Phase I clinical trial of NH130 and the prediction of its pharmacokinetics using physiologically based pharmacokinetic modeling.

Background: Parkinson's disease psychosis (PDP) is a common and distressing complication of Parkinson's disease (PD), characterized by hallucinations and delusions. This research aimed to assess the pharmacokinetics and safety of NH130, a selective serotonin 5-HT2A inverse agonist, as a potential PDP treatment in healthy individuals. Methods: We conducted clinical pharmacokinetic studies and safety evaluations for NH130, employing a physiologically based pharmacokinetic (PBPK) model to predict its behavior in human body. Results: In a single-dose escalation study, healthy volunteers received NH130 at varying doses (2 mg, 6 mg, 12 mg, 24 mg, 40 mg, 60 mg, and 90 mg) or a placebo. The drug demonstrated favorable pharmacokinetics, with no serious adverse events (AEs) reported. Clinical plasma concentrations correlated well with PBPK model predictions, validating the model's utility for guiding future clinical development. Conclusion: NH130 showed promising pharmacokinetic characteristics and safety profile, supporting its progression to multi-dose trials and suggesting its potential as a therapeutic agent for PDP. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/index.html, Identifier CTR20230409.

Hypolipidemic Effects of Mesona chinensis Benth Polysaccharides with Different Structures and Molecular Weights.

Four novel Mesona chinensis Benth polysaccharides were isolated using aqueous alcohol precipitation. Their molecular weights were determined using high-performance gel permeation chromatography: MA1 (2.3 kDa), MA2 (80.5 kDa), MA3 (180.9 kDa), and MA4 (635.2 kDa), and their compositions were analyzed using GC-MS. The polysaccharides were mainly D-glucose, D-galactose, L-Rhamnose, D-arabinose, D-xylose, and D-mannose. The structural characteristics were further analyzed using infrared spectrophotometry and were identified as a type of pyrrhic sugar. An insulin-induced insulin resistance model of HepG2 cells and oleic acid-induced fat accumulation model of insulin were established to evaluate the hypolipidemic effects. Three Bacteroides spp. [Bacteroides thetaiotaomicron (BT), B. ovatus (BO), and B. cellulosilyticus (BC)] that were negatively correlated with lipid-lowering activity were used to evaluate the lipid-lowering activity of polysaccharides. The Bacteroides metabolites of MA1 and MA2 exhibited hypolipidemic effects and antioxidant activities and could potentially be used as lipid-lowering supplements.

Temporal-spatial deciphering mental subtraction in the human brain.

Mental subtraction, involving numerical processing and operation, requires a complex interplay among several brain regions. Diverse studies have utilized scalp electroencephalograph, electrocorticogram, or functional magnetic resonance imaging to resolve the structure pattern and functional activity during subtraction operation. However, a high resolution of the spatial-temporal understanding of the neural mechanisms involved in mental subtraction is unavailable. Thus, this study obtained intracranial stereoelectroencephalography recordings from 20 patients with pharmacologically resistant epilepsy. Specifically, two sample-delayed mismatch paradigms of numeric comparison and subtracting results comparison were used to help reveal the time frame of mental subtraction. The brain sub-regions were chronologically screened using the stereoelectroencephalography recording for mental subtraction. The results indicated that the anterior cortex, containing the frontal, insular, and parahippocampous, worked for preparing for mental subtraction; moreover, the posterior cortex, such as parietal, occipital, limbic, and temporal regions, cooperated during subtraction. Especially, the gamma band activities in core regions within the parietal-cingulate-temporal cortices mediated the critical mental subtraction. Overall, this research is the first to describe the spatiotemporal activities underlying mental subtraction in the human brain. It provides a comprehensive insight into the cognitive control activity underlying mental arithmetic. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09937-z.

Spatial context scaffolds long-term episodic richness of weaker real-world autobiographical memories in both older and younger adults.

Remembering life experiences involves recalling not only what occurred (episodic details), but also where an event took place (spatial context), both of which decline with age. Although spatial context can cue episodic detail recollection, it is unknown whether initially recalling an event alongside greater reinstatement of spatial context protects memory for episodic details in the long term, and whether this is affected by age. Here, we analysed 1079 personally-experienced, real-world events from 29 older adults and 12 younger adults. Events were recalled first on average 6 weeks after they occurred and then again on average 24 weeks after they occurred. We developed a novel scoring protocol to quantify spatial contextual details and used the established Autobiographical Interview to quantify episodic details. We found improved recall of episodic details after a delay if those details had initially been recalled situated in greater spatial context. Notably, for both older and younger adults, this preservation was observed for memories initially recalled with low, but not high, numbers of episodic details, suggesting that spatial context aided episodic retrieval for memories that required more support. This work supports the notion that spatial context scaffolds detail-rich event recollection and inspires memory interventions that leverage this spatial scaffold.

A machine learning model for identifying systemic lupus erythematosus through laboratory information system and electronic medical record.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Its diagnosis poses significant challenges especially at early stages and in atypical cases. The aim of this study was to develop a machine learning model based on common laboratory tests that can aid SLE diagnosis. METHODS: A standard protocol was developed to collect data of SLE and control immune diseases. A 10-fold cross-validation was performed in the modeling dataset (n=862), and an external dataset (n=198) was used for model validation. Machine learning algorithms were applied to construct a diagnostic model. Performance was evaluated based on area under the curve (AUC) values, F1-score, negative predictive value, positive predictive value, accuracy, sensitivity, and specificity. RESULTS: The optimal model was based on a random forest algorithm with 10 clinical features. Thrombin time, prothrombin activity, and uric acid contributed most to the diagnostic model. The SLE diagnostic model showed sufficient predictive accuracy, with AUC values of 0.8286 in the validation dataset. CONCLUSIONS: Our diagnostic model based on 10 common laboratory tests identified the patients with SLE with high accuracy. An online version of the model can potentially be applied in clinical settings for the differential diagnosis of SLE.

Geometric error modeling and compensation for high precision composite optical measurement systems.

Composite optical measurement systems are widely used in the field of precision measurement due to their combination of inspection with high accuracy, speed, wide range, real-time, and other advantages. Whereas errors are prevalent in measurements, in order to improve detection accuracy, the systems must be compensated for geometric errors in three-dimensional space. Aiming at the complex situation of multi-probes and multi-zooms in the composite optical measurement system, the current error modelling methods are difficult to be directly applied, so this paper establishes a unified three-dimensional volumetric error model based on the theory of multi-body system and combined with the principle of geometric optics, performs the error verification through the direct measurement method, and finally realises the compensation of geometric error in the continuous space of the whole measurement range. Eventually, the accuracy of the proposed error model and the effectiveness of the error compensation method were verified by a laser interferometer and standard objects to be measured, and the integrated geometric error of the system was decreased by 76.55%, which effectively improved the accuracy of the system. The error modelling and compensation method proposed in this paper provides a new idea for the error compensation of the zoom measurement system, and at the same time, it is universal for the measurement systems of different structures and motion forms, which can be widely used in the field of precision measurement.

Automatic aberration compensation for digital holographic microscopy based on bicubic downsampling and improved minimization of global phase gradients.

In digital holographic microscopy, aberrations caused by imperfect optical system settings can greatly affect the quantitative measurement of the target phase, so the compensation of aberrations in the distorted phase has become a key point of research in digital holographic microscopy. Here, we propose a fully automatic numerical phase aberration compensation method with fast computational speed and high robustness. The method uses bicubic downsampling to smooth the sample phase for reducing its disturbance to the background aberration fit, while reducing the computational effort of aberration compensation. Polynomial coefficients of the aberration fitting are iteratively optimized in the process of minimizing the global phase gradient by improving the phase gradient operator and constructing the loss function to achieve accurate fitting of the phase aberration. Simulation and experimental results show that the proposed method can achieve high aberration compensation accuracy without prior knowledge of the hologram recording settings or manual selection of the background area free of samples, and it is suitable for samples with moderate and relatively flat background area, which can be widely used in the quantitative analysis of biological tissues and micro and nano structures.

Metabolomics-based study on the changes of endogenous metabolites during adventitious bud formation from leaf margin of Bryophyllum pinnatum (Lam.) Oken.

Bryophyllum pinnatum (Lam.) Oken is an ornamental and ethno-medicine plant, which can grow a circle of adventitious bud around the leaf margin. The dynamic change of metabolites during the development of B. pinnatum remains poorly understood. Here, leaves from B. pinnatum at four developmental stages were sampled based on morphological characteristics. A non-targeted metabolomics approach was used to evaluate the changes of endogenous metabolites during adventitious bud formation in B. pinnatum. The results showed that differential metabolites were mainly enriched in sphingolipid metabolism, flavone and flavonol biosynthesis, phenylalanine metabolism, and tricarboxylic acid cycle pathway. The metabolites assigned to amino acids, flavonoids, sphingolipids, and the plant hormone jasmonic acid decreased from period Ⅰ to Ⅱ, and then increased from period Ⅲ to Ⅳ with the emergence of adventitious bud (period Ⅲ). While the metabolites related to the tricarboxylic acid cycle showed a trend of first increasing and then decreasing during the four observation periods. Depending on the metabolite changes, leaves may provide conditions similar to in vitro culture for adventitious bud to occur, thus enabling adventitious bud to grow at the leaf edge. Our results provide a basis for illustrating the regulatory mechanisms of adventitious bud in B. pinnatum.

Effect of different plant growth regulators on callus and adventitious shoots induction, polysaccharides accumulation and antioxidant activity of Rhodiola dumulosa.

Objective: As a medicinal plant, the resource of Rhodiola dumulosa is deficient along with the large collection. For the protection and utilization of R. dumulosa, the influence of plant growth regulators (PGRs) on callus induction and adventitious shoots differentiation, polysaccharide production and the antioxidant activity were tested. Methods: Internodes of R. dumulosa were used as explants and cultured on MS medium plus different plant growth regulators (PGRs). The anti-oxidative activities of polysaccharides were evaluated using radical scavenging assays. Results: By response surface plot, 0.85 mg/L N6-benzyladenine (BA), 0.34 mg/L naphthaleneacetic acid (NAA) and 0.33 mg/L 2,4-dicholorophenoxyacetic acid (2,4-D) were the optimal factors for callus induction (90.03%) from internodes explants on MS medium. The fresh weight of green callus increased 47.26 fold, when callus was inoculated on MS + thidiazuron (TDZ) 0.5 mg/L + NAA 2.0 mg/L. Adventitious buds regenerated from callus on the media of MS were fortified with BA 1.0 mg/L plus NAA 0.5 mg/L, and the induction rate was 40.00%. MS plus indole-3-butyric acid (IBA) 1.0 mg/L produced the highest rooting rate with 10 to 15 roots in a length of 2-3 cm per shoot. The content of total polysaccharides in callus developed on MS + TDZ 0.5 mg/L + NAA 2.0 mg/L and MS + BA 1.0 mg/L + NAA 0.5 mg/L was as high as 1.72%-2.15%. At the dose of 0.5 mg/mL polysaccharides extracted from different callus induced on MS + NAA 2.0 mg/L + TDZ 0.5 mg/L or MS + BA 1.0 mg/L + NAA 0.5 mg/L or MS + BA 0.5 mg/L + 2,4-D 0.5 mg/L, the ABTS radical eliminating percentages were 82.78%, 80.18% and 68.59%, respectively, much higher than that of wild plant. Conclusion: A rapid micropropagation system for R. dumulosa has been developed. The combination of TDZ and NAA or BA and NAA can increase the yield of the total polysaccharides. The polysaccharides isolated from callus and whole wild plants had stronger free radicals scavenging activities, indicating that polysaccharides from R. dumulosa are the potential pharmaceutical supplements.

Human anterior thalamic stimulation evoked cortical potentials align with intrinsic functional connectivity.

Characterizing human thalamocortical network is fundamental for understanding a vast array of human behaviors since the thalamus plays a central role in cortico-subcortical communication. Over the past few decades, advances in functional magnetic resonance imaging have allowed for spatial mapping of intrinsic resting-state functional connectivity (RSFC) between both cortical regions and in cortico-subcortical networks. Despite these advances, identifying the electrophysiological basis of human thalamocortical network architecture remains challenging. By leveraging stereoelectroencephalography electrodes temporarily implanted into distributed cortical regions and the anterior nucleus of the thalamus (ANT) of 10 patients with refractory focal epilepsy, we tested whether ANT stimulation evoked cortical potentials align with RSFC from the stimulation site, derived from a normative functional connectome (n = 1000). Our study identifies spatial convergence of ANT stimulation evoked cortical potentials and normative RSFC. Other than connections to the Papez circuit, the ANT was found to be closely connected to several distinct higher-order association cortices, including the precuneus, angular gyrus, dorsal lateral prefrontal cortex, and anterior insula. Remarkably, we found that the spatial distribution and magnitude of cortical-evoked responses to single-pulse electrical stimulation of the ANT aligned with the spatial pattern and strength of normative RSFC of the stimulation site. The present study provides electrophysiological evidence that stimulation evoked electrical activity flows along intrinsic brain networks connected on a thalamocortical level.

A vertigo network derived from human brain lesions and brain stimulation.

Vertigo is a common neurological complaint, which can result in significant morbidity and decreased quality of life. While pathology to peripheral and subtentorial brain structures is a well-established cause of vertigo, cortical lesions have also been linked to vertigo and may lend insight into relevant neuroanatomy. Here, we investigate the supratentorial lesion locations associated with vertigo and test whether they map to a common brain network. We performed a systematic literature search and identified 23 cases of supratentorial brain lesions associated with vertigo. We mapped the lesion locations to a standard brain template and computed the network of brain regions functionally connected to each lesion location, using a 'wiring diagram' of the human brain termed the human connectome (n = 1000). Sensitivity was assessed by identifying the most common connection to lesion locations associated with vertigo, and specificity was assessed through comparison with control lesions associated with symptoms other than vertigo (n = 68). We found that functional connectivity between lesion locations and the bilateral ventral posterior insula was both sensitive (22/23 lesions) and specific (voxel-wise family-wise error-corrected P < 0.05) for lesion-induced vertigo. We computed connectivity with this hub region to define a lesion-based vertigo network, which included regions in the bilateral insula, somatosensory cortex, higher-level visual areas, cingulate sulcus, thalamus and multiple cerebellar regions in the territory of the posterior inferior cerebellar artery. Next, we used stereo-electroencephalography (80 stimulation sites across 17 patients) to test whether stimulation sites associated with vertigo mapped to this same network. We found that 36/42 (86%) of stimulation sites eliciting vertigo fell within the lesion-based vertigo network in contrast to 16/39 (41%) of stimulation sites that did not elicit vertigo. Connectivity between stimulation sites and our lesion-based hub in the ventral posterior insula was also significantly associated with vertigo (P < 0.0001). We conclude that cortical lesions and direct electrical stimulation sites associated with vertigo map to a common brain network, offering insights into the causal neuroanatomical substrate of vertigo.

Double-sided telecentric zoom optical system using adaptive liquid lenses.

In this paper, the adaptive liquid (AL) lenses are introduced into the double-sided telecentric zoom system, which could greatly decrease the mechanical motion group compared with the traditional zoom system, and only one movable aperture stop (STO) is retained. Firstly, this paper derived the Gaussian brackets used in this system, and we found the appropriate screening method to get the suitable initial structure parameters from the solution space. Then we used the lens module design method to create the initial system. Finally, we used CODEV to further optimize the system, and we got an excellent design result, which controlled the telecentricity of both sides within 0.1°, the distortion was controlled within 0.5%, and the MTF of each zoom configuration above 0.3. This optical system has high application potential and value in the field of precision machine vision. The design method proposed in this article can effectively solve the problem that the zoom system using adaptive liquid lenses lacks the initial structure.

Discriminative neural pathways for perception-cognition activity of color and face in the human brain.

Human performance can be examined using a visual lens. The identification of psychophysical colors and emotional faces with perceptual visual pathways may remain invalid for simple detection tasks. In particular, how the visual dorsal and ventral processing streams handle discriminative visual perceptions and subsequent cognition activities are obscure. We explored these issues using stereoelectroencephalography recordings, which were obtained from patients with pharmacologically resistant epilepsy. Delayed match-to-sample paradigms were used for analyzing the processing of simple colors and complex emotional faces in the human brain. We showed that the angular-cuneus gyrus acts as a pioneer in discriminating the 2 features, and dorsal regions, including the middle frontal gyrus (MFG) and postcentral gyrus, as well as ventral regions, such as the middle temporal gyrus (MTG) and posterior superior temporal sulcus (pSTS), were involved in processing incongruent colors and faces. Critically, the beta and gamma band activities between the cuneus and MTG and between the cuneus and pSTS would tune a separate pathway of incongruency processing. In addition, posterior insular gyrus, fusiform, and MFG were found for attentional modulation of the 2 features via alpha band activities. These findings suggest the neural basis of the discriminative pathways of perception-cognition activities in the human brain.

Intracranial direct electrical mapping reveals the functional architecture of the human basal ganglia.

The basal ganglia play a key role in integrating a variety of human behaviors through the cortico-basal ganglia-thalamo-cortical loops. Accordingly, basal ganglia disturbances are implicated in a broad range of debilitating neuropsychiatric disorders. Despite accumulating knowledge of the basal ganglia functional organization, the neural substrates and circuitry subserving functions have not been directly mapped in humans. By direct electrical stimulation of distinct basal ganglia regions in 35 refractory epilepsy patients undergoing stereoelectroencephalography recordings, we here offer currently the most complete overview of basal ganglia functional characterization, extending not only to the expected sensorimotor responses, but also to vestibular sensations, autonomic responses, cognitive and multimodal effects. Specifically, some locations identified responses weren't predicted by the model derived from large-scale meta-analyses. Our work may mark an important step toward understanding the functional architecture of the human basal ganglia and provide mechanistic explanations of non-motor symptoms in brain circuit disorders.

High-precision calibration to zoom lens of optical measurement machine based on FNN.

We proposed a calibration method for high-precision zoom lenses of optical measurement machines based on Fully Connected Neural Network (FNN), using a 5-layer neural network instead of a camera calibration model, to achieve continuous calibration of zoom lenses at any zoom setting by calibrating typical zooms. From the experimental verification, the average calibration error of this method is 9.83×10-4mm and the average measurement error at any zoom setting is 0.01317mm. The overall calibration precision is better than that of Zhang's calibration method and can meet the application requirements of a high-precision optical measurement machine. The method proposed in this paper provided a new solution and a new idea for the calibration of zoom lenses, which can be widely used in the fields of precision parts inspection and machine-vision measurement.

Wheat yield and nitrogen use efficiency enhancement through poly(aspartic acid)-coated urea in clay loam soil based on a 5-year field trial.

The innovation of N fertilizer and N management practices is essential to maximize crop yield with fewer N inputs. A long-term field fertilization experiment was established in 2015 on the North China Plain (NCP) to determine the effects of a control treatment (CN) and the eco-friendly material poly(aspartic acid)-coated urea (PN), applied as a one-time basal application method, on winter wheat yield and N use efficiency at four N application rates: 0 (N0), 63 (N63), 125 (N125), and 188 (N188) kg N ha-1. The results indicated that compared to CN, PN resulted in a significant increase in wheat yield by 9.6% and 9.2% at N63 and N125, respectively, across the three experimental years, whereas no significant (p < 0.05) difference was detected at N188. Leaf area duration (LAD), crop growth rate (CGR), and dry matter accumulation (DMA) increased with increasing N rates, while PN significantly increased LAD and CGR by 5.1%-16.4% and 5.4%-64.3%, respectively, during the anthesis-ripening growth stage and DMA by 13.7% and 10.1% at N63 and N125, respectively, after the anthesis stage compared to CN. During the grain-filling stage, PN significantly increased the kernel maximum grain-filling rate (Gmax) by 21.7% and the kernel weight at the maximum grain-filling rate (Wmax) by 6.7% at N125 compared to CN. Additionally, compared to CN, PN significantly improved the stover and grain N content at harvest and increased NUT, NPFP, and NAE by 5.7%-40.1%, 2.5%-23.3%, and 3.9%-42.8%, respectively, at N63-N125. Therefore, PN applied using a single basal nitrogen fertilizer application method showed promising potential in maintaining a stable wheat yield and increasing N use efficiency with a 33% urea cut (approximately 63 kg N ha-1) compared to CN at the current wheat yield level on the NCP.

Ultrasonic Characteristics Improve Prediction of Central Lymph Node Metastasis in cN0 Unifocal Papillary Thyroid Cancer.

Background: Prediction of central lymph node metastasis (CLNM) is vital for clinical decision-making processes in clinically N0 (cN0) unifocal papillary thyroid carcinoma (PTC), but the sensitivity of preoperative detection of CLNM is limited. The aim of the present study was to determine whether there are ultrasonic (US) characteristics associated with CLNM. Methods: In total, 1657 PTC patients (514 men and 1143 women) were enrolled in the present study between January 2018 and May 2021. The patients met the following inclusion criteria based on preoperative detection: suspected nodule confirmed as PTC by biopsy; the nodule was unifocal and less than 4 cm in diameter; no prior neck radiation exposure; no extrathyroidal extension; and no CLNM or distant metastases on imaging. All the enrolled patients underwent total thyroidectomy with prophylactic central lymph node dissection (CLND). A postoperative pathological diagnosis was made. Results: CLNM was found in 58.4% of male patients and 36.9% of female patients. In univariate analysis, size, adjacent anterior capsule, distance to the lower pole and color Doppler flow imaging (CDFI) were considered risk factors for the male and female groups (p < 0.05). In multivariate analyses, size, adjacent anterior capsule, distance to the lower pole and CDFI were independent risk factors for male patients. For females, the independent risk factors included size, adjacent anterior capsule, distance to the lower pole and CDFI. Conclusion: In the present cohort, US imaging characteristics, including size, adjacent anterior capsule, distance to the lower pole and CDFI, were identified to be potentially beneficial in preoperative clinical decision-making processes for cN0 unifocal PTC patients.

Distinct Patterns of Automatic and Controlled Incongruent Information Processing in the Human Brain.

It is a fundamental ability to discriminate incongruent information in daily activity. However, the underlying neural dynamics are still unclear. Using stereoelectroencephalography (SEEG), in this study, we investigated the fine-grained and different states of incongruent information processing in patients with refractory epilepsy who underwent intracranial electrode implantation. All patients performed a delayed match-to-sample paradigm in the sequential pairs of visual stimuli (S1 followed by S2). Participants were asked to discriminate whether the relevant feature of S2 was identical to S1 while ignoring the irrelevant feature. The spatiotemporal cortical responses evoked by different conditions were calculated and compared, respectively, in the context of brain intrinsic functional networks. In total, we obtained SEEG recordings from 241 contacts in gray matter. In the processing of irrelevant incongruent information, the activated brain areas included the superior parietal lobule, supramarginal gyrus, angular gyrus, inferior temporal gyrus, and fusiform gyrus. By comparing the relevant incongruent condition with the congruent condition, the activated brain areas included the middle frontal gyrus, superior temporal gyrus, middle temporal gyrus, posterior superior temporal sulcus, and posterior cingulate cortex. We demonstrated the dynamics of incongruent information processing with high spatiotemporal resolution and suggested that the process of automatic detection of irrelevant incongruent information requires the involvement of local regions and relatively few networks. Meanwhile, controlled discrimination of relevant incongruent information requires the participation of extensive regions and a wide range of nodes in the network. Furthermore, both the frontoparietal control network and default mode network were engaged in the incongruent information processing.

Repetitive transcranial magnetic stimulation to treat benign epilepsy with centrotemporal spikes.

OBJECTIVES: To investigate the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on patients with benign epilepsy with centrotemporal spikes (BECTS). METHODS: In this open pilot study, we enrolled four BECTS patients who had frequent seizures (at least 3 seizures during the 3-month baseline). After localizing sources of interictal epileptiform discharges (IEDs) with magnetoencephalography, IEDs-source-rTMS (1 Hz) with 500 pulses at 90% of resting motor threshold was applied for 10 weekdays in each patient. The primary outcome measure was the seizure-reduction rate after rTMS. Other outcome measures were the spike-wave index (SWI), behavioral evaluation, and adverse effects. RESULTS: All four patients received at least 3 months seizure-free after rTMS. Compared with baseline, SWI decreased significantly after rTMS in three patients (patient 1, 3 and 4) (P = .002, P = .007, and P < .001, respectively). Attention deficit identified in two patients in baseline recovered to the normal range after rTMS. No adverse effect was observed. DISCUSSION: Our preliminary observation provides a promising approach to reducing clinical seizures for BECTS with frequent seizures. Of importance, our data may provide a potentially novel method for the high prevalence of behavioral problems in BECTS patients via decreasing cortical hyperexcitability.

Large-range and high-precision autofocus method based on an annular DOE for a laser direct writing system.

We present a large-range and high-precision autofocus method based on an annular diffractive optical element (DOE) for a laser direct writing system. By analyzing the shape of the return spot, the defocus direction and the defocus amount can be obtained at the same time. The experimental results show that the linear detection range of the proposed method can reach at least 76 µm, the sensitivity can reach 100 nm, the detection accuracy can reach 100 nm, and the noise fluctuation does not exceed 50 nm. Apparently, with the advantages of a large detection range, high detection, and good stability, the automatic focus detection method proposed in this paper can be widely applied in various wafer-scale complex microstructure preparation systems.