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Anti-IgLON5 disease is a recently defined autoimmune disorder of the nervous system associated with autoantibodies against IgLON5. Given its broad clinical spectrum and extremely complex pathogenesis, as well as difficulties in its early diagnosis and treatment, anti-IgLON5 disease has become the subject of considerable research attention in the field of neuroimmunology. Anti-IgLON5 disease has characteristics of both autoimmunity and neurodegeneration due to the unique activity of the anti-IgLON5 antibody. Neuropathologic examination revealed the presence of a tauopathy preferentially affecting the hypothalamus and brainstem tegmentum, potentially broadening our understanding of tauopathies. In contrast to that seen with other autoimmune encephalitis-related antibodies, basic studies have demonstrated that IgLON5 antibody-induced neuronal damage and degeneration are irreversible, indicative of a potential link between autoimmunity and neurodegeneration in anti-IgLON5 disease. Herein, we comprehensively review and discuss basic and clinical studies relating to anti-IgLON5 disease to better understand this complicated disorder.

Objective： A detection method was developed for benazolin residual in rape and rapeseed by High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Methods: The rape and rapeseed were extracted with acetonitrile reagent, purified by Pesti Carb-NH2, separated by C18 column, carried out with methanol-ammonium acetate aqueous solution, detected by HPLC-MS/MS. Results: The liner relation was good in the ranger of 0.01~1.00 μg/mL, and the coefficient of determination was 0.999, the limit of detection(LOD) was 0.008 mg/kg, with the limit of quantification (LOQ) of 0.027 mg/kg. At the spiking levels of 0.03, 0.06, 0.15 mg/kg, the recovery rate of the method was 73.3%~91.3%, and RSD was 4.4%~8.1%. Conclusion: The presedent treatment method is easily-conducing, efficient, and highly sensitive and selective, and it can be used to determine benazolin in rape and rapeseed.

Abstract Background Anti-IgLON5 disease is a rare neurological disorder associated with autoantibodies against the neuronal cell adhesion protein, IgLON5. Cellular investigations with human IgLON5 antibodies have suggested an antibody-mediated pathogenesis, but whether human IgLON5 autoantibodies can induce disease symptoms in mice is yet to be shown. Moreover, the effects of anti-IgLON5 autoantibodies on neurons and the precise molecular mechanisms in vivo remain controversial. Methods We investigated the effects of anti-IgLON5 antibodies in vivo and evaluated their long-term effects. We used two independent passive-transfer animal models and evaluated the effects of the antibodies on mouse behaviors at different time points from day 1 until day 30 after IgG infusion. A wide range of behaviors, including tests of locomotion, coordination, memory, anxiety, depression and social interactions were established. At termination, brain tissue was analyzed for human IgG, neuronal markers, glial markers, synaptic markers and RNA sequencing. Results These experiments showed that patient’s anti-IgLON5 antibodies induced progressive and irreversible behavioral deficits in vivo. Notably, cognitive abnormality was supported by impaired average gamma power in the CA1 during novel object recognition testing. Accompanying brain tissue studies showed progressive increase of brain-bound human antibodies in the hippocampus of anti-IgLON5 IgG-injected mice, which persisted 30 days after the injection of patient’s antibodies was stopped. Microglial and astrocyte density was increased in the hippocampus of anti-IgLON5 IgG-injected mice at Day 30. Whole-cell voltage clamp recordings proved that anti-IgLON5 antibodies affected synaptic homeostasis. Further western blot investigation of synaptic proteins revealed a reduction of presynaptic (synaptophysin) and post-synaptic (PSD95 and NMDAR1) expression in anti-IgLON5 IgG-injected mice. Conclusions Overall, our findings indicated an irreversible effect of anti-IgLON5 antibodies and supported the pathogenicity of these antibodies in vivo.

With advancements in modern medical technology, the treatment of rhegmatogenous retinal detachment has been receiving increasing attention. Globally, vitrectomy combined with intraocular silicone oil tamponade has been widely used for rhegmatogenous retinal detachment, and the surgical equipment and technology required are increasingly advanced. In such an operation, it is crucial to understand how to achieve the best therapeutic effect with the minimum amount of silicone oil tamponade so as to reduce surgical complications. Traditional medical methods cannot effectively evaluate the effect of different silicone oil dosages on retinal hole attachment. Aiming at this concern, the current study proposed a silicone oil tamponade simulation method for retinal detachment surgery. Based on physical modeling and computer numerical discretization techniques, the intraocular force and silicone oil filling state were analyzed. Three-dimensional modeling and simulation of the silicone tamponade process were then conducted and visualized to help with medical decision-making. First, the human eyeball and surgical instruments were modeled and sampled to simulate the eyeball state during the operation. Second, based on differences in density, viscosity coefficient, and surface tension between water and silicone oil, the two-phase flow and water‒silicone oil interaction were simulated. Finally, the solid‒liquid interaction model was constructed to assess the movement and injection process of multiphase liquid in the eyeball. The experimental results show that this method can well present the interaction effect of multiphase fluid movement in the eyeball; understand effects such as surface tension, solid–liquid coupling, liquid stratification, and connector effect; and realize the simulation of the silicone oil injection and water drainage processes through the catheter in the intraocular cavity, which provides an effective way to predict the intraocular state after silicone oil filling and assists doctors in the field of operation process planning and effect prediction.

Ginseng is an important medicinal plant benefiting human health for thousands of years. Root disease is the main cause of ginseng yield loss. It is difficult to detect ginseng root disease by manual observation on the changes of leaves, as it takes a long time until symptoms appear on leaves after the infection on roots. In order to detect root diseases at early stages and limit their further spread, an efficient and non-destructive testing (NDT) method is urgently needed. Hyperspectral remote sensing technology was performed in this study to discern whether ginseng roots were diseased. Hyperspectral reflectance of leaves at 325-1,075 nm were collected from the ginsengs with no symptoms on leaves at visual. These spectra were divided into healthy and diseased groups according to the symptoms on roots after harvest. The hyperspectral data were used to construct machine learning classification models including random forest, extreme random tree (ET), adaptive boosting and gradient boosting decision tree respectively to identify diseased ginsengs, while calculating the vegetation indices and analyzing the region of specific spectral bands. The precision rates of the ET model preprocessed by savitzky golay method for the identification of healthy and diseased ginsengs reached 99% and 98%, respectively. Combined with the preliminary analysis of band importance, vegetation indices and physiological characteristics, 690-726 nm was screened out as a specific band for early detection of ginseng root diseases. Therefore, underground root diseases can be effectively detected at an early stage by leaf hyperspectral reflectance. The NDT method for early detection of ginsengs root diseases is proposed in this study. The method is helpful in the prevention and control of root diseases of ginsengs to prevent the reduction of ginseng yield.

Material microstructure data are an important type of data in building intrinsic relationships between compositions, structures, processes, and properties, which are fundamental to material design. Therefore, the quantitative analysis of microstructures is essential for effective control of the material properties and performances of metals or alloys in various industrial applications. Microscopic images are often used to understand the important structures of a material, which are related to certain properties of interest. One of the key steps during material design process is the extraction of useful information from images through microscopic image processing using computational algorithms and tools. For example, image segmentation, which is a task that divides the image into several specific and unique regions, can detect and separate each microstructure to quantitatively analyze its size and shape distribution. This technique is commonly used in extracting significant information from microscopic images in material structure characterization field. With great improvement in computing power and methods, a large number of image segmentation methods based on different theories have made great progress, especially deep learning-based image segmentation method. Therefore selecting an appropriate evaluation method to assess the accuracy and applicability of segmentation results to properly select the optimal segmentation methods and their indications on the direction of future improvement is necessary. In this work, 14 evaluation metrics of image segmentation were summarized and discussed. The metrics were divided into five categories: pixel, intra class coincidence, edge, clustering, and instance based. In the application of material microscopic image analysis, we collected two classical datasets (Al–La alloy and polycrystalline images) to conduct quantitative experiment. The performance of different segmentation methods and different typical noises in different evaluation metrics were then compared and discussed. Finally, we discussed the advantages and applicability of various evaluation metrics in the field of microscopic image processing.

Objective To construct an inflammation-responsive high-density lipoprotein (HDL)-mimetic nanoparticle with anti-atherosclerotic activity using a bioinspired strategy based on a oxidation-responsive material. Methods 4-(hydroxymethyl) phenylboronic acid pinacol ester (PBAP) was chemically conjugated to β-cyclodextrin (β-CD) to synthesize a reactive oxygen species (ROS)-sensitive material.Nanoprecipitation and coextrusion methods were used to prepare HDL-mimetic nanoparticles (mHDL NP).Spectroscopy was employed to verify the structure of the synthesized material, and microscopy was utilized to observe the morphology of the nanoparticles. We observed phagocytosis of the nanoparticles by murine RAW264. 7 macrophages using flow cytometry and confocal microscopy, and examined the release of the inflammatory factors tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) in the supernatant by the macrophages cultured in the presence of the nanoparticles using ELISA. We also used a fluorescent ROS probe DCFH-DA to detect the changes of ROS generated in RAW264. 7 macrophages in response to the nanoparticles. Different methods were used to assess the effects of the nanoparticles on cholesterol efflux and foam cell formation in RAW264. 7 cells. Results Spectroscopy analysis showed that about 5 PBAP units were conjugated to each β-CD molecule. The prepared nanoparticles had a well-defined spherical shape with a narrow size distribution and a mean diameter of about 200 nm. In vitro experiments showed that RAW264. 7 cells phagocytosed the nanoparticles in a time- and dose-dependent manner. mHDL NP significantly inhibited the secretion of the inflammatory factors and ROS production by RAW264. 7 cells in response to inflammatory stimulation (P < 0. 05), which demonstrated potent anti-inflammatory and antioxidant activities of the nanoparticles. mHDL NP time- and concentration-dependently promoted cholesterol efflux(P < 0. 05) and significantly inhibited foam cell formation in RAW264. 7 macrophages. Conclusions We successfully synthesize HDL-mimetic nanoparticles with antioxidant and reverse cholesterol transport capacities. Our preliminary in vitro cellular evaluations demonstrate obvious anti-atherosclerotic activity of the synthesized nanoparticles.

Objective To design and synthesize a new hydrophilic aspartic acid peptide derivative, poly(isopropyl-D, L-aspartamide) (PIPAA), and investigate its efficiency to self-assemble with carboxy-containing therapeutics into pH-sensitive microspheres to enhance the dissolution and oral bioavailability of hydrophobic drugs. Methods With phosphoric acid as the catalyst, D, L-aspartic acid was polymerized into polysuccinimide (PSI) at 180 ℃ followed by ring-opening reaction with isopropylamine to form PIPAA. The successful synthesis of PSI and PIPAA was characterized by Fourier transform infrared spectroscopy (FT-IR) and 1H NMR spectroscopy. The morphology, size, drug loading content and loading efficiency of IND/PIPAA microspheres were characterized. FT-IR and 1H NMR spectroscopy were used to determine non-covalent forces between IND and PIPAA in IND/PIPAA microspheres, and the existence form of IND in IND/PIPAA microspheres was examined by differential scanning calorimetry (DSC) and Xray diffraction (XRD) measurement. We carried out in vitro tests to investigate pH-responsive release profiles of IND/PIPAA microspheres. We also examined plasma concentrations of IND using high-performance liquid chromatogrpahy (HPLC) in rats after oral administration of IND/PIPAA microspheres, and evaluated the anti-inflammatory efficacy of IND/PIPAA microspheres in rats with carrageen-induced paw edema. Results FT-IR and 1H NMR spectra demonstrated successful synthsis of PSI and PIPAA. Morphological observation and size determination revealed a spherical shape and uniform particle size of the IND/PIPAA microspheres, which were self-assembled through electrostatic force, hydrogen bonding, and hydrophobic interactions between IND and PIPAA as confimred by FT-IR and 1H NMR spectra. DSC and XRD measurements indicated that IND molecules entrapped in the microspheres were essentially amorphous. While drug release was almost completely suppressed at a gastric pH level, rapid IND release from the microspheres in vitro was observed at pH 7.4. After oral administration in rats, IND/PIPAA microspheres, as compard with raw IND, obviously enhanced plasma concentrations of IND with a 2.4-fold higher AUC. In rats with carrageen-induced acute inflammation in the paws, IND/PIPAA microspheres exhibited much stronger anti-inflammatory activity than saline (P=0.046) and raw IND (P=0.002). Conclusion The carboxyl-containing hydrophobic drug IND and the hydrophilic aspartic acid peptide derivative PIPAA can self-assemble into well-defined microspheres with a uniform size to serve as an efficient drug delivery system that increases intestinal dissolution of IND to enhance its oral bioavailability and efficacy.

Autoimmune neurologic diseases are a new category of immune-mediated disease demonstrating a widely varied spectrum of clinical manifestations. Recently, sleep disturbances in patients with autoimmune neurologic diseases have been reported to have an immense negative impact on the quality of life. Excessive daytime sleep, rapid eye movement sleep behavior disorder (RBD), and narcolepsy are the most frequent sleep disorders associated with autoimmune neurologic diseases. Sleep disturbances might be the initial symptoms of disease or persist throughout the course of the disease. In this review, we have discussed sleep disturbances in different autoimmune neurologic diseases and their potential pathophysiological mechanisms.

Paraneoplastic amyotrophic lateral sclerosis (ALS) is a rare and special type of ALS. The pathogenesis, clinical presentation, treatment and prognosis remain poorly understood. We herein presented three cases of paraneoplastic ALS. In case 1, we first reported an ALS patient with the positive serum antibodies against both Sry-like high mobility group box 1 (SOX1) and glutamic acid decarboxylase 65 (GAD65). However, immunotherapy did not improve his neurological symptoms. We also reported two ALS patients with renal clear cell carcinoma and chronic myelogenous leukemia. No positive paraneoplastic antibodies were detected in either the serum or the cerebrospinal fluid of the two patients, and their clinical symptoms progressed slowly after tumor treatment. The three cases enriched the existing case pool of this rare disorder. In addition, we have comprehensively reviewed the literature of paraneoplastic ALS. The clinical features, treatment effect and prognosis were summarized to broaden our understanding of paraneoplastic ALS.

The rostromedial tegmental nucleus (RMTg), also called the GABAergic tail of the ventral tegmental area, projects to the midbrain dopaminergic system, dorsal raphe nucleus, locus coeruleus, and other regions. Whether the RMTg is involved in sleep-wake regulation is unknown. In the present study, pharmacogenetic activation of rat RMTg neurons promoted non-rapid eye movement (NREM) sleep with increased slow-wave activity (SWA). Conversely, rats after neurotoxic lesions of 8 or 16 days showed decreased NREM sleep with reduced SWA at lights on. The reduced SWA persisted at least 25 days after lesions. Similarly, pharmacological and pharmacogenetic inactivation of rat RMTg neurons decreased NREM sleep. Electrophysiological experiments combined with optogenetics showed a direct inhibitory connection between the terminals of RMTg neurons and midbrain dopaminergic neurons. The bidirectional effects of the RMTg on the sleep-wake cycle were mimicked by the modulation of ventral tegmental area (VTA)/substantia nigra compacta (SNc) dopaminergic neuronal activity using a pharmacogenetic approach. Furthermore, during the 2-hour recovery period following 6-hour sleep deprivation, the amount of NREM sleep in both the lesion and control rats was significantly increased compared with baseline levels; however, only the control rats showed a significant increase in SWA compared with baseline levels. Collectively, our findings reveal an essential role of the RMTg in the promotion of NREM sleep and homeostatic regulation.

Traditional village culture is an important part of rural culture as well as a precious heritage and historical memory of the Chinese nation, and its effective inheritance and sustainable development have attracted much attention. However, traditional village culture is often in a disadvantaged position in the process of urban-rural cultural exchanges, and the cultural adaptation problem of traditional village residents creates difficulties for the integration of urban-rural culture and the development of traditional cultural inheritance in China. In the context of traditional village conservation and tourism development, the cultural adaptation of traditional village residents is related to the resolution of the contradiction among traditional village development and conservation, the realization of the residents' good life, and the realization of the creative transformation and innovative development of traditional culture. Based on the literature on cultural adaptation, case summaries, and long-term field research experiences, this study clarifies the practical objectives of the cultural adaptation of tourism-driven traditional village residents, refines the process mechanism of their cultural adaptation by combining dimensions and processes, and explores the integration path of cultural adaptation based on positive psychology. The results show that first, the process mechanism of cultural adaptation of the residents of tourism-driven traditional villages can be investigated by combining the context of the evolution of urban-rural relationships in China and the U-curve theory of cultural adaptation. During the period of foreign culture entry, residents' external actions are actively cooperative, although their internal perceptions show foreign culture biases and development opportunity expectations. During the period of cultural clash and adjustment, conflicts and contradictions in daily life and behavioral expressions of residents are frequent, causing negative internal psychological emotions and cultural assimilation. The goal of the cultural integration period is that after a series of conflicts, residents will actively cooperate in their external behavior, and will be able to pass on their culture and seek progress. In terms of internal perceptions, residents will have increased psychological satisfaction, cultural confidence, and positive and open cultural perceptions. Further, borrowing from the research concept of positive psychology, we created a positive social organization system with three aspects: government macro-control, coordination of multiple groups, and a preventive supervision mechanism; a positive personality trait system with three aspects: cross-cultural interaction skills, ownership concept, and flexible and open cultural cognition; and a positive emotional experience system with three aspects: cultural identity, positive gaze of visitors, and community care. Based on the above systems, corresponding countermeasures to be taken at different stages of the cultural adaptation process are proposed to construct an integrated path of cultural adaptation for residents of traditional villages. This study explores the process mechanism and integration path of cultural adaptation of traditional village residents to deepen the interactive logic of locality and cultural adaptation, and provides a scientific reference for community governance and conservation practices in traditional villages, supporting traditional village locality protection and urban-rural integration.