QTL mapping for plant height and ear height using bi-parental immortalized heterozygous populations in maize.

Introduction: Plant height (PH) and ear height (EH) are key plant architectural traits in maize, which will affect the photosynthetic efficiency, high plant density tolerance, suitability for mechanical harvesting. Methods: QTL mapping were conducted for PH and EH using a recombinant inbred line (RIL) population and two corresponding immortalized backcross (IB) populations obtained from crosses between the RIL population and the two parental lines. Results: A total of 17 and 15 QTL were detected in the RIL and IB populations, respectively. Two QTL, qPH1-1 (qEH1-1) and qPH1-2 (qEH1-4) in the RIL, were simultaneously identified for PH and EH. Combing reported genome-wide association and cloned PH-related genes, co-expression network analyses were constructed, then five candidate genes with high confidence in major QTL were identified including Zm00001d011117 and Zm00001d011108, whose homologs have been confirmed to play a role in determining PH in maize and soybean. Discussion: QTL mapping used a immortalized backcross population is a new strategy. These identified genes in this study can provide new insights for improving the plant architecture in maize.

A conserved ion channel function of STING mediates noncanonical autophagy and cell death.

The cGAS/STING pathway triggers inflammation upon diverse cellular stresses such as infection, cellular damage, aging, and diseases. STING also triggers noncanonical autophagy, involving LC3 lipidation on STING vesicles through the V-ATPase-ATG16L1 axis, as well as induces cell death. Although the proton pump V-ATPase senses organelle deacidification in other contexts, it is unclear how STING activates V-ATPase for noncanonical autophagy. Here we report a conserved channel function of STING in proton efflux and vesicle deacidification. STING activation induces an electron-sparse pore in its transmembrane domain, which mediates proton flux in vitro and the deacidification of post-Golgi STING vesicles in cells. A chemical ligand of STING, C53, which binds to and blocks its channel, strongly inhibits STING-mediated proton flux in vitro. C53 fully blocks STING trafficking from the ER to the Golgi, but adding C53 after STING arrives at the Golgi allows for selective inhibition of STING-dependent vesicle deacidification, LC3 lipidation, and cell death, without affecting trafficking. The discovery of STING as a channel opens new opportunities for selective targeting of canonical and noncanonical STING functions.

Genetic architecture of ear traits based on association mapping and co-expression networks in maize inbred lines and hybrids.

Ear traits are key contributors to grain yield in maize; therefore, exploring their genetic basis facilitates the improvement of grain yield. However, the underlying molecular mechanisms of ear traits remain obscure in both inbred lines and hybrids. Here, two association panels, respectively, comprising 203 inbred lines (IP) and 246 F1 hybrids (HP) were employed to identify candidate genes for six ear traits. The IP showed higher phenotypic variation and lower phenotypic mean than the HP for all traits, except ear tip-barrenness length. By conducting a genome-wide association study (GWAS) across multiple environments, 101 and 228 significant single-nucleotide polymorphisms (SNPs) associated with six ear traits were identified in the IP and HP, respectively. Of these significant SNPs identified in the HP, most showed complete-incomplete dominance and over-dominance effects for each ear trait. Combining a gene co-expression network with GWAS results, 186 and 440 candidate genes were predicted in the IP and HP, respectively, including known ear development genes ids1 and sid1. Of these, nine candidate genes were detected in both populations and expressed in maize ear and spikelet tissues. Furthermore, two key shared genes (GRMZM2G143330 and GRMZM2G171139) in both populations were found to be significantly associated with ear traits in the maize Goodman diversity panel with high-density variations. These findings advance our knowledge of the genetic architecture of ear traits between inbred lines and hybrids and provide a valuable resource for the genetic improvement of ear traits in maize. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01426-9.

Characterization of the Isocitrate Dehydrogenase Gene Family and Their Response to Drought Stress in Maize.

Isocitrate dehydrogenase (IDH) is a key rate-limiting enzyme in the tricarboxylic acid cycle and acts in glutamine synthesis. IDH also participates in plant growth and development and in response to abiotic stresses. We identified 11 maize IDH genes (ZmIDH) and classified these genes into ZmNAD-IDH and ZmNADP-IDH groups based on their different coenzymes (NAD+ or NADP+). The ZmNAD-IDH group was further divided into two subgroups according to their catalytic and non-catalytic subunits, as in Arabidopsis. The ZmIDHs significantly differed in physicochemical properties, gene structure, conserved motifs, and protein tertiary structure. Promoter prediction analysis revealed that the promoters of these ZmIDHs contain cis-acting elements associated with light response, abscisic acid, phytohormones, and abiotic stresses. ZmIDH is predicted to interact with proteins involved in development and stress resistance. Expression analysis of public data revealed that most ZmIDHs are specifically expressed in anthers. Different types of ZmIDHs responded to abiotic stresses with different expression patterns, but all exhibited responses to abiotic stresses to some extent. In addition, analysis of the public sequence from transcription data in an association panel suggested that natural variation in ZmIDH1.4 will be associated with drought tolerance in maize. These results suggested that ZmIDHs respond differently and/or redundantly to abiotic stresses during plant growth and development, and this analysis provides a foundation to understand how ZmIDHs respond to drought stress in maize.

Microclaw Array Fabricated by Single Exposure of Femtosecond Airy Beam and Self-Assembly for Regulating Cell Migratory Plasticity.

The highly aligned extracellular matrix of metastatic breast cancer cells is considered to be the "highway" of cancer invasion, which strongly promotes the directional migration of cancer cells to break through the basement membrane. However, how the reorganized extracellular matrix regulates cancer cell migration remains unknown. Here, a single exposure of a femtosecond Airy beam followed by a capillary-assisted self-assembly process was used to fabricate a microclaw-array, which was used to mimic the highly oriented extracellular matrix of tumor cells and the pores in the matrix or basement membrane during cell invasion. Through the experiment, we found that metastatic breast cancer MDA-MB-231 cells and normal breast epithelial MCF-10A cells exhibit three major migration phenotypes on microclaw-array assembled with different lateral spacings: guidance, impasse, and penetration, whereas guided and penetrating migration are almost completely arrested in noninvasive MCF-7 cells. In addition, different mammary breast epithelial cells differ in their ability to spontaneously perceive and respond to the topology of the extracellular matrix at the subcellular and molecular levels, which ultimately affects the cell migratory phenotype and pathfinding. Altogether, we fabricated a microclaw-array as a flexible and high-throughput tool to mimic the extracellular matrix during invasion to study the migratory plasticity of cancer cells.

A Multidimensional Visible Evaluation Model for Stroke Rehabilitation: A Pilot Study.

Efficient rehabilitation state evaluation is important to the design of rehabilitation strategies after stroke. However, most traditional evaluations have depended on subjective clinical scales, which do not entail quantitative evaluation of the motor function. Functional corticomuscular coupling (FCMC) can be used to quantitatively describe the rehabilitation state. However, how to apply FCMC to clinical evaluation still needs to be studied. In this study, we propose a visible evaluation model which can combine the FCMC indicators with a Ueda score to comprehensively evaluate the motor function. In this model, we first calculated the FCMC indicators based on our previous study, including transfer spectral entropy (TSE), wavelet package transfer entropy (WPTE) and multiscale transfer entropy (MSTE). We then apply Pearson correlation analysis to determine which FCMC indicators are significantly correlated with the Ueda score. Then, we simultaneously introduced a radar map to present the selected FCMC indicators and the Ueda score, and described the relation between them. Finally, we calculated the comprehensive evaluation function (CEF) of the radar map and applied it as a comprehensive score of the rehabilitation state. To verify the model's effectiveness, we synchronously collected the electroencephalogram (EEG) and electrocardiogram (EMG) data from stroke patients under the steady-state force task and evaluated the state by the model. This model visualized the evaluation results by constructing a radar map and presented the physiological electrical signal features and the clinical scales at the same time. The CEF indicator calculated from this model was significantly correlated with the Ueda score (P=0.001<0.01). This research provides a new approach to evaluation and rehabilitation training after stroke, and explicates possible pathomechanisms.

Lysosomal quality control: molecular mechanisms and therapeutic implications.

Lysosomes are essential catabolic organelles with an acidic lumen and dozens of hydrolytic enzymes. The detrimental consequences of lysosomal leakage have been well known since lysosomes were discovered during the 1950s. However, detailed knowledge of lysosomal quality control mechanisms has only emerged relatively recently. It is now clear that lysosomal leakage triggers multiple lysosomal quality control pathways that replace, remove, or directly repair damaged lysosomes. Here, we review how lysosomal damage is sensed and resolved in mammalian cells, with a focus on the molecular mechanisms underlying different lysosomal quality control pathways. We also discuss the clinical implications and therapeutic potential of these pathways.

Improving the resilience of power grids against typhoons with data-driven spatial distributionally robust optimization.

In recent years, the increased frequency of natural hazards has led to more disruptions in power grids, potentially causing severe infrastructural damages and cascading failures. Therefore, it is important that the power system resilience be improved by implementing new technology and utilizing optimization methods. This paper proposes a data-driven spatial distributionally robust optimization (DS-DRO) model to provide an optimal plan to install and dispatch distributed energy resources (DERs) against the uncertain impact of natural hazards such as typhoons. We adopt an accurate spatial model to evaluate the failure probability with regard to system components based on wind speed. We construct a moment-based ambiguity set of the failure distribution based on historical typhoon data. A two-stage DS-DRO model is then formulated to obtain an optimal resilience enhancement strategy. We employ the combination of dual reformulation and a column-and-constraints generation algorithm, and showcase the effectiveness of the proposed approach with a modified IEEE 13-node reliability test system projected in the Hong Kong region.

Spatial-temporal NDVI pattern of global mangroves: A growing trend during 2000-2018.

Mangroves are coastal vegetation with high ecological and economic value that are mainly distributed in tropical and subtropical intertidal zones. In the past, they have been degraded by extensive deforestation for agricultural and aquatic land. In recent years, mangroves have been protected and sustainably used through considerable measures of conservation, restoration and afforestation, but the health trends of mangroves during this process are not clear. To identify the mangrove health conditions and dynamics, we investigated the spatial-temporal trends of global mangroves using the Moderate Resolution Imaging Spectroradiometer (MODIS) normalized difference vegetation index (NDVI) dataset during 2000-2018. The results illustrated that 1) Asian mangroves had the highest NDVI values, especially in Southeast Asia (0.80), while the average NDVI of African mangroves was the lowest (0.67). NDVI values higher than 0.80 were mainly located in Southeast Asia and South America, which accounted for 24.0 % and 7.1 % of the global mangrove area, respectively. 2) Globally, the proportion of mangrove forests that increased significantly (23.6 %, p value < 0.05) was approximately twice as large as the significant decrease (10.7 %, p value < 0.05). Asia, where mangroves are widespread, accounts for nearly half of the world's significant increase (10.8 %) and decrease (4.6 %). Generally, the annual average NDVI for global mangroves exhibited a slow increasing trend from 2000 to 2018 (p value = 0.13). 3) The global mangrove NDVI showed a positive correlation with precipitation (Rprep = 0.79, p value < 0.01) and temperature (Rtemp = 0.37, p value < 0.01), while it was inhibited by sea surface salinity (Rsss = -0.45, p value < 0.01) on a scale of 1° of latitude. 4) The results of the overall growth trend of mangroves indicated that global mangrove conservation appeared to achieve initial success, but direct or potential factors, such as salinity stress, natural disasters, small-scale deforestation, construction of coastal facilities, and sea level rise, still threaten the survival of mangroves, leading to a decline in their health status. This study provides information on the health status of mangrove ecosystems and can assist in formulating subsequent conservation and management measures.

Astragalus Polysaccharide Relieves Inflammatory Responses in Guinea Pigs with Allergic Rhinitis via Ameliorating NF-kB-Mediated Treg/Th17 Imbalance.

BACKGROUND: Allergic rhinitis (AR) is regarded as a prevalent and non-infectious inflammation in nasal mucosa, and astragalus polysaccharide (APS) could mitigate inflammation. OBJECTIVES: Herein, this study probed the specific mechanism of APS in inflammatory responses in AR. METHODS: Firstly, AR guinea pig models were established through the stimulation and sensitization of ovalbumin (OVA) and received APS treatment. Changes in nasal symptoms were assessed through counting the sneezing and rubbing times of guinea pigs. The change patterns of OVA-specific immunoglobulin-E (OVA-sIgE), OVA-specific immunoglobulin-G1 (OVA-sIgG1), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in guinea pig serum were identified. Meanwhile, the levels of IL-17, transforming growth factor (TGF)-ß, IL-10, and forkhead box protein P3 (Foxp3) in the guinea pig tissues or serum were examined, and CD25+Foxp3+Treg or CD4+IL17+Th17 cell proportion was detected. Afterwards, nuclear factor-kappa B (NF-kB) expression in guinea pig nasal mucosa tissues were examined. Rescue experiments were designed to probe the role of NF-kB overexpression in inflammatory responses and Treg/Th17 imbalance in AR guinea pigs. RESULTS: APS treatment reduced sneezing and rubbing times of AR guinea pigs and suppressed OVA-sIgE, OVA-sIgG1, TNF-α, and IL-6 levels in guinea pig serum, and meanwhile, increased CD25+Foxp3+Treg cell proportion while reduced CD4+IL17+Th17 cell proportion in AR guinea pig serum or tissues, in a dose-dependent manner. NF-kB was highly-expressed in AR guinea pigs and down-regulated after APS treatment. NF-kB overexpression facilitated inflammatory responses and Treg/Th17 imbalance in AR. CONCLUSION: APS reduced Treg/Th17 imbalance via suppressing NF-kB expression, thereby ameliorating inflammatory responses in AR.

Postpartum depression and major depressive disorder: the same or not? Evidence from resting-state functional MRI.

Background: Although postpartum depression (PPD) and non-peripartum major depressive disorder (MDD) occurring within and outside the postpartum period share many clinical characteristics, whether PPD and MDD are the same or not remains controversial. Methods: The current study was devoted to identify the shared and different neural circuits between PPD and MDD by resting-state functional magnetic resonance imaging data from 77 participants (22 first-episodic drug-naïve MDD, 26 drug-naïve PPD, and 29 healthy controls (HC)). Results: Both the PPD and MDD groups exhibited higher fractional amplitude of low-frequency fluctuation (fALFF) in left temporal pole relative to the HC group; the MDD group showed specifically increased degree centrality in the right cerebellum while PPD showed specifically decreased fALFF in the left supplementary motor area and posterior middle temporal gyrus (pMTG_L), and specifically decreased functional connectivities between pMTG and precuneus and between left subgeneual anterior cingulate cortex (sgACC_L) and right sgACC. Moreover, sgACC and left thalamus showed abnormal regional homogeneity of functional activities between any pair of HC, MDD, and PPD. Conclusions: These results provide initial evidence that PPD and MDD have common and distinct neural circuits, which may facilitate understanding the neurophysiological basis and precision treatment for PPD.

Design of COVID-19 staged alert systems to ensure healthcare capacity with minimal closures.

Community mitigation strategies to combat COVID-19, ranging from healthy hygiene to shelter-in-place orders, exact substantial socioeconomic costs. Judicious implementation and relaxation of restrictions amplify their public health benefits while reducing costs. We derive optimal strategies for toggling between mitigation stages using daily COVID-19 hospital admissions. With public compliance, the policy triggers ensure adequate intensive care unit capacity with high probability while minimizing the duration of strict mitigation measures. In comparison, we show that other sensible COVID-19 staging policies, including France's ICU-based thresholds and a widely adopted indicator for reopening schools and businesses, require overly restrictive measures or trigger strict stages too late to avert catastrophic surges. As proof-of-concept, we describe the optimization and maintenance of the staged alert system that has guided COVID-19 policy in a large US city (Austin, Texas) since May 2020. As cities worldwide face future pandemic waves, our findings provide a robust strategy for tracking COVID-19 hospital admissions as an early indicator of hospital surges and enacting staged measures to ensure integrity of the health system, safety of the health workforce, and public confidence.

Design of COVID-19 Staged Alert Systems to Ensure Healthcare Capacity with Minimal Closures.

Community mitigation strategies to combat COVID-19, ranging from healthy hygiene to shelter-in-place orders, exact substantial socioeconomic costs. Judicious implementation and relaxation of restrictions amplify their public health benefits while reducing costs. We derive optimal strategies for toggling between mitigation stages using daily COVID-19 hospital admissions. With public compliance, the policy triggers ensure adequate intensive care unit capacity with high probability while minimizing the duration of strict mitigation measures. In comparison, we show that other sensible COVID-19 staging policies, including France's ICU-based thresholds and a widely adopted indicator for reopening schools and businesses, require overly restrictive measures or trigger strict stages too late to avert catastrophic surges. As cities worldwide face future pandemic waves, our findings provide a robust strategy for tracking COVID-19 hospital admissions as an early indicator of hospital surges and enacting staged measures to ensure integrity of the health system, safety of the health workforce, and public confidence.

Brain Proteomic Profiling in Intractable Epilepsy Caused by TSC1 Truncating Mutations: A Small Sample Study.

Tuberous sclerosis complex (TSC) is a genetic disease characterized by seizures, mental deficiency, and abnormalities of the skin, brain, kidney, heart, and lungs. TSC is inherited in an autosomal dominant manner and is caused by variations in either the TSC1 or TSC2 gene. TSC-related epilepsy (TRE) is the most prevalent and challenging clinical feature of TSC, and more than half of the patients have refractory epilepsy. In clinical practice, we found several patients of intractable epilepsy caused by TSC1 truncating mutations. To study the changes of protein expression in the brain, three cases of diseased brain tissue with TSC1 truncating mutation resected in intractable epilepsy operations and three cases of control brain tissue resected in craniocerebral trauma operations were collected to perform protein spectrum detection, and then the data-independent acquisition (DIA) workflow was used to analyze differentially expressed proteins. As a result, there were 55 up- and 55 down-regulated proteins found in the damaged brain tissue with TSC1 mutation compared to the control. Further bioinformatics analysis revealed that the differentially expressed proteins were mainly concentrated in the synaptic membrane between the patients with TSC and the control. Additionally, TSC1 truncating mutations may affect the pathway of amino acid metabolism. Our study provides a new idea to explore the brain damage mechanism caused by TSC1 mutations.

MALAT1 Protected the Angiogenesis Function of Human Brain Microvascular Endothelial Cells (HBMECs) Under Oxygen Glucose Deprivation/re-oxygenation (OGD/R) Challenge by Interacting with miR-205-5p/VEGFA Pathway.

Long non-coding RNA MALAT1 was previously revealed to express abnormally in animal and cellular models of stroke, suggesting its indispensable role in stroke. The aims of the present study were to further investigate the functions of MALAT1 and to elucidate the underlying molecular mechanisms. Oxygen glucose deprivation/re-oxygenation (OGD/R) challenge was used in human brain microvascular endothelial cells (HBMECs) to mimic stroke injury in vitro. MALAT1 and miR-205-5p expression levels were evaluated by qRT-PCR. A tube formation assay was employed to verify the angiogenesis of HBMECs. Cell proliferation and apoptosis were evaluated using the ErdU assay and flow cytometry analysis, respectively. The interaction between miR-205-5p and MALAT1 was verified by dual-luciferase reporter assay. MALAT1 and miR-205-5p were both significantly upregulated in the serum of CIS patients and HBMECs under OGD/R, and the tube formation of HBMECs was damaged after OGD/R treatment. Silencing miR-205-5p remarkably promoted HBMEC proliferation and angiogenesis to resist OGD/R injury. Knockdown of MALAT1 markedly inhibited HBMEC proliferation and angiogenesis, and meanwhile promoted apoptosis induced by OGD/R treatment. Most importantly, MALAT1 acted as a competing endogenous RNA (ceRNA) of miR-205-5p via direct bonding with each other in HBMECs under OGD/R damage, indirectly upregulating the downstream targeted gene VEGFA. MALAT1 protected the angiogenesis function of HBMECs under OGD/R conditions by interacting with miR-205-5p/VEGFA pathway.

Evaluating the Therapeutic Effect of Low-Intensity Transcranial Ultrasound on Traumatic Brain Injury With Diffusion Kurtosis Imaging.

BACKGROUND: Low-intensity transcranial ultrasound (LITUS) has a therapeutic effect on traumatic brain injury (TBI). Diffusion kurtosis imaging (DKI) might be able to evaluate the effect changes of injured brain microstructure. PURPOSE: To evaluate the therapeutic effect of LITUS in a moderate TBI rat model with DKI parameters. STUDY TYPE: Prospective case-control animal study. ANIMAL MODEL: Forty-five rats were randomly divided into sham control, TBI, and LITUS treatment groups (n = 15). FIELD STRENGTH/SEQUENCE: Single-shot spin echo echo-planar imaging and fast T2 WI sequences at 3.0T. ASSESSMENT: DKI parameters were obtained on days 1, 7, 14, 21, 28, 35, and 42 after TBI. STATISTICAL TESTS: For the mean kurtosis (MK), axial kurtosis (Ka), and radial kurtosis (Kr) values, groups were compared using a two-way analysis of variance (ANOVA). RESULTS: LITUS inhibited TBI and caused MK values to increase significantly during the early stage (LITUS vs. TBI, day 7, adjusted P < 0.0001) and decrease during the late stage (LITUS vs. TBI, day 42, adjusted P = 0.0156) in the damaged cortex. In the thalamus, the MK value of the TBI group began to rise on day 7, with no change observed in the LITUS group. TBI increases Ka value during the early stage in the cortex and decreases during the late stage in the cortex and thalamus. LITUS inhibited these Ka changes (LITUS vs. TBI, day 7, adjusted P = 0.0014; LITUS vs. TBI, day 42, adjusted P = 0.0026 and 0.0478, respectively, for cortex and thalamus). The Kr value increased slightly during the early stage in the cortex (TBI vs. Sham, day 1, adjusted P = 0.0016). DATA CONCLUSION: The DKI parameter, particularly the MK value, evaluates primary cortical injury as well as the secondary brain injury that could not be detected by conventional T2 WI. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2020;52:520-531.

Resolving Age-Related Differences in Working Memory: Equating Perception and Attention Makes Older Adults Remember as Well as Younger Adults.

OBJECTIVES: Older adults show clear deficits in working memory functioning. Here, we investigate the often-reported decline in focus switching, that is, the ability to shift items from the focus of attention into working memory, and back. Specifically, we examined whether equating subjects on early processing (perception and attention) might ameliorate the deficit. METHOD: We examined 1-Back and 2-Back performance in younger and older adults, with line segments of different orientation as the stimuli. Stimuli were calibrated depending on each individual's 75% threshold for 1-Back performance. Subjects made match/mismatch judgments. RESULTS: After the calibration on 1-Back performance, no age-related differences were found on either accuracy or sensitivity in the 2-Back task. Additionally, when investigating focus-switch trials versus non-focus-switch trials in a random-order 2-Back task, older adults were more efficient at switching the focus of attention than younger adults. DISCUSSION: These results provide evidence for the view that age-related limitations in focus switching in working memory are caused (at least in part) by changes in early processing (perception and attention), suggesting that (at least some of the) age-related differences in working memory functioning may be due to shifts in trade-off between early processing and memory-related processing.

Significant Down-Regulation of Urea Cycle Generates Clinically Relevant Proteomic Signature in Hepatocellular Carcinoma Patients with Macrovascular Invasion.

Vascular invasion is considered as the critical risk factor of hepatocellular carcinoma (HCC). To reveal the molecular mechanisms underlying macrovascular invasion (MaVI) in HCC, we performed an iTRAQ based proteomic study to identify notably dysregulated proteins from eight HCC patients with differential vascular invasion and further confirmed them in the other 53 HCC patients. Forty-seven proteins were found significantly down-regulated in HCC with MaVI. More importantly, 30 of them were not changed in HCC without MaVI. Gene ontology analysis of these 47 proteins shows the top three enriched biological processes are urea cycle, gluconeogenesis, and arginine biosynthetic process. We validated nine remarkably dysregulated candidates in HCC patients with MaVI by Western blot including eight down-regulated proteins (CPS1, ASS1, ASL, ARG1, BHMT, DMGDH, Annexin A6, and CES1) and one up-regulated protein (CKAP4). Furthermore, dysregulation of CPS1, ASL, and ARG1, key enzymes involved in urea cycle, together with Annexin A6 and CES1, major proteins in regulating cholesterol homeostasis and fatty acid ester metabolism, was verified using immunohistochemical staining. The significant down-regulation of urea cycle generates clinically relevant proteomic signature in HCC patients with macrovascular invasion, which may provide possible insights into the molecular mechanisms of metastasis and new therapeutic targets of HCC.

A study for the mechanism of sensory disorder in restless legs syndrome based on magnetoencephalography.

In spite of the relatively high incidence rate, the etiology and pathogenesis of restless legs syndrome (RLS) are still unclear. Long-term drug treatments fail to achieve satisfying curative effects, which is reflected by rebound and augmentation of related symptoms. An electrophysiological endophenotype experiment was done to investigate the mechanism of somatosensory disorder among RLS patients. Together with 15 normal subjects as the control group, with comparable ages and genders to the RLS patients, 15 primitive RLS patients were scanned by Magnetoencephalography (MEG) under natural conditions; furthermore, the somatosensory evoked magnetic field (SEF) with single and paired stimuli, was also measured. Compared to the control group, the SEF intensities of RLS patients' lower limbs were higher, and the paired-pulse depression (PPD) for SEF in RLS patients was attenuated. It was also revealed by time-frequency analysis of somatosensory induced oscillation (SIO) in RLS patients, that 93.3% of somatosensory induced Alpha (8-12 Hz) oscillations were successfully elicited, while 0% somatosensory induced Gamma (30-55 Hz) oscillations were elicited; which was significantly different from the control group. Additionally, in RLS patients exhibit increased excitability of the sensorimotor cortex, a remarkable abnormality existing in early somatosensory gating control (GC) and an attenuated inhibitory interneuron network, which consequently results in a compensatory mechanism through which RLS patients increase their attention-driven lower limb sensory gating control via somatosensory-induced Alpha (8-12 Hz) oscillation. This hyperexcitability, partially due to an electrocortical disinhibition, may have an important therapeutical implication, and become an important target of neuromodulatory interventions.