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1.
Front Aging Neurosci ; 14: 827993, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547622

RESUMO

Background: Spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant hereditary ataxia, and, thus far, effective treatment remains low. Repetitive transcranial magnetic stimulation (rTMS) can improve the symptoms of spinal cerebellar ataxia, but the mechanism is unclear; in addition, whether any improvement in the symptoms is related to cerebellar metabolism has not yet been investigated. Therefore, the purpose of this study was to investigate the effects of low-frequency rTMS on local cerebellar metabolism in patients with SCA3 and the relationship between the improvement in the symptoms and cerebellar metabolism. Methods: A double-blind, prospective, randomized, sham-controlled trial was carried out among 18 SCA3 patients. The participants were randomly assigned to the real stimulation group (n = 9) or sham stimulation group (n = 9). Each participant in both the groups underwent 30 min of 1 Hz rTMS stimulation (a total of 900 pulses), differing only in terms of stimulator placement, for 15 consecutive days. To separately compare pre- and post-stimulation data (magnetic resonance spectroscopy (MRS) data and the International Cooperative Ataxia Rating Scale (ICARS) score) in the real and sham groups, paired-sample t-tests and Wilcoxon's signed-rank tests were used in the analyses. The differences in the ICARS and MRS data between the two groups were analyzed with independent t-tests and covariance. To explore the association between the changes in the concentration of cerebellar metabolism and ICARS, we applied Pearson's correlation analysis. Results: After 15 days of treatment, the ICARS scores significantly decreased in both the groups, while the decrease was more significant in the real stimulation group compared to the sham stimulation group (p < 0.001). The analysis of covariance further confirmed that the total ICARS scores decreased more dramatically in the real stimulation group after treatment compared to the sham stimulation group (F = 31.239, p < 0.001). The values of NAA/Cr and Cho/Cr in the cerebellar vermis, bilateral dentate nucleus, and bilateral cerebellar hemisphere increased significantly in the real stimulation group (p < 0.05), but no significant differences were found in the sham stimulation group (p > 0.05). The analysis of covariance also confirmed the greater change in the real stimulation group. This study also demonstrated that there was a negative correlation between NAA/Cr in the right cerebellar hemisphere and ICARS in the real stimulation group (r = - 0.831, p = 0.02). Conclusion: The treatment with rTMS over the cerebellum was found to induce changes in the cerebellar local metabolism and microenvironment in the SCA3 patients. The alterations may contribute to the improvement of the symptoms of ataxia in SCA3 patients.

2.
JACS Au ; 2(4): 853-864, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35557757

RESUMO

Photosensitized energy transfer (EnT) phenomena occur frequently in a variety of photophysical and photochemical processes and have traditionally been treated with the donor-acceptor distance-dependent Förster and Dexter models. However, incorrect arguments and formulae were employed by ignoring energy resonance conditions and the selection rules of the state-to-state transition in special cases, especially for the sensitive intramolecular EnT of lanthanide complexes. Herein, we proposed an innovative model of energy-degeneracy-crossing-controlled EnT, which can be experimentally confirmed by time-resolved two-dimensional photoluminescence measurements. The computationally determined energy resonance region provides the most effective channel to achieve metal-to-ligand EnT beyond the distance-dependent model and sensitively bifurcates into symmetry-allowed or -forbidden channels for some representative europium antenna complexes. The outcomes of the multidisciplinary treatment contribute to a complementary EnT model that can be tuned by introducing a phosphorescence modulator and altering the antenna-related parameters of the ligand-centered energy level of the 3ππ* state and its spin-orbit coupling for the 3ππ* → S0 * transition through mechanism-guided crystal engineering and should motivate further development of mechanistic models and applications.

3.
J Nutr Biochem ; : 109016, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35447319

RESUMO

Cholesterol and its oxidative derivative 27-hydroxycholesterol (27-OHC), synthesized by CYP27A1, play an important role in Alzheimer's disease (AD) and phosphorylation of tau might be partly responsible for its pathogenesis. To investigate whether cholesterol and 27-OHC affected learning and memory through autophagy-mediated phosphorylation of tau, male C57BL/6J mice were administrated with 2% cholesterol diet, CYP27A1-short-hairpin RNA (CYP27A1-shRNA) and 3-methyladenine (3-MA). The results show that dietary cholesterol induces learning and memory impairment by upregulating the expression of brain CYP27A1 and increasing the levels of 27-OHC and 24S-hydroxycholesterol (24S-OHC). The expressions of total-tau (t-tau), phosphorylated-tau (p-tau) protein, glycogen synthase kinase-3ß (GSK-3ß) and cyclin-dependent kinase 5 (CDK5) are also significantly upregulated in this group. In addition, reduced expressions of Beclin-1 protein and microtubule-associated protein 1 light chain 3 (LC3B) mRNA, over-expression of mammalian target of rapamycin (mTOR) protein suggest that autophagy is impaired during cholesterol burden. However, using of CYP27A1-shRNA remarkably downregulates the expression of brain CYP27A1. Decreased 27-OHC levels in serum and brain, lower expressions of t-tau and p-tau protein are observed in mice treated with CYP27A1-shRNA+2% cholesterol diet. Furthermore, 3-MA causes lower Beclin-1, higher mTOR and p62 on both gene and protein levels, while the expression of t-tau, p-tau, GSK-3ß and CDK5 are upregulated, demonstrating that impaired autophagy disturbs the clearance of tau. These findings suggest that dietary cholesterol induces the accumulation and phosphorylation of tau and the mechanism might be associated with impaired autophagy. And our results indicate 27-OHC might be an importance bridge between cholesterol and cognitive decline.

4.
Int J Mol Sci ; 23(8)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35457188

RESUMO

Dysregulation of cholesterol metabolism and its oxidative products-oxysterols-in the brain is known to be associated with neurodegenerative diseases. It is well-known that 27-hydroxycholesterol (27-OHC) and 24S-hydroxycholesterol (24S-OHC) are the main oxysterols contributing to the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanism of how 27-OHC and 24S-OHC cause cognitive decline remains unclear. To verify whether 27-OHC and 24S-OHC affect learning and memory by regulating immune responses, C57BL/6J mice were subcutaneously injected with saline, 27-OHC, 24S-OHC, 27-OHC+24S-OHC for 21 days. The oxysterols level and expression level of related metabolic enzymes, as well as the immunomodulatory factors were measured. Our results indicated that 27-OHC-treated mice showed worse learning and memory ability and higher immune responses, but lower expression level of interleukin-10 (IL-10) and interferon (IFN-λ2) compared with saline-treated mice, while 24S-OHC mice performed better in the Morris water maze test than control mice. No obvious morphological lesion was observed in these 24S-OHC-treated mice. Moreover, the expression level of interleukin-17A (IL-17A), granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage inflammatory protein 3α (MIP-3α) were significantly decreased after 24S-OHC treatment. Notably, compared with 27-OHC group, mice treated with 27-OHC+24S-OHC showed higher brain 24S-OHC level, accompanied by increased CYP46A1 expression level while decreased CYP7B1, retinoic acid-related orphan receptor gamma t (RORγt) and IL-17A expression level. In conclusion, our study indicated that 27-OHC is involved in regulating the expression of RORγt, disturbing Th17/Treg balance-related immune responses which may be associated with the learning and memory impairment in mice. In contrast, 24S-OHC is neuroprotective and attenuates the neurotoxicity of 27-OHC.


Assuntos
Interleucina-17 , Oxisteróis , Animais , Hidroxicolesteróis/metabolismo , Hidroxicolesteróis/farmacologia , Interleucina-17/genética , Camundongos , Camundongos Endogâmicos C57BL , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Linfócitos T Reguladores/metabolismo
5.
Oxid Med Cell Longev ; 2022: 8622388, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242280

RESUMO

Chronic inflammatory pain seriously affects patients' quality of life because of a paucity of effective clinical treatments caused, at least in part, by lack of full understanding of the underlying mechanisms. miRNAs are known to be involved in inflammatory pain via silencing or degrading of target mRNA in the cytoplasm. The present study provides a novel mechanism by which miRNA-22 positively regulates metal-regulatory transcription factor 1 (Mtf1) in the nuclei of neurons in the dorsal horn of the spinal cord. We found that miRNA-22 was significantly increased in the dorsal horn of mice with either inflammatory pain induced by plantar injection of complete Freund's adjuvant (CFA) or neuropathic pain induced by unilateral sciatic nerve chronic constrictive injury (CCI). Knocking down or blocking miRNA-22 alleviated CFA-induced mechanical allodynia and heat hyperalgesia, whereas overexpressing miRNA-22 produced pain-like behaviors. Mechanistically, the increased miRNA-22 binds directly to the Mtf1 promoter to recruit RNA polymerase II and elevate Mtf1 expression. The increased Mtf1 subsequently enhances spinal central sensitization, as evidenced by increased expression of p-ERK1/2, GFAP, and c-Fos in the dorsal horn. Our findings suggest that the miRNA-22-Mtf1 signaling axis in the dorsal horn plays a critical role in the induction and maintenance of inflammatory pain. This signaling pathway may be a promising therapeutic target in inflammatory pain.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Hiperalgesia/metabolismo , MicroRNAs/metabolismo , Neuralgia/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Células do Corno Posterior/metabolismo , Nervo Isquiático/lesões , Transdução de Sinais/genética , Fatores de Transcrição/metabolismo , Regulação para Cima/genética , Animais , Núcleo Celular/metabolismo , Proteínas de Ligação a DNA/genética , Adjuvante de Freund/efeitos adversos , Hiperalgesia/genética , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Masculino , Camundongos , MicroRNAs/genética , Neuralgia/induzido quimicamente , Neuralgia/genética , Traumatismos dos Nervos Periféricos/genética , RNA Interferente Pequeno/genética , Fatores de Transcrição/genética , Transfecção/métodos
6.
BMC Geriatr ; 22(1): 197, 2022 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-35279091

RESUMO

BACKGROUND: Joint contractures and degenerative osteoarthritis are the most common joint diseases in the elderly population, can lead to limited mobility in elderly individuals, can exacerbate symptoms such as pain, stiffness, and disability, and can interfere with social participation and quality of life, thus affecting mental health. However, relevant studies on this topic are very limited. This study describes the associations of joint contracture categories and sites in elderly residents in long-term care facilities with their quality of life, activities, and participation. METHODS: Elderly individuals with joint contractures who were residents in long-term care facilities were recruited. The World Health Organization (WHO) Quality of Life and the WHO Disability Assessment Schedule 2.0 were used to survey the participants. Correlations, multiple linear regressions, and multiple analyses of variance, with joint contractures as the response variable, were used in the statistical analysis. RESULTS: The final statistical analysis included 232 participants. The explanatory power of contracture sites on activities and participation had a moderate strength of association (η2 = .113). Compared with elderly residents with joint contractures and osteoarthritis isolated to the upper limbs, those with joint contractures and osteoarthritis in both the upper and lower limbs had significantly worse activity and participation limitations. No significant differences in activity and participation were found between elderly residents with joint contractures affecting only the upper limbs and those with joint contractures affecting only the lower limbs (F1,226 = 2.604 and F1,226 = 0.674, nonsignificant). Osteoarthritis had the greatest impact on activity limitations and participation restrictions among elderly residents with joint contractures affecting both the upper and lower limbs (F1,226 = 6.251, p = .014). CONCLUSIONS: Elderly residents in long-term care facilities belonging to minority groups, with a history of stroke, and with osteoarthritis are at a high risk of developing activity limitations and participation restrictions. Moreover, compared with other contraction sites, regardless of osteoarthritis, joint contractures affecting both the upper and lower limbs were associated with the greatest activity limitations and participation restrictions. TRIAL REGISTRATION: This study has been registered in the Chinese Clinical Trial Registry, registration number and date: ChiCTR2000039889 (13/11/2020).


Assuntos
Contratura , Osteoartrite , Idoso , Contratura/diagnóstico , Contratura/epidemiologia , Contratura/psicologia , Estudos Transversais , Humanos , Assistência de Longa Duração , Casas de Saúde , Qualidade de Vida
7.
Artigo em Inglês | MEDLINE | ID: mdl-35198034

RESUMO

BACKGROUND: There are still controversies about the curative effect of vitamin C in treating HIE, and its mechanism of action is not entirely clear. This study is designed to explore the potential molecular mechanism of vitamin C in treating neonatal hypoxic ischemic encephalopathy (HIE). METHODS: The effect targets of vitamin C and the pathogenic targets of neonatal HIE were obtained via retrieval of public databases to screen out the molecular targets of vitamin C acting on neonatal HIE. Gene Ontology (GO) functional annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the main targets. Vitamin C and the optimum target structural components are subjected to molecular docking and molecular dynamics simulation analysis via computer software so as to verify their binding activity and stability. RESULT: Based on 16 overlapping targets of vitamin C and HIE, seven main targets were identified in this study. According to GO and KEGG analysis, molecular functions (top 25 items) and signal pathways (21 items) related to inflammatory reaction, immune response, and cell transcriptional control may be potential pathways for vitamin C to treat neonatal HIE. Molecular docking and molecular dynamics simulation were adopted to definitively determine the 4 optimum core target spots. CONCLUSION: The efficacy of vitamin C on HIE is involved in the immunoregulation and inflammation-related functional processes and signal pathways. These molecular mechanisms, including core targets, will contribute to the clinical practice of neonatal HIE in the future.

8.
Front Neurol ; 13: 833908, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185776

RESUMO

BACKGROUND: Spinocerebellar ataxia type 3 (SCA3) is one of the most common hereditary neurodegenerative diseases. Postural control dysfunction is the main symptom of SCA3, and the proprioceptive system is a critical sensory component of postural control. Accordingly, proprioception quantification assessment is necessary in monitoring the progression of SCA3. OBJECTIVE: We aimed to quantitatively assess lower limb proprioception and investigate the relationship between proprioception and clinical characteristics in patients with SCA3. METHODS: A total of 80 patients with SCA3 and 62 health controls were recruited, and their lower limb proprioception was measured using the Pro-kin system. Clinical characteristics of the SCA3 patients were collected. Multivariable linear regression was used to investigate potential affected factors for lower limb proprioception. RESULTS: We found that the patients with SCA3 experience poorer lower limb proprioception characterized by significant impairment in the average trace error (ATE) and time to carry out the test time execution (TTE) compared to controls (P < 0.05). Moreover, there were significant differences in TTE between the right and left lower limbs (P < 0.05) of the patients. Regression analyses revealed that increasing age at onset (AAO) predicts poorer lower limb proprioception for both ATE (ß = 2.006, P = 0.027) and TTE (ß = 1.712, P = 0.043) and increasing disease duration predicts poorer lower limb proprioception for ATE (ß = 0.874, P = 0.044). AAO (ß = 0.328, P = 0.019) along with the expanded alleles (ß = 0.565, P = 0.000) could affect the severity of ataxia. By contrast, ATE (ß = 0.036, P = 0.800) and TTE (ß = -0.025, P = 0.862) showed no significant predictors. CONCLUSIONS: Lower limb proprioception in patients with SCA3 is significantly impaired when compared to healthy controls. Increasing AAO and disease duration are related to impaired lower limb proprioception.

9.
J Clin Med ; 11(3)2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35159987

RESUMO

Primary Sjögren's syndrome (SjS) is an inflammatory autoimmune disorder which targets the lacrimal and salivary glands, resulting in glandular dysfunction. Currently, the immune drivers of SjS remain poorly understood and peripheral biomarkers of disease are lacking. The present study therefore sought to investigate the immune cell constituents of the SjS peripheral blood, and to assess the role of the BTLA/HVEM/CD160 co-stimulatory network by characterizing expression within the periphery. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood of n = 10 patients with SjS and n = 10 age- and sex-matched healthy control donors. Cells were divided and stained with three panels of antibodies, allowing assessment of T, B, and myeloid cell subsets, and measurement of BTLA, HVEM, and CD160 surface expression by flow cytometry. We identified distinct alterations in proportions of peripheral T, B, and myeloid cell types in SjS compared with healthy controls. Expression of BTLA/CD160/HVEM and frequency of BTLA/CD160/HVEM-expressing cells were significantly altered in peripheral SjS lymphocytes. The proportion of T cells co-expressing BTLA/HVEM and CD160/HVEM were significantly reduced in SjS. We found decreased BTLA and HVEM levels on peripheral B and T cells of SjS patients, and decreased BTLA/HVEM and CD160/HVEM co-expression, demonstrating dysregulation of the BTLA/HVEM axis in the peripheral blood of SjS patients. These results indicate the potential of targeting the BTLA-HVEM axis for the treatment of SjS.

10.
Mol Omics ; 18(3): 196-205, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-34982085

RESUMO

MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes) is a progressive neurodegenerative disease caused by pathogenic mitochondrial DNA variants. The pathogenic mechanism of MELAS remains enigmatic due to the exceptional clinical heterogeneity and the obscure genotype-phenotype correlation among MELAS patients. To gain insights into the pathogenic signature of MELAS, we designed a comprehensive strategy integrating proteomics and metabolomics in patient-derived dermal fibroblasts harboring the ultra-rare MELAS pathogenic variant m.14453G>A, specifically affecting the mitochondrial respiratory complex I. Global proteomics was achieved by data-dependent acquisition (DDA) and verified by data-independent acquisition (DIA) using both Spectronaut and the recently launched MaxDIA platforms. Comprehensive metabolite coverage was achieved for both polar and nonpolar metabolites in both reverse phase and HILIC LC-MS/MS analyses. Our proof-of-principle MELAS study with multi-omics integration revealed OXPHOS dysregulation with a predominant deficiency of complex I subunits, as well as alterations in key bioenergetic pathways, glycolysis, tricarboxylic acid cycle, and fatty acid ß-oxidation. The most clinically relevant discovery is the downregulation of the arginine biosynthesis pathway, likely due to blocked argininosuccinate synthase, which is congruent with the MELAS cardinal symptom of stroke-like episodes and its current treatment by arginine infusion. In conclusion, we demonstrated an integrated proteomic and metabolomic strategy for patient-derived fibroblasts, which has great clinical potential to discover therapeutic targets and design personalized interventions after validation with a larger patient cohort in the future.


Assuntos
Síndrome MELAS , Doenças Neurodegenerativas , Acidente Vascular Cerebral , Arginina , Cromatografia Líquida , Humanos , Síndrome MELAS/diagnóstico , Síndrome MELAS/genética , Síndrome MELAS/patologia , Metabolômica , Doenças Neurodegenerativas/tratamento farmacológico , Proteômica , Acidente Vascular Cerebral/tratamento farmacológico , Espectrometria de Massas em Tandem
11.
Adv Healthc Mater ; 11(8): e2102439, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34859964

RESUMO

The boosting exploitation of graphene oxide (GO) increases exposure risk to human beings. However, as primary defender in the first immune line, neutrophils' mechanism of defensive behavior toward GO remains unclear. Herein, we discovered that neutrophils recognize and defensively degrade GO in a lateral dimension dependent manner. The micrometer-sized GO (mGO) induces NETosis by releasing neutrophil extracellular traps (NETs), while nanometer-sized GO (nGO) elicits neutrophil degranulation. The two neutrophils' defensive behaviors are accompanied with generation of reactive oxygen species and activation of p-ERK and p-Akt kinases. However, mGO-induced NETosis is NADPH oxidase (NOX)-independent while nGO-triggered degranulation is NOX-dependent. Furthermore, myeloperoxidase (MPO) is determinant mediator despite distinct neutrophil phenotypes. Neutrophils release NETs comprising of MPO upon activated with mGO, while MPO is secreted via nGO-induced degranulation. Moreover, the binding energy between MPO and GO is calculated to be 69.8728 kJ mol-1 , indicating that electrostatic interactions mainly cause the spontaneous binding process. Meanwhile, the central enzymatic biodegradation occurs at oxygenic active sites and defects on GO. Mass spectrometry analysis deciphers the degradation products are biocompatible molecules like flavonoids and polyphenols. This study provides fundamental evidence and practical guidance for nanotechnology based on GO, including vaccine adjuvant, implantable devices, and energy storage.


Assuntos
Armadilhas Extracelulares , Luta Romana , Grafite , Óxido de Magnésio/metabolismo , Neutrófilos , Espécies Reativas de Oxigênio/metabolismo
12.
Brain Imaging Behav ; 16(1): 379-388, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34417969

RESUMO

Spinocerebellar ataxias type 3 (SCA3) patients are clinically characterized by progressive cerebellar ataxia combined with degeneration of the cerebellum. Previous neuroimaging studies have indicated ataxia severity associated with cerebellar atrophy using univariate methods. However, whether cerebellar atrophy patterns can be used to quantitatively predict ataxia severity in SCA3 patients at the individual level remains largely unexplored. In this study, a group of 66 SCA3 patients and 58 healthy controls were included. Disease duration and ataxia assessment, including the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS), were collected for SCA3 patients. The high-resolution T1-weighted MRI was obtained, and cerebellar grey matter (GM) was extracted using a spatially unbiased infratentorial template toolbox for all participants. We investigated the association between the pattern of cerebellar grey matter (GM) loss and ataxia assessment in SCA3 by using a multivariate machine learning technique. We found that the application of RVR allowed quantitative prediction of both SARA scores (leave-one-subject-out cross-validation: correlation = 0.56, p-value = 0.001; mean squared error (MSE) = 20.51, p-value = 0.001; ten-fold cross-validation: correlation = 0.52, p-value = 0.001; MSE = 21.00, p-value = 0.001) and ICARS score (leave-one-subject-out cross-validation: correlation = 0.59, p-value = 0.001; MSE = 139.69, p-value = 0.001; ten-fold cross-validation: correlation = 0.57, p-value = 0.001; MSE = 145.371, p-value = 0.001) with statistically significant accuracy. These results provide proof-of-concept that ataxia severity in SCA3 patients can be predicted by the alteration pattern of cerebellar GM using multi-voxel pattern analysis.


Assuntos
Ataxia Cerebelar , Doença de Machado-Joseph , Ataxia , Ataxia Cerebelar/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Humanos , Doença de Machado-Joseph/diagnóstico por imagem , Doença de Machado-Joseph/genética , Imageamento por Ressonância Magnética
13.
Inorg Chem ; 60(24): 18990-19000, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34851093

RESUMO

Single-molecule magnets (SMMs) are expected to be promising candidates for the applications of high-density information storage materials and quantum information processing. Lanthanide SMMs have attracted considerable interest in recent years due to their excellent performance. It has always been interesting but not straightforward to study the relaxation and blocking mechanisms by embedding 3d ions into 4f SMMs. Here we report a family of air-stable 3d-4f ion-pair compounds, YFe (1), DyCr (2), DyFe (3), DyCo (4), and Dy0.04Y0.96Fe (5), composed of pentagonal bipyramidal (D5h) LnIII cations and transition metallocyanate anions. The ion-pair nature makes the dipole-dipole interactions almost the only component of the magnetic interactions that can be clarified and analytically resolved under proper approximation. Therefore, this family provides an intuitive opportunity to investigate the effects of 3d-4f and 4f-4f magnetic interactions on the behavior of site-resolved 4f SMMs. Dynamic magnetic measurements of 1 under a 4 kOe external field reveal slow magnetic relaxation originating from the isolated [FeIII]LS (S = 1/2) ions. Under zero dc field, compounds 2-5 show similar magnetic relaxation processes coming from the separated pentagonal bipyramidal (D5h) DyIII ions with high Orbach barriers of 592(5), 596(4), 595(3), and 606(4) K, respectively. Comparatively, both compounds 3 and 5 exhibit two distinct relaxation processes, respectively from the [FeIII]LS and DyIII [Ueff = 596(4) K for 3 and 610(7) K for 5] ions, under a 4 kOe dc field. The dipolar interactions between the neighboring TMIII (TM = transition metal, CrIII or [FeIII]LS) and DyIII ions were revealed to have little effect on the thermal relaxation in compounds 2, 3, and 5, or the coexistence of the two separate relaxation processes in compounds 3 and 5 under a 4 kOe dc field, but they significantly affect the quantum tunneling of magnetization and the magnetic hysteresis behavior of 2 and 3 at low temperatures compared to those of 4.

14.
Front Bioeng Biotechnol ; 9: 755506, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765593

RESUMO

Introduction: Cerebral palsy (CP) is the leading cause of childhood-onset physical disability. Children with CP often have impaired upper limb (UL) function. Constraint-induced therapy (CIT) is one of the most effective UL interventions for children with unilateral CP. However, concerns about CIT for children have been repeatedly raised due to frustration caused by restraint of the child's less-affected UL and lack of motivation for the intensive protocol. Virtual reality (VR), which can mitigate the disadvantages of CIT, potentially can be used as an alternative mediator for implementing CIT. Therefore, we developed a VR-based CIT program for children with CP using the Kinect system. Aims: The feasibility of the Kinect-based CIT program was evaluated for children with unilateral CP using a two-phase study design. Materials and Methods: In phase 1, ten children with unilateral CP were recruited. To confirm the achievement of the motor training goals, maximal UL joint angles were evaluated during gameplay. To evaluate children's perceptions of the game, a questionnaire was used. In phase 2, eight children with unilateral CP were recruited and received an 8 weeks Kinect-based CIT intervention. Performance scores of the game and outcomes of the box and block test (BBT) were recorded weekly. Results: In phase 1, results supported that the design of the program was CIT-specific and was motivational for children with unilateral CP. In phase 2, game performance and the BBT scores began showing stable improvements in the fifth week of intervention. Conclusion: It suggested the Kinect-based CIT program was beneficial to the motor function of the affected UL for children with unilateral CP. According to the results of this feasibility study, larger and controlled effectiveness studies of the Kinect-based CIT program can be conducted to further improve its clinical utility. Clinical Trial Registration: ClinicalTrials.gov, NCT02808195; Comparative effectiveness of a Kinect-based unilateral arm training system vs. CIT for children with CP.

15.
J Neurol ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34783886

RESUMO

OBJECTIVE: To investigate whether neurite orientation dispersion and density imaging (NODDI) could provide the added value for detecting brain microstructural alterations in the preclinical stage of Machado-Joseph disease/spinocerebellar ataxia type 3 (MJD/SCA3) compared with MRI morphometry and diffusion tensor imaging (DTI). METHODS: Twenty preclinical MJD/SCA3 patients and 21 healthy controls were enrolled. Three b values DWI and 3D T1-weighted images were acquired at 3.0 T. Tract-based spatial statistics (TBSS) approach was used to investigate the white matter (WM) alterations in the DTI metrics and NODDI metrics. Gray matter-based spatial statistics (GBSS) approach was used to investigate the grey matter (GM) alterations in the NODDI metrics. Voxel-based morphometry (VBM) approach was performed on the 3D T1-weighted images. The relationship between the cytosine-adenine-guanine (CAG) repeat length and brain microstructural alterations of preclinical MJD/SCA3 was identified. RESULTS: Compared with healthy controls, the preclinical MJD/SCA3 patients showed decreased FA and NDI as well as increased MD, AD, and RD in the WM of cerebellum and brainstem (corrected P < 0.05), and decreased NDI in the GM of cerebellar vermis (corrected P < 0.05). The CAG repeat length in preclinical MJD/SCA3 patients was negatively correlated with the reduced FA and NDI of the infratentorial WM and the reduced NDI of the cerebellum, and positively with the increased MD and RD of the infratentorial WM. CONCLUSIONS: NOODI can provide novel quantitative microstructural changes in MJD/SCA3 carriers, expanding our understanding of the gray and white matter (axons and dendrites) degeneration in this frequent ataxia syndrome.

16.
Western Pac Surveill Response J ; 12(3): 82-87, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703640

RESUMO

OBJECTIVE: Contact tracing has been used in China and several other countries in the WHO Western Pacific Region as part of the COVID-19 response. We describe COVID-19 cases and the number of contacts traced and quarantined per case as part of COVID-19 emergency public health response activities in China. METHODS: We abstracted publicly available, online aggregated data published in daily COVID-19 situational reports by China's National Health Commission and provincial health commissions between 20 January and 29 February 2020. The number of new contacts traced by report date was computed as the difference between total contacts traced in consecutive reports. A proxy for the number of contacts traced per case was computed as the number of new contacts traced divided by the number of new cases. RESULTS: During the study period, China reported 80 968 new COVID-19 cases and 659 899 contacts. In Hubei Province, there were 67 608 cases and 264 878 contacts, representing 83% and 40% of the total, respectively. Non-Hubei provinces reported tracing 1.5 times more contacts than Hubei Province; the weekly number of contacts traced per case was also higher in non-Hubei provinces than in Hubei Province and increased from 17.2 in epidemiological week 4 to 115.7 in epidemiological week 9. DISCUSSION: More contacts per case were reported from areas and periods with lower COVID-19 case counts. With other non-pharmaceutical interventions used in China, contact tracing and quarantining large numbers of potentially infected contacts probably contributed to reducing SARS-CoV-2 transmission.

17.
Sci Rep ; 11(1): 20955, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34697312

RESUMO

This study aimed to examine the reliabilities (test-retest reliability and measurement error), construct validity, and the interpretability (minimal clinically important difference) of the Box and Block Test (BBT) to interpret test scores precisely for children with UCP. A total of 100 children with UCP were recruited and 50 children from the whole sample assessed the BBT twice within 2-week interval. The BBT, the Melbourne Assessment 2, the Bruininks-Oseretsky Test of Motor Proficiency, 2nd Edition, and the Pediatric Motor Activity Log Revised were measured before and immediately after a 36-h intensive neurorehabilitation intervention. Measurement properties of the BBT were performed according to the COnsensus-based Standards for the selection of health Measurement INstruments checklist. The test-retest reliability of the BBT was high (intraclass correlation coefficient = 0.98). The measurement error estimated by the MDC95 value was 5.95. Construct validity was considered good that 4 of 4 (100%) hypotheses were confirmed. The interpretability estimated by the MCID ranged from 5.29 to 6.46. The BBT is a reliable and valid tool for children with UCP. For research and clinical applications, an improvement of seven blocks on the BBT is recommended as an indicator of statistically significant and clinically important change.


Assuntos
Paralisia Cerebral/reabilitação , Reabilitação Neurológica/métodos , Adolescente , Criança , Avaliação da Deficiência , Feminino , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Resultado do Tratamento
18.
BMC Neurol ; 21(1): 402, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34666706

RESUMO

BACKGROUND: Charcot-Marie-Tooth (CMT) disease is a group of inherited peripheral neuropathies, which are subdivided into demyelinating and axonal forms. Biallelic mutations in POLR3B are the well-established cause of hypomyelinating leukodystrophy, which is characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. To date, only one study has reported the demyelinating peripheral neuropathy phenotype caused by heterozygous POLR3B variants. CASE PRESENTATION: A 19-year-old male patient was referred to our hospital for progressive muscle weakness of the lower extremities. Physical examination showed muscle atrophy, sensory loss and deformities of the extremities. Nerve conduction studies and electromyography tests revealed sensorimotor demyelinating polyneuropathy with secondary axonal loss. Trio whole-exome sequencing revealed a de novo variant in POLR3B (c.3137G > A). CONCLUSIONS: In this study, we report the case of a Chinese patient with a de novo variant in POLR3B (c.3137G > A), who manifested demyelinating CMT phenotype without additional neurological or extra-neurological involvement. This work is the second report on POLR3B-related CMT.


Assuntos
Doença de Charcot-Marie-Tooth , Adulto , Doença de Charcot-Marie-Tooth/genética , China , Heterozigoto , Humanos , Masculino , Mutação/genética , Fenótipo , RNA Polimerase III , Adulto Jovem
19.
Front Aging Neurosci ; 13: 707958, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512309

RESUMO

Background: Nutrients are associated with cognitive function, but limited research studies have systematically evaluated on multi-domain cognitive function. The aim of this study was to investigate the effect and mechanism of specific nutrient on multi-domain cognitive function, and provide nutrition guidance for improving cognitive function. Methods: Participants were selected based on a multicenter prospective study on middle-aged and older adults in China. Global cognitive function was evaluated by the Mini-Mental State Examination (MMSE). Nutrients intake was assessed according to food frequency questionnaire and China Food Composition Database, and principal component analysis was performed to extract nutrient patterns. Associations between specific nutrients and cognitive function were assessed using log-binomial regression. Restricted cubic spline was used to illustrate the dose-response relationship of nutrients with multi-domain cognitive function. Mediation analysis was used to determine the mechanism of nutrients in cognitive function. Results: Four nutrient patterns were identified (vitamin-mineral, protein-carbohydrate, fatty acid-vitamin E, and cholesterol-vitamin B12), and only a nutrient pattern rich in cholesterol and vitamin B12 was found associated with cognitive function (RR = 0.891, 95%CI = 0.794-0.999). In multi-domain cognitive function, dietary cholesterol and vitamin B12 were related to better performance of visual memory function (P = 0.034, P = 0.02). In dose-response relationship, it suggested a U-shaped association between vitamin B12 and MMSE (P = 0.02) within a certain range. Conclusions: Dietary intake rich in cholesterol and vitamin B12 was associated with better cognitive function, and vitamin B12 had a U-shaped dose-response relation with MMSE. Thus, ensuring moderate cholesterol and vitamin B12intake may be an advisable strategy to improve cognitive function in middle-aged and older adults. Clinical Trial Registration: EMCOA, ChiCTR-OOC-17011882, Registered 5th, July 2017-Retrospectively registered, http://www.medresman.org/uc/project/projectedit.aspx?proj=2610.

20.
J Nutr ; 151(12): 3865-3873, 2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34510220

RESUMO

BACKGROUND: Several studies have reported that dietary and serum concentrations of vitamin D and cholesterol are correlated with mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, little is known about whether 25 hydroxyvitamin D [25(OH)D], lipids, and oxysterols are related to cognitive function. OBJECTIVE: This study sought to explore the relations between 25(OH)D, lipids, oxysterols, and cognitive function. METHODS: In this study, about 209 MCI patients and 209 age- and gender-matched healthy controls were recruited from the Shanxi province of China (49.5% male; median [IQR] age: 63 [59-66] y). Serum concentrations of 25(OH)D, lipids, and oxysterols were measured using ultra-performance LC-MS. Cognitive performance was determined via comprehensive mental, verbal, and auditory cognitive tests. Dietary information was collected using a semiquantitative FFQ and 3 consecutive days of 24-h dietary recalls. Logistic regression analyses, Spearman's correlation, and partial correlation analyses were used to explore correlation between the variables. RESULTS: Participants with vitamin D deficiency [serum 25(OH)D <20.0 ng/mL] were 3 times more likely to develop MCI compared to those with adequate vitamin D (≥30 ng/mL) concentrations. The AUC of 25(OH)D was 0.72 and the cut-off was 16.5 ng/mL (sensitivity:  50.3%,  specificity: 84.4%). Serum 25(OH)D concentrations were negatively correlated with total cholesterol (TC) (r = -0.19, P = 0.02), LDL-cholesterol (r = -0.17, P = 0.04), and 24S,25-epoxycholesterol (24S,25-epoxy-CHO) (r = -0.21, P = 0.01). Conversely, the Montreal Cognitive Assessment (MoCA) (r = 0.185, P < 0.001) and symbol digit modalities test (SDMT) (r = 0.11, P = 0.03) scores were positively correlated with serum 25(OH)D concentrations. CONCLUSION: The study identified significant differences in serum 25(OH)D concentrations between MCI patients and cognitive healthy controls, and there was a correlation between serum concentrations of 25(OH)D, lipids, and oxysterols and cognitive impairment among people. This study was registered at the Chinese Clinical Trial Registry as ChiCTR1900025452.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Deficiência de Vitamina D , Idoso , Calcifediol , Disfunção Cognitiva/etiologia , Feminino , Homeostase , Humanos , Masculino , Pessoa de Meia-Idade , Vitamina D , Deficiência de Vitamina D/complicações
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