión Microvascular , Humanos , Espasmo Hemifacial/cirugía , Resultado del Tratamiento , Estudios Retrospectivos , Pronóstico
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