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1.
J Transl Med ; 21(1): 352, 2023 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-37245044

RESUMEN

BACKGROUND: The cerebellum plays key roles in the pathology of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), but the way in which these conditions affect how the cerebellum communicates with the rest of the brain (its connectome) and associated genetic correlates remains largely unknown. METHODS: Combining multimodal MRI data from 208 MS patients, 200 NMOSD patients and 228 healthy controls and brain-wide transcriptional data, this study characterized convergent and divergent alterations in within-cerebellar and cerebello-cerebral morphological and functional connectivity in MS and NMOSD, and further explored the association between the connectivity alterations and gene expression profiles. RESULTS: Despite numerous common alterations in the two conditions, diagnosis-specific increases in cerebellar morphological connectivity were found in MS within the cerebellar secondary motor module, and in NMOSD between cerebellar primary motor module and cerebral motor- and sensory-related areas. Both diseases also exhibited decreased functional connectivity between cerebellar motor modules and cerebral association cortices with MS-specific decreases within cerebellar secondary motor module and NMOSD-specific decreases between cerebellar motor modules and cerebral limbic and default-mode regions. Transcriptional data explained > 37.5% variance of the cerebellar functional alterations in MS with the most correlated genes enriched in signaling and ion transport-related processes and preferentially located in excitatory and inhibitory neurons. For NMOSD, similar results were found but with the most correlated genes also preferentially located in astrocytes and microglia. Finally, we showed that cerebellar connectivity can help distinguish the three groups from each other with morphological connectivity as predominant features for differentiating the patients from controls while functional connectivity for discriminating the two diseases. CONCLUSIONS: We demonstrate convergent and divergent cerebellar connectome alterations and associated transcriptomic signatures between MS and NMOSD, providing insight into shared and unique neurobiological mechanisms underlying these two diseases.


Asunto(s)
Conectoma , Esclerosis Múltiple , Neuromielitis Óptica , Humanos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/genética , Neuromielitis Óptica/diagnóstico por imagen , Neuromielitis Óptica/genética , Neuromielitis Óptica/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen por Resonancia Magnética , Cerebelo/diagnóstico por imagen , Cerebelo/patología
2.
J Neurol Neurosurg Psychiatry ; 94(1): 31-37, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36216455

RESUMEN

OBJECTIVE: To evaluate the clinical significance of deep learning-derived brain age prediction in neuromyelitis optica spectrum disorder (NMOSD) relative to relapsing-remitting multiple sclerosis (RRMS). METHODS: This cohort study used data retrospectively collected from 6 tertiary neurological centres in China between 2009 and 2018. In total, 199 patients with NMOSD and 200 patients with RRMS were studied alongside 269 healthy controls. Clinical follow-up was available in 85 patients with NMOSD and 124 patients with RRMS (mean duration NMOSD=5.8±1.9 (1.9-9.9) years, RRMS=5.2±1.7 (1.5-9.2) years). Deep learning was used to learn 'brain age' from MRI scans in the healthy controls and estimate the brain age gap (BAG) in patients. RESULTS: A significantly higher BAG was found in the NMOSD (5.4±8.2 years) and RRMS (13.0±14.7 years) groups compared with healthy controls. A higher baseline disability score and advanced brain volume loss were associated with increased BAG in both patient groups. A longer disease duration was associated with increased BAG in RRMS. BAG significantly predicted Expanded Disability Status Scale worsening in patients with NMOSD and RRMS. CONCLUSIONS: There is a clear BAG in NMOSD, although smaller than in RRMS. The BAG is a clinically relevant MRI marker in NMOSD and RRMS.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/diagnóstico por imagen , Esclerosis Múltiple/diagnóstico por imagen , Estudios Retrospectivos , Estudios de Cohortes , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Encéfalo/diagnóstico por imagen
3.
Chem Rec ; 23(11): e202300126, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37435961

RESUMEN

Azobenzene-containing small molecules and polymers are functional photoswitchable molecules to form supramolecular nanomaterials for various applications. Recently, supramolecular nanomaterials have received enormous attention in material science because of their simple bottom-up synthesis approach, understandable mechanisms and structural features, and batch-to-batch reproducibility. Azobenzene is a light-responsive functional moiety in the molecular design of small molecules and polymers and is used to switch the photophysical properties of supramolecular nanomaterials. Herein, we review the latest literature on supramolecular nano- and micro-materials formed from azobenzene-containing small molecules and polymers through the combinatorial effect of weak molecular interactions. Different classes including complex coacervates, host-guest systems, co-assembled, and self-assembled supramolecular materials, where azobenzene is an essential moiety in small molecules, and photophysical properties are discussed. Afterward, azobenzene-containing polymers-based supramolecular photoresponsive materials formed through the host-guest approach, polymerization-induced self-assembly, and post-polymerization assembly techniques are highlighted. In addition to this, the applications of photoswitchable supramolecular materials in pH sensing, and CO2 capture are presented. In the end, the conclusion and future perspective of azobenzene-based supramolecular materials for molecular assembly design, and applications are given.

4.
Mult Scler ; 28(5): 707-717, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34379008

RESUMEN

BACKGROUND: Hippocampal involvement may differ between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). OBJECTIVE: To investigate the morphometric, diffusion and functional alterations in hippocampus in MS and NMOSD and the clinical significance. METHODS: A total of 752 participants including 236 MS, 236 NMOSD and 280 healthy controls (HC) were included in this retrospective multi-center study. The hippocampus and subfield volumes, fractional anisotropy (FA) and mean diffusivity (MD), amplitude of low frequency fluctuation (ALFF) and degree centrality (DC) were analyzed, and their associations with clinical variables were investigated. RESULTS: The hippocampus showed significantly lower volume, FA and greater MD in MS compared to NMOSD and HC (p < 0.05), while no abnormal ALFF or DC was identified in any group. Hippocampal subfields were affected in both diseases, though subiculum, presubiculum and fimbria showed significantly lower volume only in MS (p < 0.05). Significant correlations between diffusion alterations, several subfield volumes and clinical variables were observed in both diseases, especially in MS (R = -0.444 to 0.498, p < 0.05). FA and MD showed fair discriminative power between MS and HC, NMOSD and HC (AUC > 0.7). CONCLUSIONS: Hippocampal atrophy and diffusion abnormalities were identified in MS and NMOSD, partly explaining how clinical disability and cognitive impairment are differentially affected.


Asunto(s)
Esclerosis Múltiple , Neuromielitis Óptica , Hipocampo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple/diagnóstico por imagen , Neuromielitis Óptica/diagnóstico por imagen , Estudios Retrospectivos
5.
J Org Chem ; 86(23): 16699-16706, 2021 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-34761932

RESUMEN

The usefulness of 14N NMR spectroscopy was highly underestimated compared with 15N NMR, which usually required tedious and expensive 15N-labeling manipulations. It is of great significance to make the 14N NMR spectroscopy convenient and useful considering 14N nuclei's high natural abundance of 99.6%. Herein, lots of efforts have been made to generalize routine 14N NMR to characterize nitrogen-containing species by tuning the balance between the solubility and viscosity of the samples. Satisfactory 14N NMR spectra of more than 60 nitrogen-containing compounds have been recorded, and the chemical shifts and the peaks' full width at half-maxima of more than 10 nitrogen-based functionalities have been summarized. Successful monitoring of the ortho-selective nitration of aniline has been demonstrated using the 14N NMR protocol developed in this paper, which will help realize the visualization of nitration processes in the industry.

6.
Pharm Biol ; 59(1): 1216-1232, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34493162

RESUMEN

CONTEXT: Modified BuShenYiQi formula (M-BYF) is derived from BuShenYiQi formula, used for the treatment of allergic asthma. The exact effect and mechanism of M-BYF on the improvement of asthma remain unclear. OBJECTIVE: We investigated the mechanism underlying the therapeutic effect of M-BYF on allergic asthma. MATERIALS AND METHODS: The asthma model was established in female BALB/c mice that were sensitized and challenged with ovalbumin (OVA). Mice in the treated groups were orally treated once a day with M-BYF (7, 14 and 28 g/kg/d) or dexamethasone before OVA challenge. Control and Model group received saline. Pathophysiological abnormalities and percentages of lung type 2 innate lymphoid cells (ILC2s) and Th9 cells were measured. Expression levels of type 2 cytokines and transcription factors required for these cells function and differentiation were analysed. Expression of vasoactive intestinal polypeptide (VIP)-VPAC2 signalling pathway-related proteins, and percentages of VIP expressing (VIP+) cells and VPAC2, CD90 co-expressing (VPAC2+CD90+) cells were detected. RESULTS: M-BYF alleviated airway hyperresponsiveness, inflammation, mucus hypersecretion and collagen deposition in asthmatic mice. M-BYF down-regulated percentages of ILC2s and Th9 cells with lower expression of GATA3, PU.1 and IRF4, reduced IL-5, IL-13, IL-9 and VIP production. The decrease in the expression of VIP-VPAC2 signalling pathway and percentages of VIP+ cells, VPAC2+CD90+ cells were observed after M-BYF treatment. The LD50 value of M-BYF was higher than 90 g/kg. DISCUSSION AND CONCLUSIONS: M-BYF alleviated experimental asthma by negatively regulating ILC2s and Th9 cells and the VIP-VPAC2 signalling pathway. These findings provide the theoretical basis for future research of M-BYF in asthma patient population.


Asunto(s)
Antiasmáticos/farmacología , Asma/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Hipersensibilidad Respiratoria/tratamiento farmacológico , Animales , Asma/inmunología , Dexametasona/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/administración & dosificación , Femenino , Inmunidad Innata/efectos de los fármacos , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Ratones , Ratones Endogámicos BALB C , Receptores de Tipo II del Péptido Intestinal Vasoactivo/metabolismo , Hipersensibilidad Respiratoria/inmunología , Transducción de Señal/efectos de los fármacos , Antígenos Thy-1/inmunología , Péptido Intestinal Vasoactivo/metabolismo
7.
BMC Neurosci ; 21(1): 37, 2020 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-32933478

RESUMEN

BACKGROUND: Although previous studies have shown that intra-network abnormalities in brain functional networks are correlated with clinical/cognitive impairment in multiple sclerosis (MS), there is little information regarding the pattern of causal interactions among cognition-related resting-state networks (RSNs) in different disease stages of relapsing-remitting MS (RRMS) patients. We hypothesized that abnormalities of causal interactions among RSNs occurred in RRMS patients in the acute and remitting phases. METHODS: Seventeen patients in the acute phases of RRMS, 24 patients in the remitting phases of RRMS, and 23 appropriately matched healthy controls participated in this study. First, we used group independent component analysis to extract the time courses of the spatially independent components from all the subjects. Then, the Granger causality analysis was used to investigate the causal relationships among RSNs in the spectral domain and to identify correlations with clinical indices. RESULTS: Compared with the patients in the acute phase of RRMS, patients in the remitting phase of RRMS showed a significantly lower expanded disability status scale, modified fatigue impact scale scores, and significantly higher paced auditory serial addition test (PASAT) scores. Compared with healthy subjects, during the acute phase, RRMS patients had significantly increased driving connectivity from the right executive control network (rECN) to the anterior salience network (aSN), and the causal coefficient was negatively correlated with the PASAT score. During the remitting phase, RRMS patients had significantly increased driving connectivity from the rECN to the aSN and from the rECN to the visuospatial network. CONCLUSIONS: Together with the disease duration (mean disease duration < 5 years) and relatively better clinical scores than those in the acute phase, abnormal connections, such as the information flow from the rECN to the aSN and the rECN to the visuospatial network, might provide adaptive compensation in the remitting phase of RRMS.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Red Nerviosa/fisiopatología , Adolescente , Adulto , Anciano , Mapeo Encefálico , Causalidad , Evaluación de la Discapacidad , Función Ejecutiva , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Red Nerviosa/diagnóstico por imagen , Análisis de Componente Principal , Descanso , Adulto Joven
8.
Pulm Pharmacol Ther ; 65: 102005, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33636365

RESUMEN

Allergic asthma is a common airway inflammatory disease and mainly caused by abnormal immune responses to allergens and viruses. The precise mechanisms of airway inflammation and airway hyper-responsiveness (AHR) are still not completely understood. CD4+ helper T cells (Th cells) serve as critical regulators of allergic immunity. The imbalance between T helper 9 (Th9) cells and forkhead box protein 3 (Foxp3)+ regulatory T (Treg) cells may contribute to airway inflammation in asthma. Epimedin C, a dominant compound isolated from Herba Epimedii, has shown anti-inflammatory effects and the immunoregulatory activity, such as increase of lymphocyte proliferation. However, the protective role of epimedin C in an experimental model of ovalbumin (OVA)-induced allergic airway inflammation and the underlying mechanism remain unknown. Female BALB/c mice were sensitized by intraperitoneal injection (i.p.) of OVA plus aluminum hydroxide (Alum) and subsequently challenged with an aerosol of 3% OVA in saline. Mice were treated with different concentrations of epimedin C (20 mg/kg/d, 40 mg/kg/d, 80 mg/kg/d) for 4 weeks. Experimental endpoints were evaluated via the analysis of AHR to acetyl-ß-methacholine (Mch), differential inflammatory cell counts, concentrations of cytokines interleukin-9 (IL-9), IL-4 and IL-10 in bronchoalveolar lavage fluid (BALF), serum OVA-specific IgE level, as well as airway inflammation, mucus secretion and collagen deposition in mice. Mechanistically, we investigated the percentages of Th9 cells and Treg cells, as well as mRNA levels of IL-9 and transcription factor Foxp3 in lungs. Furthermore, the proteins expression of nuclear factor-κB (NF-κB) family members p105/p50, RelA, p100/p52 and RelB, as well as mitogen-activated protein kinase (MAPK) family members extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 MAPK was detected. Epimedin C dose-dependently attenuated AHR, airway inflammation, mucus hypersecretion and collagen deposition in OVA-induced murine asthma model. The expression levels of IL-9, IL-4 and OVA-specific IgE were significantly decreased while IL-10 was increased by epimedin C. We further confirmed that epimedin C decreased the percentage of lung Th9 cells with lower mRNA expression of IL-9 and increased the percentage of lung Treg cells with higher mRNA expression of Foxp3. In addition, epimedin C dose-dependently decreased the protein levels of p52, RelB, phosphorylation of ERK1/2 and p38 MAPK which are pivotal to the development of Th9 cells and Treg cells. Collectively, epimedin C could inhibit pathophysiological features of asthma by reconstruction of the balance between Th9 cells and Treg cells through regulation of the noncanonical NF-κB p52/RelB pathway and MAPKs activation. These findings suggest epimedin C as a potential remedy for inflammatory airway diseases.


Asunto(s)
Asma , Linfocitos T Reguladores , Animales , Asma/tratamiento farmacológico , Líquido del Lavado Bronquioalveolar , Citocinas , Modelos Animales de Enfermedad , Femenino , Flavonoides , Inflamación , Pulmón , Ratones , Ratones Endogámicos BALB C , Ovalbúmina , Linfocitos T Colaboradores-Inductores
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(12): 1261-1266, 2020 Dec.
Artículo en Zh | MEDLINE | ID: mdl-33327995

RESUMEN

OBJECTIVE: To study the application value of whole exome sequencing (WES) in critically ill neonates with inherited diseases. METHODS: A total of 66 critically ill neonates with suspected inherited diseases or unclear clinical diagnosis who were admitted to the neonatal intensive care unit were enrolled as subjects. The clinical data of the neonates were collected, and venous blood samples were collected from the neonates and their parents for WES. The clinical manifestations of the neonates were observed to search for related pathogenic gene mutations. RESULTS: Among the 66 critically ill neonates with suspected inherited diseases or unclear clinical diagnosis (34 boys and 32 girls), 14 (21%) were found to have gene mutations by WES. One neonate had no gene mutation detected by WES but was highly suspected of pigment incontinence based on clinical manifestations, and multiplex ligation-dependent probe amplification detected a heterozygous deletion mutation in exons 4-10 of the IKBKG gene. Among the 15 neonates with gene mutations, 10 (67%) had pathogenic gene mutation, 1 (7%) was suspected of pathogenic gene mutation, and 4 (27%) had gene mutations with unknown significance. Among the 15 neonates, 13 underwent chromosome examination, and only 1 neonate was found to have chromosome abnormality. CONCLUSIONS: Chromosome examination cannot be used as a diagnostic method for inherited diseases, and WES detection technology is an important tool to find inherited diseases in critically ill neonates with suspected inherited diseases or unclear clinical diagnosis; however WES technology has some limitation and it is thus necessary to combine with other sequencing methods to achieve an early diagnosis.


Asunto(s)
Enfermedad Crítica , Secuenciación del Exoma , Enfermedades Genéticas Congénitas/diagnóstico , Exones , Femenino , Enfermedades Genéticas Congénitas/genética , Heterocigoto , Humanos , Quinasa I-kappa B/genética , Recién Nacido , Masculino , Mutación
10.
Environ Sci Technol ; 53(1): 146-156, 2019 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-30500174

RESUMEN

The initial deposition kinetics of colloidal MnO2 on three representative surfaces in aquatic systems (i.e., silica, magnetite, and alumina) in NaNO3 solution were investigated in the presence of model constituents, including humic acid (HA), a polysaccharide (alginate), and a protein (bovine serum albumin (BSA), using laboratory quartz crystal microbalance with dissipation monitoring equipment (QCM-D). The results indicated that the deposition behaviors of MnO2 colloids on three surfaces were in good agreement with classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. Critical deposition concentrations (CDC) were determined to be 15.5 mM NaNO3 and 9.0 mM NaNO3 when colloidal MnO2 was deposited onto silica and magnetite, respectively. Both HA and alginate could largely retard the deposition of MnO2 colloids onto three selected surfaces due to steric repulsion, and HA was more effective in decreasing the deposition rate relative to alginate. However, the presence of BSA can provide more attractive deposition site and thus lead to greater deposition behavior of MnO2 colloids onto surfaces. The dissipative properties of the deposited layer were also influenced by surface type, electrolyte concentration, and organic matter characteristics. Overall, these results provide insights into the deposition behavior of MnO2 colloids on environmental surfaces and have significant implications for predicting the transport potential of common MnO2 colloids in natural environments and engineered systems.


Asunto(s)
Sustancias Húmicas , Compuestos de Manganeso , Cinética , Óxidos , Dióxido de Silicio , Propiedades de Superficie
11.
J Phys Chem A ; 122(1): 8-15, 2018 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-29220171

RESUMEN

Nitrogen-rich compounds such as tetrazoles are widely used as candidates in gas-generating agents. However, the details of the differentiation of the two isomers of disubstituted tetrazoles are rarely studied, which is very important information for designing advanced materials based on tetrazoles. In this article, pairs of 2,5- and 1,5-disubstituted tetrazoles were carefully designed and prepared for study on their thermal decomposition behavior. Also, the substitution fashion of 2,5- and 1,5- and the substituents at C-5 position were found to affect the endothermic or exothermic properties. This is for the first time to the best of our knowledge that the thermal decomposition properties of different tetrazoles could be tuned by substitution ways and substitute groups, which could be used as a useful platform to design advanced materials for temperature-dependent rockets. The aza-Claisen rearrangement was proposed to understand the endothermic decomposition behavior.

13.
Neuroreport ; 35(7): 476-485, 2024 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-38597326

RESUMEN

The objective of this study is to explore the relationship between the glymphatic system and alterations in the structure and function of the brain in white matter hyperintensity (WMH) patients. MRI data were collected from 27 WMH patients and 23 healthy controls. We calculated the along perivascular space (ALPS) indices, the anterior corner distance of the lateral ventricle, and the width of the third ventricle for each subject. The DPABISurf tool was used to calculate the cortical thickness and cortical area. In addition, data processing assistant for resting-state fMRI was used to calculate regional homogeneity, degree centrality, amplitude low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), and voxel-mirrored homotopic connectivity (VMHC). In addition, each WMH patient was evaluated on the Fazekas scale. Finally, the correlation analysis of structural indicators and functional indicators with bilateral ALPS indices was investigated using Spearman correlation analysis. The ALPS indices of WMH patients were lower than those of healthy controls (left: t = -4.949, P < 0.001; right: t = -3.840, P < 0.001). This study found that ALFF, fALFF, regional homogeneity, degree centrality, and VMHC values in some brain regions of WMH patients were alternated (AlphaSim corrected, P < 0.005, cluster size > 26 voxel, rmm value = 5), and the cortical thickness and cortical area of WMH patients showed trend changes (P < 0.01, cluster size > 20 mm2, uncorrected). Interestingly, we found significantly positive correlations between the left ALPS indices and degree centrality values in the superior temporal gyrus (r = 0.494, P = 0.009, P × 5 < 0.05, Bonferroni correction). Our results suggest that glymphatic system impairment is related to the functional centrality of local connections in patients with WMH. This provides a new perspective for understanding the pathological mechanisms of cognitive impairment in the WMH population.


Asunto(s)
Sistema Glinfático , Sustancia Blanca , Humanos , Sistema Glinfático/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Imagen por Resonancia Magnética/métodos
14.
Adv Mater ; : e2405731, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38857110

RESUMEN

The recycling and utilization of precious metals have emerged as a critical research focus in advancing the development of the circular economy. Among numerous methods for recovering precious metals such as gold, adsorbents with both high adsorption selectivity and capacity have become key technologies. This article incorporated the N-phenylpyrrolidine into a flexible porous polynorbornene backbone to create a class of distinctive porous organic polymers, named BIT-POP-14-BIT-POP-17. Through a reductive capture mechanism, the reductive adsorption sites of N-phenylpyrrolidine coordinate selectively with precious metals, the reduced metal is captured by the hierarchically porous polymers with flexible backbone. This approach leads to remarkable gold recovery efficiency, achieving a record of 2321 mg g-1 at ambient conditions, and 3020 mg g-1 under UV light, surpassing the theoretical limit. The porous polymers are filled in a column for a continuous uptake of gold from waste printed circuit boards (PCBs), showing recovery efficiency toward gold as high as 95% after 84 h. Overall, this work offers a new perspective on designing novel adsorbents for precious metal recovery, providing inspiration for researchers to explore novel adsorption modes and contribute to the advancement of the circular economy.

15.
Sci Rep ; 14(1): 4199, 2024 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-38378887

RESUMEN

Approximately 36% of patients with neuromyelitis optica spectrum disorders (NMOSD) suffer from severe visual and motor disability (blindness or light perception or unable to walk) with abnormalities of whole-brain functional networks. However, it remains unclear how whole-brain functional networks and their dynamic properties are related to clinical disability in patients with NMOSD. Our study recruited 30 NMOSD patients (37.70 ± 11.99 years) and 45 healthy controls (HC, 41.84 ± 11.23 years). The independent component analysis, sliding-window approach and graph theory analysis were used to explore the static strength, time-varying and topological properties of large-scale functional networks and their associations with disability in NMOSD. Compared to HC, NMOSD patients showed significant alterations in dynamic networks rather than static networks. Specifically, NMOSD patients showed increased occurrence (fractional occupancy; P < 0.001) and more dwell times of the low-connectivity state (P < 0.001) with fewer transitions (P = 0.028) between states than HC, and higher fractional occupancy, increased dwell times of the low-connectivity state and lower transitions were related to more severe disability. Moreover, NMOSD patients exhibited altered small-worldness, decreased degree centrality and reduced clustering coefficients of hub nodes in dynamic networks, related to clinical disability. NMOSD patients exhibited higher occurrence and more dwell time in low-connectivity states, along with fewer transitions between states and decreased topological organizations, revealing the disrupted communication and coordination among brain networks over time. Our findings could provide new perspective to help us better understand the neuropathological mechanism of the clinical disability in NMOSD.


Asunto(s)
Personas con Discapacidad , Trastornos Motores , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/patología , Imagen por Resonancia Magnética , Encéfalo/patología
16.
J Neurol ; 271(6): 3595-3609, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38558149

RESUMEN

BACKGROUND: Spinal cord and brain atrophy are common in neuromyelitis optica spectrum disorder (NMOSD) and relapsing-remitting multiple sclerosis (RRMS) but harbor distinct patterns accounting for disability and cognitive impairment. METHODS: This study included 209 NMOSD and 304 RRMS patients and 436 healthy controls. Non-negative matrix factorization was used to parse differences in spinal cord and brain atrophy at subject level into distinct patterns based on structural MRI. The weights of patterns were obtained using a linear regression model and associated with Expanded Disability Status Scale (EDSS) and cognitive scores. Additionally, patients were divided into cognitive impairment (CI) and cognitive preservation (CP) groups. RESULTS: Three patterns were observed in NMOSD: (1) Spinal Cord-Deep Grey Matter (SC-DGM) pattern was associated with high EDSS scores and decline of visuospatial memory function; (2) Frontal-Temporal pattern was associated with decline of language learning function; and (3) Cerebellum-Brainstem pattern had no observed association. Patients with CI had higher weights of SC-DGM pattern than CP group. Three patterns were observed in RRMS: (1) DGM pattern was associated with high EDSS scores, decreased information processing speed, and decreased language learning and visuospatial memory functions; (2) Frontal-Temporal pattern was associated with overall cognitive decline; and (3) Occipital pattern had no observed association. Patients with CI trended to have higher weights of DGM and Frontal-Temporal patterns than CP group. CONCLUSION: This study estimated the heterogeneity of spinal cord and brain atrophy patterns in NMOSD and RRMS patients at individual level, and evaluated the clinical relevance of these patterns, which may contribute to stratifying participants for targeted therapy.


Asunto(s)
Atrofia , Encéfalo , Imagen por Resonancia Magnética , Neuromielitis Óptica , Médula Espinal , Humanos , Neuromielitis Óptica/patología , Neuromielitis Óptica/diagnóstico por imagen , Femenino , Masculino , Adulto , Atrofia/patología , Persona de Mediana Edad , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Médula Espinal/patología , Médula Espinal/diagnóstico por imagen , Disfunción Cognitiva/etiología , Disfunción Cognitiva/patología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/fisiopatología , Esclerosis Múltiple Recurrente-Remitente/patología , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Sustancia Gris/patología , Sustancia Gris/diagnóstico por imagen
17.
Molecules ; 18(4): 3906-16, 2013 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-23549297

RESUMEN

The synthesis of stable guanofosfocin analogues has attracted considerable attention in the past 15 years. Several guanofosfocin analogues mimicking the three constitutional elements of mannose, ribose, and guanine were designed and synthesized. Interest in ether-linked pseudodisaccharides and 8-alkylated guanines is increasing, due to their potential applications in life science. In this article, a novel guanofosfocin analogue 6, an ether-linked pseudodisaccharide connected α-C-glycosidically to an 8-alkylated guanine, was synthesized in a 10-longest linear step sequence from known diol 13, resulting in an overall yield of 26%. The key steps involve the ring-opening of cyclic sulfate 8 by alkoxide generated from 7 and a reductive cyclization of 4-N-acyl-2,4-diamino-5-nitrosopyrimidine 19 to form compound 6.


Asunto(s)
Disacáridos/síntesis química , Manosa/análogos & derivados , Alquilación , Ciclización , Guanina/química , Manosa/síntesis química , Pirimidinas/química , Relación Estructura-Actividad
18.
Molecules ; 18(6): 6723-33, 2013 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-23749160

RESUMEN

Protected L-homoDMDP en-8 and its C-6 epimer en-7 were prepared through two different pathways starting from the vinylpyrrolidine en-9. Based on the NMR and X-ray analysis, the stereochemistry of homoDMDP at C-6 was confirmed to be consistent with reported data. Compounds en-7 and en-8 are general intermediates for the synthesis of a series of 6-C-alkylated DMDP-related natural products, such as broussonetine G, homoDMDP-7-O-apioside, homoDMDP-7-O-b-D-xyloside and so on.


Asunto(s)
Productos Biológicos/química , Piperazinas/química , Piridazinas/química , Productos Biológicos/síntesis química , Estructura Molecular , Piperazinas/síntesis química , Piridazinas/síntesis química , Estereoisomerismo
19.
Acta Crystallogr Sect E Struct Rep Online ; 69(Pt 6): o924-5, 2013 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-23795093

RESUMEN

In the title mol-ecule, C26H17N3O2, both indole ring systems are essentially planar, with maximum deviations of 0.019 (2) and 0.033 (1) Šfor the N atoms, and form dihedral angles of 34.40 (9) and 45.06 (8)° with the essentially planar pyrrole ring [maximum deviation = 0.020 (2) Å]. The dihedral angle between the two indole ring systems is 58.78 (6)°. In the crystal, mol-ecules are connected by pairs of N-H⋯O hydrogen bonds, forming inversion dimers and generating R 2 (2)(8) rings. Weak π-π stacking inter-actions, with a centroid-centroid distance of 3.983 (2) Å, are also observed.

20.
ACS Macro Lett ; 12(10): 1358-1364, 2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37733801

RESUMEN

Porous organic polymers (POPs) have demonstrated promising task-specific applications due to their structure designability and thus functionality. Herein, an unusual 3,4-polymerization on 1,2,5-trisubstituted pyrroles has been developed to give linear polypyrrole-3,4 in high efficiency, with Mn of 20000 and PDI of 1.7. This novel polymerization technique was applied to prepare a series of polypyrrole-based POPs (PY-POP-1-4), which exhibited high BET surface areas (up to 762 m2 g-1) with a meso-micro-supermicro hierarchically porous structure. Furthermore, PY-POPs were doped in the mixed matrix membranes based on the polysulfone matrix to enhance the gas permeability and gas pair selectivity, with H2/N2 selectivity up to 84.6 and CO2/CH4 and CO2/N2 selectivity up to 46.8 and 39.6.

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