Diverse CMT2 neuropathies are linked to aberrant G3BP interactions in stress granules.

Complex diseases often involve the interplay between genetic and environmental factors. Charcot-Marie-Tooth type 2 neuropathies (CMT2) are a group of genetically heterogeneous disorders, in which similar peripheral neuropathology is inexplicably caused by various mutated genes. Their possible molecular links remain elusive. Here, we found that upon environmental stress, many CMT2-causing mutant proteins adopt similar properties by entering stress granules (SGs), where they aberrantly interact with G3BP and integrate into SG pathways. For example, glycyl-tRNA synthetase (GlyRS) is translocated from the cytoplasm into SGs upon stress, where the mutant GlyRS perturbs the G3BP-centric SG network by aberrantly binding to G3BP. This disrupts SG-mediated stress responses, leading to increased stress vulnerability in motoneurons. Disrupting this aberrant interaction rescues SG abnormalities and alleviates motor deficits in CMT2D mice. These findings reveal a stress-dependent molecular link across diverse CMT2 mutants and provide a conceptual framework for understanding genetic heterogeneity in light of environmental stress.

Effects of High-Voltage Pulsed Radiofrequency on the Ultrastructure and Nav1.7 Level of the Dorsal Root Ganglion in Rats With Spared Nerve Injury.

OBJECTIVES: To investigate the analgesic effect of high-voltage pulsed radiofrequency (HV-PRF) on the dorsal root ganglion (DRG) for neuropathic pain induced by spared nerve injury (SNI) in rats, especially the influence of this treatment on the DRG ultrastructure and voltage-gated sodium channel 1.7 (Nav1.7) level in the DRG. MATERIALS AND METHODS: One hundred fifty adult male Sprague-Dawley rats were randomly divided into five groups: Sham, SNI, Free-PRF, standard-voltage PRF (SV-PRF), and HV-PRF. The 45V-PRF and 85V-PRF procedures applied to the left L5 DRG were performed in SV-PRF group and the HV-PRF group, respectively, on day 7 after SNI, whereas no PRF was concurrently delivered in Free-PRF group. The paw mechanical withdrawal threshold (PMWT) was detected before SNI (baseline) and on days 1, 3, 7, 8, 10, 14, and 21. The changes of left L5 DRG ultrastructure were analyzed with transmission electron microscopy on days 14 and 21. The expression levels of Nav1.7 in left L5 DRG were detected by immunofluorescence and Western blot. RESULTS: Compared with the Free-PRF group, PMWT in the SV-PRF group and HV-PRF group were both significantly increased after PRF (all p < 0.05). Meanwhile, the PMWT was significantly higher in the HV-PRF group than that in the SV-PRF group on days 14 and 21 (all p < 0.05). There were statistically significant differences between the SV-PRF and Free-PRF groups (p < 0.05). Similarly, statistically significant difference was found between the HV-PRF and Free-PRF groups (p < 0.05). Especially, comparison of the SV-PRF group and the HV-PRF group revealed statistically significant difference (p < 0.05). The Nav1.7 levels were significantly downregulated in the SV-PRF group and HV-PRF groups compared to that in the Free-PRF group (all p < 0.01). A significantly lower Nav1.7 level was also found in the HV-PRF group compared to that in the SV-PRF group (p < 0.05). CONCLUSIONS: The HV-PRF produces a better analgesic effect than SV-PRF applied to the DRG in SNI rats. The underlying mechanisms may be associated with improving the histopathological prognosis and the downregulation of Nav1.7 levels in the DRG.

Optical-aberrations-corrected light field re-projection for high-quality plenoptic imaging.

The singlet plenoptic camera, which consists of a single lens, microlens array (MLA) and image sensor, possesses the superiority that the imaging system is compact and lightweight, which is beneficial to miniaturization. However, such plenoptic cameras suffer from severe optical aberrations and their imaging quality is inferior for post-capture processing. Therefore, this paper proposes an optical-aberrations-corrected light field re-projection method to obtain high-quality singlet plenoptic imaging. First, optical aberrations are modeled by Seidel polynomials and included into point spread function (PSF) modeling. The modeled PSF is subsequently used to reconstruct imaging object information. Finally, the reconstructed imaging object information is re-projected back to the plenoptic imaging plane to obtain high-quality plenoptic images without optical aberrations. PSF modeling is validated by a self-built singlet plenoptic camera and the utility of the proposed optical-aberrations-corrected light field re-projection method is verified by numerical simulations and real imaging experiments.

A Series of Novel HDAC Inhibitors with Anthraquinone as a Cap Group.

Although anthraquinone derivatives possess significant antitumor activity, most of them also displayed those side effects like cardiotoxicity, mainly owing to their inhibition of topoisomerase II of DNA repair mechanisms. Our raised design strategy by switching therapeutic target from topoisomerase II to histone deacetylase (HDAC) has been applied to the design of anthraquinone derivatives in current study. Consequently, a series of novel HDAC inhibitors with a tricylic diketone of anthraquinone as a cap group have been synthesized. After screening and evaluation, compounds 4b, 4d, 7b and 7d have displayed the comparable inhibition in enzymatic activity and cell proliferation than that of Vorinostat (SAHA). Notably, compound 4b showed certain selectivity of antiproliferative effects on cancer cell lines over non-cancer cell lines.

A Three-Dimensional Finite Element Analysis Model for SH-SAW Torque Sensors.

In this paper, a three-dimensional finite element analysis (3D-FEA) model for shear horizontal surface acoustic wave (SH-SAW) torque sensors is presented. Torque sensors play a significant role in various fields to ensure a reliable torque transmission in drivelines. Featured with the advantages of high propagation velocity, large Q-value, and good power capacity, SH-SAW based torque sensors are promising but very few studies have been carried out. In order to develop a successful sensor, understanding the characteristics of SH-SAWs produced on piezoelectric substrates and torque sensing modes is indispensable. Therefore, in this study, we first investigated the effect on the generation of waves when different Y-cut quartz substrates are engaged. Thereafter, analyses and comparisons, regarding the effect on the polarized displacement, wave guidance, and wave mode, were conducted for different configurations of wave-guide layer thickness to wavelength ratios (hlayer/λ) and materials. Results show that Y-cut quartz at an angle close to 36° with a gold (Au) layer varying from hAu/λ = 0.02 to 0.03 thickness could be the most effective configuration for the excitation of SH-SAWs, compared to other combinations using platinum (Pt), titanium (Ti) and silicon dioxide (SiO2). Finally, based on the FEA SH-SAW torque sensor model configuring with a Y + 36° quartz substrate and 0.025 λ-thick gold layer, the relationship between the applied torque and sensed voltage was examined, which shows a perfect linearity demonstrating the performance of the sensors.

Distance measurement based on light field geometry and ray tracing.

In this paper, we propose a geometric optical model to measure the distances of object planes in a light field image. The proposed geometric optical model is composed of two sub-models based on ray tracing: object space model and image space model. The two theoretic sub-models are derived on account of on-axis point light sources. In object space model, light rays propagate into the main lens and refract inside it following the refraction theorem. In image space model, light rays exit from emission positions on the main lens and subsequently impinge on the image sensor with different imaging diameters. The relationships between imaging diameters of objects and their corresponding emission positions on the main lens are investigated through utilizing refocusing and similar triangle principle. By combining the two sub-models together and tracing light rays back to the object space, the relationships between objects' imaging diameters and corresponding distances of object planes are figured out. The performance of the proposed geometric optical model is compared with existing approaches using different configurations of hand-held plenoptic 1.0 cameras and real experiments are conducted using a preliminary imaging system. Results demonstrate that the proposed model can outperform existing approaches in terms of accuracy and exhibits good performance at general imaging range.

Point spread function and depth-invariant focal sweep point spread function for plenoptic camera 2.0.

This paper derives a mathematical point spread function (PSF) and a depth-invariant focal sweep point spread function (FSPSF) for plenoptic camera 2.0. Derivation of PSF is based on the Fresnel diffraction equation and image formation analysis of a self-built imaging system which is divided into two sub-systems to reflect the relay imaging properties of plenoptic camera 2.0. The variations in PSF, which are caused by changes of object's depth and sensor position variation, are analyzed. A mathematical model of FSPSF is further derived, which is verified to be depth-invariant. Experiments on the real imaging systems demonstrate the consistency between the proposed PSF and the actual imaging results.

A high-performance nanobridged MoO3 UV photodetector based on nanojunctions with switching characteristics.

Ultraviolet photodetectors (UVPDs) were fabricated via the in situ growth of orthorhombic MoO3 nanobelts among interdigital electrodes. Two types of nanojunction, touching and interpenetration, were formed between neighboring nanobelts at different growth conditions. The photoresponse mechanism of the UVPDs greatly depends on the type of nanojunction. Nanojunctions formed with touching nanobelts possess switching characteristics due to the barrier height variation along with the UV illumination. The UVPD with the touching structure exhibits low noise, high UV sensitivity and fast speed, having a dark current of 1.4 nA, an on/off ratio of over 100 and a response time of below 1 s, at an applied voltage of 10 V. The enhanced performance can be attributed to the switching characteristics of the touching nanojunction.

Birth of a Mosaic Non­Down Syndrome Offspring to a 45,XY,t(21;21)(q10;q10) Homologous Robertsonian Translocation Carrier: A Case Report.

BACKGROUND: Homologous Robertsonian translocation carriers have been considered to have no chance, theoretically, of having a normal embryo. For these carriers, traditional genetic counseling would suggest using donated sperm or oocyte rather than using their own gametes. CASE: This study reports the case of a 45,XY,t(21;21)(q10;q10) homologous Robertsonian translocation carrier who had an approximately normal offspring with a mosaic karyotype: 46,XX,[86]/46, XX,t(21;21)[14]. CONCLUSION: Carriers of homologous Robertsonian translocations might have a chance of having normal offspring. For these carriers, besides traditional assisted reproductive technology such as using gametes from a donor, preimplantation genetic diagnosis might have clinical value.

Serum levels of interleukin-1 beta, interleukin-6 and melatonin over summer and winter in kidney deficiency syndrome in Bizheng rats.

OBJECTIVE: To observe the seasonal changes in serum levels of interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and melatonin (MT) in Bizheng rat model, and explore the relationship between MT and the pathogenesis of rheumatoid arthritis. METHODS: One hundred and sixty Sprague-Dawley rats were randomly divided into four groups in summer (n=80) and winter (n=80) respectively: normal group, collagen-induced arthritis (CIA) model group, operation group, and sham-operation group (n=20 in each group). The CIA model group was injected with collagen emulsion at the base of the tail to induce arthritis. The rats in the operation group received pineal gland resection, and 7 days after the first operation, underwent testectomy or oophorectomy. The rats in the sham-operation group were operated to ligature the sagittal sinus, without extracting the pineal gland. After the operations, the operation group and the sham-operation group both were immunized as the CIA group was. The serum levels of IL-1ß, IL-6 and MT in different groups were measured by radioimmunoassay. RESULTS: Compared with the normal group, the serum levels of IL-1ß and IL-6 increased in the CIA model, operation, and sham-operation groups both in summer and in winter (IL-1ß in summer, P=0.008, P<0.01, P=0.012; IL-1ß in winter, P=0.019, P<0.01, P=0.027; IL-6 in summer, P=0.028, P<0.01, P=0.024; IL-6 in winter, P=0.006, P<0.01, P=0.008). In the operation group, the serum levels of IL-1ß and IL-6 in winter were higher than in summer, but with no statistically significant differences (P=0.844, 0.679). Compared with the normal group, the serum level of MT significantly increased in summer and winter in both the CIA model group (P=0.002, 0.008) and the sham-operation group (P=0.003, 0.007), while significantly decreased in the operation group (P=0.023, 0.003). There was no significant difference in MT level in the operation group between summer and winter (P=0.947). CONCLUSIONS: The increase of serum levels of IL-1ß and IL-6 may exacerbate the inflammatory reaction and cause a more severe condition in the rheumatoid arthritis. The concentrations of IL-1ß, IL-6, and MT correspond with the change of seasons, confirming that there are connections between nature and human body.

High-voltage pulsed radiofrequency improves ultrastructure of DRG and enhances spinal microglial autophagy to ameliorate neuropathic pain induced by SNI.

Neuropathic pain (NeP) is intractable for which many therapies are ineffective. High-voltage pulsed radiofrequency (HVPRF) on dorsal root ganglion (DRG) is considered an effective treatment for NeP. The aim of this study is to explore the therapeutic voltage for the optimal efficacy of PRF and the underlying mechanisms. The radiofrequency electrode was placed close to the L5 DRG of rats with spared nerve injury (SNI) and emitted current by the corresponding voltage in different groups. Four different voltages (45 V, 65 V, 85 V, and 100 V) of PRF on DRG significantly alleviated the SNI-induced NeP, reduced the levels of activating transcription factor 3 (ATF3) in DRG, improved the ultrastructure of DRG, and promoted autophagy in spinal microglia to varying degrees and partially reversed the increased expression of TNF-α and the reduced expression of IL-10 in spinal cord dorsal horn (SCDH). The beneficial effect of 85V-PRF was superior to those of other three PRF treatments. The underlying mechanisms may be related to repairing the DRG damage and improving the DRG ultrastructure while regulating spinal microglial autophagy and thereby alleviating neuroinflammation.

The role of Immune cells in Alzheimer's disease: a bidirectional Mendelian randomization study.

Background: Alzheimer's disease (AD) is a leading cause of dementia, characterized by the accumulation of amyloid-beta (Aß) and hyperphosphorylated tau proteins, leading to neuroinflammation and neuronal damage. The role of the immune system in AD pathogenesis is increasingly recognized, prompting an exploration of the causal relationship between immune cells and AD by using Mendelian randomization (MR) approaches. Methods: Utilizing genome-wide association study (GWAS) data from European cohorts, we conducted an MR study to investigate the causal links between immune cell phenotypes and AD. We selected single nucleotide polymorphisms (SNPs) associated with immune cell traits at a genome-wide significance threshold and applied various MR methods, including MR Egger, Weighted median, and inverse variance weighted analysis, to assess the causality between 731 immune phenotypes and AD. Results: Our MR analysis identified 15 immune cell types with significant causal relationships to AD pathogenesis. Notably, the absolute count of CD28-CD4-CD8- T cells and the expression of HLA DR on B cells were linked to a protective effect against AD, while 13 other immune phenotypes were identified as contributing to the risk factors for the disease. The causal effects of AD on immunophenotypic traits are predominantly negative, implying that AD may impair the functionality of immune cells. Validation through independent datasets, such as FinnGen and GCST90027158, confirmed the causal association between six specific immune cells and AD. Conclusion: This comprehensive MR study elucidates the intricate network of causal relationships between diverse immunophenotypic traits and AD, providing novel insights into the immunopathogenesis of AD. The findings suggest potential immunological targets that could be leveraged for early diagnosis, disease monitoring, and therapeutic intervention.

The potential therapeutic roles of dental pulp stem cells in spinal cord injury.

Spinal cord injury (SCI) can lead to serious functional disorders, which have serious impacts on patients and society. The current traditional treatments of SCI are not effective the injured spinal cord is difficult to repair and regenerate. In recent years, stem cell transplantation for the treatment of SCI has been a hot research topic. Dental pulp stem cells have strong abilities of self-renewal and multi-directional differentiation, and have been applied for tissue engineering and regenerative medicine. And dental pulp stem cells have certain advantages in neuro-regenetation, bringing new hope to biotherapy for SCI. This article reviews the characteristics of dental pulp stem cells and their research progress in the treatment of SCI.

The controlling nutritional status score and risk factors associated with malnutrition in patients with acute ischemic stroke.

Objectives: Malnutrition is an independent risk factor for poor outcomes in patients who suffered an acute ischemic stroke (AIS). The controlling nutritional status (CONUT) score can provide information for nutritional management in AIS patients. However, the risk factors associated with the CONUT score have not been established to date. Therefore, in this study, we aimed to investigate the CONUT score of patients with AIS and explore the potential risk factors associated with it. Methods: We conducted a retrospective review of the data from consecutive AIS patients who were recruited in the CIRCLE study. Within 2 days of admission, we gathered the CONUT score, the Nutritional Risk Screening 2002, the Modified Rankin Scale, the National Institutes of Health Neurological Deficit Score (NIHSS), and demographic data from medical records. We used chi-squared tests to examine admission, and a logistic regression analysis was performed to explore the risk factors associated with CONUT in patients with AIS. Results: A total of 231 patients with AIS participated in the study, with a mean age of 62.32 ± 13.0 years and a mean NIHSS of 6.77 ± 3.8. Of these patients, 41(17.7%) had hyperlipidemia. In terms of nutritional assessment, 137(59.3%) patients with AIS had high CONUT scores, 86(37.2%) patients with AIS had low or high BMI, and 117(50.6%) patients with AIS had NRS-2002 scores below 3. The chi-squared tests showed that age, NIHSS, body mass index (BMI), and hyperlipidemia were associated with the CONUT score (P < 0.05). The logistic regression analysis showed that low NIHSS scores (OR = 0.055 95% CI: 0.003-0.893), younger age (OR = 0.159 95% CI: 0.054-0.469), and hyperlipidemia (OR = 0.303 95% CI: 0.141-0.648) were independently associated with lower CONUT scores (P < 0.05), whereas BMI was not found to be independently associated with the CONUT. Conclusions: More than half of the patients with AIS were at risk of malnutrition, with age and neurological deficits being identified as risk factors for nutritional control. Hyperlipidemia was found to be a protective factor of the CONUT, while NRS-2002 and BMI did not affect the nutritional control in patients with AIS.

Creation of four-mode weighted cluster states with atomic ensembles in high-Q ring cavities.

Two schemes for the preparation of weighted continuous variable cluster states with four atomic ensembles are proposed. In the first scheme, the four separated atomic ensembles inside a two-mode ring cavity are driven by pulse laser fields. The basic idea of the scheme is to transfer the ensemble bosonic modes into suitable linear combinations that can be prepared in a pure cluster state by a sequential application of the laser pulses with the aid of the cavity dissipation. In the second one, we take two separate two-mode cavities, each containing two atomic ensembles. The distant cavities are coupled by dissipation in a cascade way. It has been found that the mixed cluster state can be produced. These schemes may contribute towards implementing continuous variable quantum computation, quantum communication and networking based on atomic ensembles.

In vitro evaluation of schistosomicidal potential of curcumin against Schistosoma japonicum.

Curcumin is a polyphenol derived from the dietary spice turmeric. The aim of this study was to investigate the in vitro effect of curcumin against eggs, cercariae, pre-adults, and adults of Schistosoma japonicum compared to praziquantel. After incubated by different concentration of curcumin or praziquantel in different time, the percent hatching rates of eggs, the percent dead rates of cercariae, and the number of dead worms were observed. Curcumin showed time- and dose-dependent schistosomicidal effects on every life stages of S. japonicum. In addition, curcumin exhibited an optimal activity against the adult stage with no differential sensitivity between male and female worms and decreased motor activity of these worms without tegumental alterations. The promising in vitro effects on all stages of S. japonicum warrants further evaluation for the prophylactic and therapeutic values in the early and late schistosomiasis in field trials.

Limb heaviness as a sensorimotor disorder alters rehabilitation adherence after a stroke.

Introduction: To the best of our knowledge, it is still unknown how perceived limb heaviness affects rehabilitation adherence. As rehabilitation adherence is very important for the functional recovery of patients with stroke, it is important to explore the relationship between perceived limb heaviness and rehabilitation adherence. Methods: We retrospectively reviewed the data of patients with consecutive stroke recruited in the CIRCLE study. The influence of age, gender, time from onset to enrollment, educational background, hypertension, diabetes, Modified Rankin Scale (MRS), and National Institutes of Health Stroke Scale (NIHSS) on rehabilitation adherence was analyzed. Multiple linear regression analysis was used to examine the association between perceived limb heaviness and rehabilitation adherence changes. Results: A total of 108 participants completed the study. About 40 (37.0%) participants felt limb heaviness. The mean scores on the Medical Research Council (MRC) scale for the upper affected limb strength were 3.05 ± 1.7, and the mean score on the exercise adherence questionnaire (EAQ) was 34.27 ± 8.9. Univariate analysis showed that rehabilitation adherence levels differed in upper limb muscle strength and whether they perceived limb heaviness. After adjustment for independent predictors, we found that perceived limb heaviness was associated with rehabilitation adherence (B = -9.681 ± 1.494, p < 0.05) and R 2 was 0.332 and 0.074 if the muscle strength of the upper limb and perceived limb heaviness were included in the model and the model was without perceived limb heaviness, respectively. Conclusion: By identifying patients with stroke with limb heaviness, it led to lower levels of motor functional rehabilitation adherence. We must pay more attention to limb heaviness and provide effective interventions to improve rehabilitation adherence and promote patient recovery.

Effect of Clamping Compression on the Mechanical Performance of a Carbon Paper Gas Diffusion Layer in Polymer Electrolyte Membrane Fuel Cells.

During all the assembly stages of a polymer electrolyte membrane fuel cell (PEMFC) stack, gas diffusion layers (GDLs) endure clamping loads in the through-plane direction several times. Under such complicated assembly conditions, GDLs have to deform with the changes in structure, surface roughness, pore size, etc. A comprehensive understanding of the compressive performance of GDLs at different clamping phases is crucial to the assembly process improvement of PEMFCs. Two typical clamping compression was designed and performed to get close to the actual assembly conditions of PEMFCs. The results indicate that the initial clamping compression and the magnitude of the maximum clamping load have great impacts on the segmented compressive properties of GDLs. The nonlinear compressive performance of the GDL is mainly attributed to the unique microstructural information. The rough surface morphology contributes to the initial compressive characteristics where the big strain along with the small stress occurs, and the irreversible failures such as carbon fiber breakages and adhesive failures between fibers and binders account for the hysteresis between different compression stages. Importantly, it is found that the clamping compression hardly influences the small pore distribution below 175 µm but affects the large pore distribution over 200 µm.

The Effect of Preoperative Rehabilitation Training on the Early Recovery of Joint Function after Artificial Total Knee Arthroplasty and Its Effect Evaluation.

OBJECTIVE: To study the effect of preoperative rehabilitation training on the rehabilitation of patients after total knee arthroplasty. METHODS: A total of 120 patients diagnosed with knee osteoarthritis and undergoing total knee arthroplasty were selected and divided into experimental group and control group according to a random number table, with 60 cases in each group. The control group only carried out routine clinical nursing before the operation, and the experimental group used the formulated preoperative rehabilitation training method based on the control group for training. By comparing the visual analogue score (VAS), keen society score (KSS), postoperative time to get out of bed for the first time, patient satisfaction, and other related indicators between the two groups of patients, the recovery of keen joint function of patients after surgery was evaluated. RESULTS: The visual analogue scale (VAS) of the experimental group was significantly lower than that of the experimental group at three days after operation. The keen society score (KSS) of the experimental group was significantly better than that of the control group at three days after surgery and one month after surgery. The time to get out of bed for the first time after operation in the experimental group (44.93 ± 13.63) was significantly less than that in the control group (78.33 ± 13.52). The patient satisfaction of the experimental group was significantly higher than that of the control group (88.30 ± 3.61). The above statistical results were all p < 0.05 of the two groups, and the differences were statistically significant. CONCLUSION: Preoperative rehabilitation training can significantly reduce the pain of patients after knee replacement, improve the functional state of knee joints, shorten the time to get out of bed for the first time after surgery, and win the best recovery opportunity, which can better improve patient satisfaction in hospitalization and improve medical care services level.

Solution-Processed CsPbBr3 Quantum Dots/Organic Semiconductor Planar Heterojunctions for High-Performance Photodetectors.

Planar heterojunctions (PHJs) are fundamental building blocks for construction of semiconductor devices. However, fabricating PHJs with solution-processable semiconductors such as organic semiconductors (OSCs) is a challenge. Herein, utilizing the orthogonal solubility and good wettability between CsPbBr3 perovskite quantum dots (PQDs) and OSCs, fabrication of solution-processed PQD/OSC PHJs are reported. The phototransistors based on bilayer PQD/PDVT-10 PHJs show responsivity up to 1.64 × 104 A W-1 , specific detectivity of 3.17 × 1012 Jones, and photosensitivity of 5.33 × 106 when illuminated by 450 nm light. Such high photodetection performance is attributed to efficient charge dissociation and transport, as well as the photogating effect in the PHJs. Furthermore, the tri-layer PDVT-10/PQD/Y6 PHJs are used to construct photodiodes working in self-powered mode, which exhibit broad range photoresponse from ultraviolet to near-infrared, with responsivity approaching 10-1 A W-1 and detectivity over 106 Jones. These results present a convenient and scalable production processes for solution-processed PHJs and show their great potential for optoelectronic applications.