Characteristics of tandem repeat inheritance and sympathetic nerve involvement in GAA-FGF14 ataxia.

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.

Heterozygous Seryl-tRNA Synthetase 1 Variants Cause Charcot-Marie-Tooth Disease.

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.

Mechanism of NCNTs Growth on Foamed Nickel and Thus-Prepared PS Hydrogenation High-Performance Carrier NCNTs@FN.

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.

GGC Repeat Expansion of RILPL1 is Associated with Oculopharyngodistal Myopathy.

OBJECTIVE: Oculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ptosis, dysarthria, ophthalmoplegia, and distal muscle weakness. Recent studies revealed that GGC repeat expansions in 5'-UTR of LRP12, GIPC1, and NOTCH2NLC are associated with OPDM. Despite these advances, approximately 30% of OPDM patients remain genetically undiagnosed. Herein, we aim to investigate the genetic basis for undiagnosed OPDM patients in two unrelated Chinese Han families. METHODS: Parametric linkage analysis was performed. Long-read sequencing followed by repeat-primed polymerase chain reaction and amplicon length polymerase chain reaction were used to determine the genetic cause. Targeted methylation sequencing was implemented to detect epigenetic changes. The possible pathogenesis mechanism was investigated by quantitative polymerase chain reaction, immunoblotting, RNA fluorescence in situ hybridization, and immunofluorescence staining of muscle biopsy samples. RESULTS: The disease locus was mapped to 12q24.3. Subsequently, GGC repeat expansion in the promoter region of RILPL1 was identified in six OPDM patients from two families, findings consistent with a founder effect, designated as OPDM type 4. Targeted methylation sequencing revealed hypermethylation at the RILPL1 locus in unaffected individuals with ultralong expansion. Analysis of muscle samples showed no significant differences in RILPL1 mRNA or RILPL1 protein levels between patients and controls. Public CAGE-seq data indicated that alternative transcription start sites exist upstream of the RefSeq-annotated RILPL1 transcription start site. Strand-specific RNA-seq data revealed bidirectional transcription from the RILPL1 locus. Finally, fluorescence in situ hybridization/immunofluorescence staining showed that both sense and antisense transcripts formed RNA foci, and were co-localized with hnRNPA2B1 and p62 in the intranuclear inclusions of OPDM type 4 patients. INTERPRETATION: Our findings implicate abnormal GGC repeat expansions in the promoter region of RILPL1 as a novel genetic cause for OPDM, and suggest a methylation mechanism and a potential RNA toxicity mechanism are involved in OPDM type 4 pathogenesis. ANN NEUROL 2022;92:512-526.

Multifunctional small molecule for controlled assembly of oligomeric nanoparticles and crosslinked polymers.

One multifunctional small molecule can undergo a natural condensation reaction under the control of reducing agent to generate amphiphilic oligomers which quickly self-assemble supramolecular nanoparticles or form crosslinked, reversibly degradable polymers.

[Study on ultraviolet upconversion emissions of Gd3+ induced by Tm3+ under 980 nm excitation].

Series of Tm3+/Yb3+ co-doped GdF3 powders were synthesized through an easy and mild hydrothermal method. The phase and purity of powders were characterized by powder X-ray diffraction (XRD) (Rigaku RU-200b). The morphologies of the samples were characterized by field emission scanning electron microscopy (FE SEM) (Hitachi S-4800). The ultraviolet (UV) up-conversion (UC)emission spectra were recorded by a fluorescence spectrophotometer (Hitachi F-4500) with a 980 nm semiconductor continuous wave laser diode as the excitation source. And the luminescent dynamics was measured by excitation with 980 nm using an optical parameter oscillator (OPO) laser pumped by a pulsed Nd : YAG laser with a pulse duration of 10 ns, repetition frequency of 10 Hz, and the signal was recorded by using a monochromator and an oscillograph. Under 980 nm excitation, Gd3+, acting as a kind of host ion in the studied system, and its UV UC emissions were observed and studied. The luminescent dynamics of the characteristic emission of Gd3+ (311.6 nm, 6P7/2 --> 8S7/2) was explored and studied. The luminescent dynamics analysis results indicated that, on UV UC emissions of Gd3+, Yb3+ ions served as primary sensitizer ions successively transferring energy to Tm3+ to populate the 3P2 level. Then, Tm3+ ions served as secondary sensitizer ions transferring energy to populate the multiple 6 I(J) states of Gd3+ 3P2 --> 3H6 (Tm3+): 8S7/2 --> 6 I(J) (Gd3+). Further, 6D(J) levels were populated through other energy transfer processes between Gd3+ and Yb3+ or Tm3+. Finally, UV UC emissions from the excited 6D9/2, 6 I(J), 6P5/2, and 6P7/2 states to the ground state 8S7/2 were observed. Meanwhile, Tm3+ acted as activator in its own UC emissions, and the article did not put emphasis on those except the 3P2 and 1 I6 levels to the ground state 3 H6 transitions. Especially, the dependences of UV UC emissions of Gd3+ on the Yb3+ concentrations, the Tm3+ concentrations, the annealing temperatures, and the excitation power densities of the 980 nm semiconductor continuous wave laser diode were studied, too.

[A novel red phosphor (La3PO7:Eu3+) prepared by solid state method].

Novel red phosphor, Eu3+ -doped oxyphosphate (La3 PO7:Eu3+), was synthesized by a solid state method under high temperature. All the starting materials were analytical grade. La2O3, EuO3 and (NH4)2HPO4 weighed in appropriated molar ratios and ground in an agate mortar. Then the powder was treated under 1000 degrees C. The crystal phase of La3PO7:Eu3+ was investigated by X-ray diffraction (XRD) using a Cu target radiation resource (lamda = 1.54078 ?) and exhibited prominent peaks accordant with JCPDS standard card (33-0720) of La3PO7 in monoclinic phase. Emission and excitation spectra of La3PO7:Eu3+ were recorded at room temperature using a fluorescence spectrometer (Hitachi F-4500). Under 254 nm excitation, intense red fluorescence was observed from La3PO7:Eu3+, which was assigned to the (5)D0-->(7)F2 transition of Eu3+ ions. The intensity of the (5)D0-->(7)F2 transition is stronger than that of the (5)D0-->(7)F1 transition, showing that the Eu3+ ions were in the non-centrosym-metric sites in La3PO7. The CommissionIn-ternational DeL" Eclairage (CIE) coordinate of La3PO7:Eu3+ is (0.63,0.37) in the red area of CIE1931 XY chromaticity coordinate graph and close to that of Y2o3:Eu3+, but the cost of La3PO7 host is lower. This novel material may have potential applications in plasma display panels and Hg-free fluorescent lamps in the future.

Neural Correlation between Evoked Tactile Sensation and Central Activities in the Somatosensory Cortex.

Evoked tactile sensation (ETS) is induced with stimulation of areas in the projected finger map (PFM) in the stump skin of forearm amputees. The aim of the present study is to further explore the neural correlation of the ETS with central activities in the somatosensory cortex (SI). Two forearm amputees were recruited to participate in this study. The neuroimaging technique of Magnetoencephalography (MEG) was employed to reveal the activities in the somatosensory cortex (SI), while the thumb and little finger areas in the PFM and the thumb and little finger of the contralateral hand were stimulated with a bi-phasic current pulse train. In one subject, local anesthesia was applied to the skin areas of the thumb and little finger of the PFM to examine the effects of blocking peripheral nerve transmission on the central activities in SI. Results obtained in the two subjects indicated that stimulation of the thumb and little finger areas in the PFM of amputated side produced the similar neural activities in the somatosensory cortex as those of stimulating the thumb and little finger of the contralateral hand, both of which were consistent with the homunculus organization of the SI cortex. The intensity of SI cortical activities was proportional to the intensity of the amplitude of peripheral stimulation. In particular, local anesthesia reduced the intensity of central activities in SI as revealed by the MEG response, as well as the sensitivity of ETS as reported by the subject. This neural correlation appears to suggest that the finger areas in the PFM in the stump skin are neuroanatomically connected to the finger areas of the somatosensory cortex. Thus, electrical stimulation of the PFM can induce natural sensation as that of normal fingers. This establishes the neural basis of natural sensory feedback from the prosthetic hand to the forearm amputee with finger-to-finger specificity.

Thermal activation of serpentine for adsorption of cadmium.

Thermal activated serpentine with high adsorption capacity for heavy metals was prepared. The batch experiment studies were conducted to evaluate the adsorption performance of Cd2+ in aqueous solution using thermal activated serpentine as adsorbent. These samples before and after adsorption were characterized by XRD, FT-IR, SEM, XPS, and N2 adsorption-desorption at low temperature. It was found that serpentine with layered structure transformed to forsterite with amorphous structure after thermal treatment at over 700°C, while the surface area of the samples was increased with activated temperature and the serpentine activated at 700°C (S-700) presented the largest surface area. The pH of solution after adsorption was increased in different degrees due to hydrolysis of MgO in serpentine, resulting in enhancing adsorption of Cd2+. The S-700 exhibited the maximum equilibrium adsorption capacity (15.21mg/g), which was 2 times more than pristine serpentine. Langmuir isotherm was proved to describe the equilibrium adsorption data better than Freundlich isotherm and pseudo second order kinetics model could fit the adsorption kinetics processes well. Based on the results of characterization with XPS and XRD, the adsorption mechanisms could be explained as primarily formation of CdCO3 and Cd(OH)2 precipitation on the surface of serpentine.

Modulations on cortical oscillations by subthalamic deep brain stimulation in patients with Parkinson disease: A MEG study.

OBJECTIVE: The study aimed to explore the modification to cortical oscillations of Parkinson disease (PD) patients by subthalamic nucleus deep brain stimulation (STN DBS). METHODS: With Magnetoencephalogram (MEG) detection, we examined the changes in absolute power spectrum of cortical oscillations in the PD patients with the treatment of STN DBS. RESULTS: The power analysis of PD patients showed a dominant over-synchronization of alpha and beta bands in temporal and occipital areas relative to the healthy control subjects. STN DBS on-state showed marked power increase in the gamma band of PD patients in the frontal and parietal relative to the DBS off-state. The alleviation of motor symptoms by STN DBS negatively correlated to the increase of high gamma oscillation in the right frontal cortex, and also correlated to the suppression of the alpha and beta oscillations in the right temporal cortex. CONCLUSION: The treatment of STN DBS to PD patients might involve the augmentation of gamma activity and suppression of alpha and beta activities in cortical oscillations.

In situ plasmonic Ag nanoparticle anchored TiO2 nanotube arrays as visible-light-driven photocatalysts for enhanced water splitting.

An ultrasonication-assisted in situ deposition strategy was utilised to uniformly decorate plasmonic Ag nanoparticles on vertically aligned TiO2 nanotube arrays (NTAs) to construct a Ag@TiO2 NTA composite. The Ag nanoparticles act as efficient surface plasmon resonance (SPR) photosensitizers to drive photocatalytic water splitting under visible light irradiation. The Ag nanoparticles were uniformly deposited on the surface and inside the highly oriented TiO2 nanotubes. The visible-light-driven hydrogen production activities of silver nanoparticle anchored TiO2 nanotube array photocatalysts were evaluated using methanol as a sacrificial reagent in water under a 500 W Xe lamp with a UV light cutoff filter (λ ≥ 420 nm). It was found that the hydrogen production rate of the Ag@TiO2 NTAs prepared with ultrasonication-assisted deposition for 5 min was approximately 15 times higher than that of its pristine TiO2 NTAs counterpart. The highly efficient photocatalytic hydrogen evolution is attributed to the SPR effect of Ag for enhanced visible light absorption and boosting the photogenerated electron-hole separation/transfer. This strategy is promising for the design and construction of high efficiency TiO2 based photocatalysts for solar energy conversion.

Ubiquitin-protein ligase E3C promotes glioma progression by mediating the ubiquitination and degrading of Annexin A7.

The ubiquitin-protein ligase E3C (UBE3C) belongs to the E3 ligase enzyme family and implicates in the ubiquitin-proteasome pathway, thus regulates physiological and cancer-related processes. Here, we investigated the expression and roles of UBE3C in glioma. We demonstrated that UBE3C was overexpressed in glioma tissues and cell lines. Inhibition of UBE3C expression in glioma cells significantly decreased cell migration and invasion in vitro. Mechanistically, we disclosed that UBE3C physically interacted with and ubiquitinated tumor suppressor gene annexin A7 (ANXA7), resulting in ubiquitination and degradation of ANXA7. Our results also revealed that increased UBE3C expression was accompanied by a reduction in ANXA7 protein expression in glioma tissues, but not ANXA7 mRNA. Importantly, the inhibition of ANXA7 expression in gliomas cells with UBE3C interference could rescue the cell invasion. Clinically, UBE3C overexpression significantly correlated with high-grade tumors (p < 0.05), poor overall survival, and early tumor recurrence. Thus, our data reveal that high UBE3C expression contributes to glioma progression by ubiquitination and degradation of ANXA7, and thus presents a novel and promising target for glioma therapy.

Controlled intracellular self-assembly of gadolinium nanoparticles as smart molecular MR contrast agents.

Herein we developed a new "smart" Gd-based MR contrast agent (i.e., 1) which is susceptive to furin, a protease overexpressed in tumor. Under the action of furin, 1 condenses to form dimers (1-Ds) and the latter self-assemble into gadolinium nanparticles (Gd-NPs). Relaxivity of 1-D is more than 2 folds of those of 1 and magnevist at 1.5 T, and 1.4 folds of that of 1 at 3 T. Intracellular condensation of 1 in furin-overexpressed MDA-MB-468 cells was proven with direct two-photon laser microscopy (TPLM) fluorescence imaging of the cells incubated with the europium analog of 1 (i.e., 2). Intracellular Gd-NPs of 1 were uncovered and characterized for the first time. MRI of MDA-MB-468 tumors showed that 1 has enhanced MR contrast within the tumors than that of its scrambled control 1-Scr.

Caspase-3 controlled assembly of nanoparticles for fluorescence turn on.

A caspase-3 controlled condensation was applied to self-assemble biotinylated nanoparticles for capturing FITC-labelled streptavidin and subsequently turning on the fluorescence signal.