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1.
Polymers (Basel) ; 16(13)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-39000614

RESUMO

Soil degradation threatens agricultural productivity and food supply, leading to hunger issues in some developing regions. To address this challenge, we developed a low-cost, highly efficient, and long-term stable soil improvement method. We chose polyvinyl alcohol (PVA), a commercially available polymer that is safe and non-degradable, to serve as a soil adhesive. We mixed PVA solution into the soil and applied a drying treatment to enhance the bonding between PVA and the soil, achieving highly water-stable soil. This PVA-stabilized soil exhibits low bulk density, high porosity, and high permeability, making it an ideal substrate for planting. In a germination test, the PVA-stabilized soil revealed a higher germination rate and growth rate compared to those of the non-treated soil. We believe this simple and efficient soil improvement method can restore degraded soil and contribute to sustainable agriculture.

3.
J Hum Genet ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866925

RESUMO

BACKGROUND: Intronic GAA repeat expansion ([GAA] ≥250) in FGF14 is associated with the late-onset neurodegenerative disorder, spinocerebellar ataxia 27B (SCA27B, GAA-FGF14 ataxia). We aim to determine the prevalence of the GAA repeat expansion in FGF14 in Chinese populations presenting late-onset cerebellar ataxia (LOCA) and evaluate the characteristics of tandem repeat inheritance, radiological features and sympathetic nerve involvement. METHODS: GAA-FGF14 repeat expansion was screened in an undiagnosed LOCA cohort (n = 664) and variations in repeat-length were analyzed in families of confirmed GAA-FGF14 ataxia patients. Brain magnetic resonance imaging (MRI) was used to evaluate the radiological feature in GAA-FGF14 ataxia patients. Clinical examinations and sympathetic skin response (SSR) recordings in GAA-FGF14 patients (n = 16) were used to quantify sympathetic nerve involvement. RESULTS: Two unrelated probands (2/664) were identified. Genetic screening for GAA-FGF14 repeat expansion was performed in 39 family members, 16 of whom were genetically diagnosed with GAA-FGF14 ataxia. Familial screening revealed expansion of GAA repeats in maternal transmissions, but contraction upon paternal transmission. Brain MRI showed slight to moderate cerebellar atrophy. SSR amplitude was lower in GAA-FGF14 patients in pre-symptomatic stage compared to healthy controls, and further decreased in the symptomatic stage. CONCLUSIONS: GAA-FGF14 ataxia was rare among Chinese LOCA cases. Parental gender appears to affect variability in GAA repeat number between generations. Reduced SSR amplitude is a prominent feature in GAA-FGF14 patients, even in the pre-symptomatic stage.

4.
Hepatology ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836646

RESUMO

Liver diseases contribute to ~2 million deaths each year and account for 4% of all deaths globally. Despite various treatment options, the management of liver diseases remains challenging. Physical exercise is a promising nonpharmacological approach to maintain and restore homeostasis and effectively prevent and mitigate liver diseases. In this review, we delve into the mechanisms of physical exercise in preventing and treating liver diseases, highlighting its effects on improving insulin sensitivity, regulating lipid homeostasis, and modulating immune function. In addition, we evaluate the impact of physical exercise on various liver diseases, including liver ischemia/reperfusion injury, cardiogenic liver disease, metabolic dysfunction-associated steatotic liver disease, portal hypertension, cirrhosis, and liver cancer. In conclusion, the review underscores the effectiveness of physical exercise as a beneficial intervention in combating liver diseases.

5.
QJM ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676661
6.
Langmuir ; 40(13): 6786-6805, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38503426

RESUMO

Traditional heterogeneous catalysts are affected in the catalytic hydrogenation of PS by the scale effect, viscosity effect, adhesion effect, and conformational effect, resulting in poor activity and stability. Monolithic Pd-CNTs@FN catalysts could eliminate or weaken the impact of these negative effects. We grew nitrogen-doped carbon nanotubes (NCNTs) on monolithic-foamed nickel (FN) and investigate their growth mechanism. Meanwhile, the feasibility of using the NCNTs@FN carrier for PS hydrogenation reaction was also verified. The growth of NCNTs on FN can be divided into 3 stages: initial growth stage, stable growth stage, and supersaturation stage. Finally, a three-layer structure of NCNT layer, dense carbon layer, and FN skeleton is formed. Two types of structures, nickel-doped carbon nanotubes (NiCNTs) and C-Ni alloy, are formed by combining C and Ni, while four nitrogen-doped structures, NPD, NPR, NG, and NO, are formed by C and N. The prepared carrier exhibited an extremely outstanding specific surface area (2.829 × 106 cm2/g) and strength (no NCNTs falling off after 24 h 500 rpm agitation), as well as high catalytic activity for PS hydrogenation after loaded with Pd (2.13 ± 0.95 nm), with a TOF of up to 27.6 gPS/(gPd•h). After 8 repetitions of the catalyst, there was no significant decrease in activity. This proves the excellent performance of Pd-NCNTs@FN in polymer hydrogenation reactions, laying a solid foundation for further research on the mechanism of NCNTs promoting PS hydrogenation and regulating the growth of NCNTs.

7.
J Clin Anesth ; 94: 111415, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38394922

RESUMO

STUDY OBJECTIVE: To identify whether adding ketamine to the local anesthetics (LA) in the regional anesthesia could prolong the duration of analgesia. DESIGN: A Systematic review and meta-analysis of randomized controlled trials. SETTING: The major dates were obtained in the operating room and the postoperative recovery ward. PATIENTS: A total of 1011 patients at ASA physical status I and II were included in the analysis. Procedure performed including cesarean section, orthopedic, radical mastectomy, urological or lower abdominal surgery and intracavitary brachytherapy implants insertion. INTERVENTIONS: After an extensive search of the electronic database, patients received regional anesthesia combined or not combined general anesthesia and with or without adding ketamine to LA were included in the analysis. The regional anesthesia includes spinal anesthesia, brachial plexus block, pectoral nerve block, transversus abdominis plane block and femoral and sciatic nerve block. MEASUREMENT: The primary outcome was the duration of analgesia. Secondary outcomes were the duration and onset time of motor and sensory block as well as the ketamine-related adverse effect. Data are expressed in mean differences in continuous data and odds ratios (OR) for dichotomous data with 95% confidence intervals. The risk of bias of the included studies was evaluated using the revised Cochrane risk of bias tool for randomized trials. The quality of evidence for each outcome was rated according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Working Group system. MAIN RESULT: Twenty randomized controlled trials were included in the analysis. When ketamine was used as an adjuvant to LA, the duration of analgesia could be prolonged(172.21 min, 95% CI, 118.20 to 226.22; P<0.00001, I2 = 98%), especially in the peripheral nerve block(366.96 min, 95% CI, 154.19 to 579.74; P = 0.0007, I2 = 98%). Secondary outcomes showed ketamine could prolong the duration of sensory block(29.12 min, 95% CI, 10.22 to 48.01; P = 0.003, I2 = 96%) but no effect on the motor block(6.94 min, 95% CI,-2.65 to 16.53;P = 0.16, I2 = 84%), the onset time of motor and sensory block (motor onset time, -1.17 min, 95% CI, -2.67 to 0.34; P = 0.13, I2 = 100%; sensory onset time, -0.33 min, 95% CI,-0.87 to 0.20; P = 0.23, I2 = 96%) as well as the ketamine-related adverse effect(OR, 1.97, 95% CI,0.93 to 4.17;P = 0.08, I2 = 57%). CONCLUSION: This study indicates that ketamine could be an ideal adjuvant to local anesthetics regardless of the types of anesthesia. Overall, the quality of the evidence is low.


Assuntos
Anestesia por Condução , Bloqueio do Plexo Braquial , Neoplasias da Mama , Ketamina , Feminino , Humanos , Gravidez , Anestésicos Locais/efeitos adversos , Anestésicos Locais/uso terapêutico , Bloqueio do Plexo Braquial/métodos , Cesárea , Ketamina/efeitos adversos , Ketamina/uso terapêutico , Mastectomia , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Macromol Rapid Commun ; 45(2): e2300467, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37863475

RESUMO

Conductive polymer hydrogels are vital in strain sensors, yet achieving high resilience and toughness is a challenge. This study employs a prestretch method to engineer a tough conductive polymer hydrogel with sufficient resilience. Initially, a blend film of polyvinylalcohol (PVA) and ethylene-vinyl alcohol copolymer (EVOH) is prepared through solution casting, followed by a swelling process to form a PVA-EVOH hydrogel. This hydrogel, with PVA crystallites as crosslinking points, exhibits high toughness. The hydrogel is then immersed in pyrrole and ferric chloride solutions for in-situ polymerization of polypyrrole (PPy), creating a conductive PPy/PVA-EVOH hydrogel. Finally, a 200% prestretch is applied, breaking short chains within the network, eliminating energy dissipation at low strains. This results in a hydrogel with a 100% elastic deformation range, while maintaining high fracture toughness (1700 J m-2 ). The prestretched PPy/PVA-EVOH hydrogel functions as a strain sensor with low hysteresis, providing consistent strain measurements during loading and unloading. This outperforms the non-prestretched sample, which shows inconsistent responses between stretching and releasing.


Assuntos
Polímeros , Resiliência Psicológica , Hidrogéis , Pirróis , Álcool de Polivinil , Condutividade Elétrica
9.
Neurosci Bull ; 40(2): 147-156, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37847448

RESUMO

The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation. This stereoelectroencephalography (SEEG) study investigated how the dorsolateral prefrontal cortex (DLPFC) interacts with the hippocampus in the online processing of sequential information. Twenty patients with epilepsy (eight women, age 27.6 ± 8.2 years) completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus. Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise (random trials) than to maintain ordered lines (ordered trials) before recalling the orientation of a particular line. First, the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC (3-10 Hz). In particular, the hippocampal theta power increase correlated with the memory precision of line orientation. Second, theta phase coherences between the DLPFC and hippocampus were enhanced for ordering, especially for more precisely memorized lines. Third, the theta band DLPFC → hippocampus influence was selectively enhanced for ordering, especially for more precisely memorized lines. This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.


Assuntos
Epilepsia , Memória de Curto Prazo , Adulto , Feminino , Humanos , Adulto Jovem , Hipocampo , Rememoração Mental , Córtex Pré-Frontal , Ritmo Teta , Masculino
10.
J Genet Genomics ; 51(2): 184-196, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38159879

RESUMO

CGG repeat expansions in LOC642361/NUTM2B-AS1 have recently been identified as a cause of oculopharyngeal myopathy with leukoencephalopathy. However, since only three patients from a single family were reported, it remains unknown whether their clinicopathological features are typical for CGG repeat expansions in LOC642361/NUTM2B-AS1. Here, using repeat-primed-polymerase chain reaction and long-read sequencing, we identify 12 individuals from 3 unrelated families with CGG repeat expansions in LOC642361/NUTM2B-AS1, typically presenting with oculopharyngodistal myopathy. The CGG repeat expansions range from 161 to 669 repeat units. Most of the patients present with ptosis, restricted eye movements, dysphagia, dysarthria, and diffuse limb muscle weakness. Only one patient shows T2-weighted hyperintensity in the cerebellar white matter surrounding the deep cerebellar nuclei on brain magnetic resonance imaging. Muscle biopsies from three patients show a myopathic pattern and rimmed vacuoles. Analyses of muscle biopsies suggest that CGG repeat expansions in LOC642361/NUTM2B-AS1 may deleteriously affect aggrephagic capacity, suggesting that RNA toxicity and mitochondrial dysfunction may contribute to pathogenesis. Our study thus expands the phenotypic spectrum for the CGG repeat expansion of LOC642361/NUTM2B-AS1 and indicates that this genetic variant typically manifests as oculopharyngodistal myopathy with chronic myopathic changes with rimmed vacuoles and filamentous intranuclear inclusions in muscle fibers.


Assuntos
Doenças Musculares , Distrofias Musculares , Humanos , Debilidade Muscular , Doenças Musculares/genética , Doenças Musculares/patologia , Distrofias Musculares/genética , Distrofias Musculares/patologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-38082626

RESUMO

Although Freezing of gait (FOG) is one of the most frustrating phenomena for people with Parkinson's Disease (PD), especially in their advanced stage, it is one of the least explained syndromes. The current studies only showed beta oscillations existed in frontal cortex-basal ganglia networks. Further studies need to be carried out. However, simultaneously recording neuro-electrophysiologic signals during walking is always a challenge, especially for Electroencephalogram (EEG) and Local Field Potential (LFP). This paper demonstrated a Virtual Reality (VR) based system which can trigger FOG and record biological signals at the same time. Moreover, the utilisation of VR will significantly decrease space requirements. It will provide a safer and more convenient evaluation environment for future participants. One participant with PD helped to validate the feasibility of the system. The result showed that both EEG and LFP could be recorded at the same time with trigger markers. This system design can be used to trigger freezing episodes in the controlled environment, differentiate subtypes of gait difficulties, and identify neural signatures associated with freezing episodes.Clinical relevance - This paper proposed a VR-based comprehensive FOG neuro-electrophysiologic evaluation system for people with PD. It had the advantages of minimum space requirement and wireless LFP data collection without externalised leads. This paper was to indicate a larger study which would formally recruit larger populations with PD and FOG. Future studies would explore FOG-related brain network coherence.


Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Realidade Virtual , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/etiologia , Marcha/fisiologia , Caminhada/fisiologia
12.
Nat Commun ; 14(1): 7723, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38001116

RESUMO

The rapid-developing soft robots and wearable devices require flexible conductive materials to maintain electric functions over a large range of deformations. Considerable efforts are made to develop stretchable conductive materials; little attention is paid to the frequent failures of integrated circuits caused by the interface mismatch of soft substrates and rigid silicon-based microelectronics. Here, we present a stretchable solder with good weldability that can strongly bond with electronic components, benefiting from the hierarchical assemblies of liquid metal particles, small-molecule modulators, and non-covalently crosslinked polymer matrix. Our self-solder shows high conductivity (>2×105 S m-1), extreme stretchability (~1000%, and >600% with chip-integrated), and high toughness (~20 MJ m-3). Additionally, the dynamic interactions within our solder's surface and interior enable a range of unique features, including ease of integration, component substitution, and circuit recyclability. With all these features, we demonstrated an application as thermoforming technology for three-dimensional (3D) conformable electronics, showing potential in reducing the complexity of microchip interfacing, as well as scalable fabrication of chip-integrated stretchable circuits and 3D electronics.

13.
Adv Mater ; : e2309821, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37993105

RESUMO

Bioinspired artificial skins integrated with reliable human-machine interfaces and stretchable electronic systems have attracted considerable attention. However, the current design faces difficulties in simultaneously achieving satisfactory skin-like mechanical compliance and self-powered multimodal sensing. Here, this work reports a microphase-separated bicontinuous ionogel which possesses skin-like mechanical properties and mimics the multimodal sensing ability of biological skin by ion-driven stimuli-electricity conversion. The ionogel exhibits excellent elasticity and ionic conductivity, high toughness, and ultrastretchability, as well as a Young's modulus similar to that of human skin. Leveraging the ion-polymer interactions enabled selective ion transport, the ionogel can output pulsing or continuous electrical signals in response to diverse stimuli such as strain, touch pressure, and temperature sensitively, demonstrating a unique self-powered multimodal sensing. Furthermore, the ionogel-based I-skin can concurrently sense different stimuli and decouple the variations of the stimuli from the voltage signals with the assistance of a machine-learning model. The ease of fabrication, wide tunability, self-powered multimodal sensing, and the excellent environmental tolerance of the ionogels demonstrate a new strategy in the development of next-generation soft smart mechano-transduction devices.

14.
Environ Res ; 238(Pt 2): 117186, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37741569

RESUMO

Currently, the storage of coal gasification slag (CGS) is continuously increasing, as the coal gasification technology develops, posing significant environmental hazards. Due to its volcanic ash characteristics and rich residual carbon, CGS has great potential for resource utilization, which has attracted the attentions of many scholars. This paper firstly introduces the compositions and properties of CGS. Then, it reviews the existing utilization methods of CGS, including Preparation of building materials, carbon-ash separation technology, ecological restoration, and cyclic blending. The advantages and disadvantages of various methods are compared. Subsequently, some high-value utilization methods of coal gasification slag are introduced, such as the preparation of high-performance activated carbon and zeolite, of which the feasibility and advantages are evaluated. Finally, some suggestions are put forward for future developing technologies. This paper aims to provide some references and inspiration for the utilization and environmental protection of CGS.


Assuntos
Carvão Mineral , Conservação dos Recursos Naturais , Carvão Vegetal , Cinza de Carvão
16.
Front Neurosci ; 17: 1163946, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37378015

RESUMO

Introduction: Hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) is a novel advanced non-invasive presurgical examination tool for patients with drug-resistant epilepsy (DRE). This study aims to evaluate the utility of PET/MRI in patients with DRE who undergo stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RFTC). Methods: This retrospective study included 27 patients with DRE who underwent hybrid PET/MRI and SEEG-guided RFTC. Surgery outcome was assessed using a modified Engel classification, 2 years after RFTC. Potential areas of the seizure onset zone (SOZ) were identified on PET/MRI and confirmed by SEEG. Results: Fifteen patients (55%) became seizure-free after SEEG-guided RFTC. Engel class II, III, and IV were achieved in six, two, and four patients, respectively at the 2 years follow-up. MRI was negative in 23 patients and structural abnormalities were found in four patients. Hybrid PET/MRI contributed to the identification of new structural or metabolic lesions in 22 patients. Concordant results between PET/MRI and SEEG were found in 19 patients in the identification of SOZ. Among the patients with multifocal onset, seizure-free status was achieved in 50% (6/12). Conclusion: SEEG-guided RFTC is an effective and safe treatment for drug-resistant epilepsy. Hybrid PET/MRI serves as a useful tool for detecting the potential SOZs in MRI-negative patients and guide the implantation of SEEG electrodes. Patients with multifocal epilepsy may also benefit from this palliative treatment.

17.
Seizure ; 107: 81-90, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36996757

RESUMO

BACKGROUND: Stereo-electroencephalography (SEEG) and magnetoencephalography (MEG) have generally been used independently as part of the pre-surgical evaluation of drug-resistant epilepsy (DRE) patients. However, the possibility of simultaneously employing these recording techniques to determine whether MEG has the potential of offering the same information as SEEG less invasively, or whether it could offer a greater spatial indication of the epileptogenic zone (EZ) to aid surgical planning, has not been previously evaluated. METHODS: Data from 24 paediatric and adult DRE patients, undergoing simultaneous SEEG and MEG as part of their pre-surgical evaluation, was analysed employing manual and automated high-frequency oscillations (HFOs) detection, and spectral and source localisation analyses. RESULTS: Twelve patients (50%) were included in the analysis (4 males; mean age=25.08 years) and showed interictal SEEG and MEG HFOs. HFOs detection was concordant between the two recording modalities, but SEEG displayed higher ability of differentiating between deep and superficial epileptogenic sources. Automated HFO detector in MEG recordings was validated against the manual MEG detection method. Spectral analysis revealed that SEEG and MEG detect distinct epileptic events. The EZ was well correlated with the simultaneously recorded data in 50% patients, while 25% patients displayed poor correlation or discordance. CONCLUSION: MEG recordings can detect HFOs, and simultaneous use of SEEG and MEG HFO identification facilitates EZ localisation during the presurgical planning stage for DRE patients. Further studies are necessary to validate these findings and support the translation of automated HFO detectors into routine clinical practice.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Adulto , Masculino , Humanos , Criança , Magnetoencefalografia/métodos , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia/métodos , Epilepsia/diagnóstico , Epilepsia/cirurgia , Emprego
18.
ACS Appl Mater Interfaces ; 15(8): 11379-11387, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36791211

RESUMO

On-skin electronic sensors are demanded for healthcare monitoring such as the continuous recording of biopotential and motion signals from patients. However, the mechanical mismatches and poor interface adhesion at the skin/sensor interfaces always cause high interfacial impedance and artifacts, frequent interfacial failure, and unexpected depletion of the device, which significantly limit the performance of the sensors. We here develop an on-skin sensor based on a conductive pressure-sensitive tape, which is assembled from supramolecular dual-cross-linked hydrogel composites. Both covalent and noncovalent cross-links in the hydrogel networks could harvest high flexibility, pressure-sensitive adhesion, and high interfacial toughness altogether, enabling a convenient "Press-N-Go" application of the sensor on human skin without additional pre/post-treatment on the skin or the senor. The high conformability and low resistivity of the tape can sustainably lower the interfacial impedance and thus improve signal quality in various measurement conditions. Our design provides a feasible path to develop interface-toughened on-skin electronics, which is desired in dynamic human-machine interfaces.


Assuntos
Dispositivos Eletrônicos Vestíveis , Humanos , Pele , Condutividade Elétrica , Impedância Elétrica , Hidrogéis
19.
J Gen Psychol ; 150(3): 267-277, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35285419

RESUMO

The influence of the self on memory processes has been extensively investigated (the self-reference effect) both explicitly (trait-rating paradigm) and implicitly (ownership paradigm). The groups that are closely related to the self are an important part of self-concept, and group-reference facilitated recall to the same extent as self-referencing using trait-rating paradigm. The current research employed an ownership procedure to investigate the impact of group ownership on memory using the participants' family served as the reference group. In both experiments, participants were asked to sort items into baskets that belonged to their family or a fictitious family. A subsequent recognition test showed that there was a significant memory advantage for objects that owned by their family, and the ownership effect was found in remember, but not know, responses. This finding suggests that transient ingroup-ownership of items had a significant memory dominance effect, and the enhancing effect of ownership leads to recollective experience.


Assuntos
Propriedade , Reconhecimento Psicológico , Humanos , Reconhecimento Psicológico/fisiologia , Memória , Rememoração Mental , Autoimagem
20.
Ann Neurol ; 93(2): 244-256, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36088542

RESUMO

OBJECTIVE: Despite the increasing number of genes associated with Charcot-Marie-Tooth (CMT) disease, many patients currently still lack appropriate genetic diagnosis for this disease. Autosomal dominant mutations in aminoacyl-tRNA synthetases (ARSs) have been implicated in CMT. Here, we describe causal missense mutations in the gene encoding seryl-tRNA synthetase 1 (SerRS) for 3 families affected with CMT. METHODS: Whole-exome sequencing was performed in 16 patients and 14 unaffected members of 3 unrelated families. The functional impact of the genetic variants identified was investigated using bioinformatic prediction tools and confirmed using cellular and biochemical assays. RESULTS: Combined linkage analysis for the 3 families revealed significant linkage (Zmax LOD = 6.9) between the genomic co-ordinates on chromosome 1: 108681600-110300504. Within the linkage region, heterozygous SerRS missense variants segregated with the clinical phenotype in the 3 families. The mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation. INTERPRETATION: Our findings suggest the heterozygous SerRS variants identified represent a novel cause for autosomal dominant CMT. Mutant SerRS proteins are known to impact various molecular and cellular functions. Our findings provide significant advances on the current understanding of the molecular mechanisms associated with ARS-related CMT. ANN NEUROL 2023;93:244-256.


Assuntos
Doença de Charcot-Marie-Tooth , Serina-tRNA Ligase , Humanos , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/metabolismo , Serina-tRNA Ligase/genética , Mutação , Heterozigoto , Mutação de Sentido Incorreto/genética
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