Changes in the Range of Four Advantageous Grasshopper Habitats in the Hexi Corridor under Future Climate Conditions.

Angaracris rhodopa (Fischer et Walheim), Calliptamus abbreviatus (Ikonnikov), Myrmeleotettix palpalis (Zubowsky), and Oedaleus decorus asiaticus (Bey-Bienko) are the main grasshoppers that harm the natural grassland in the Hexi Corridor in Gansu, northwest China. In this study, the MaxEnt model was employed to identify the key environmental factors affecting the distribution of the four grasshoppers' habitats and to assess their distribution under current and future climate conditions. The aim was to provide a basis for grasshopper monitoring, prediction, and precise control. In this study, distribution of suitable habitats for A. rhodopa, C. abbreviates, M. palpalis, O. decorus asiaticus were predicted under current and future climatic scenarios using the Maxent model. The average AUC (area under the ROC curve) and TSS (true skill statistic) values of the four grasshoppers were greater than 0.9, and the simulation results were excellent and highly reliable. The mean annual precipitation was the main factor limiting the current range of suitable areas for these four species. Under the current climate, A. rhodopa, C. abbreviatus, and O. decorus asiaticus were mainly distributed in the central and eastern parts of the Hexi Corridor, and M. palpalis was distributed throughout the Hexi Corridor, with a suitable area of 1.29 × 104, 1.43 × 104, 1.44 × 104, and 2.12 × 104 km2, accounting for 13.7%, 15.2%, 15.3%, and 22.5% of the total area of the grasslands in the Hexi Corridor, respectively. The highly suitable areas of A. rhodopa, C. abbreviatus, and O. decorus asiaticus were mainly distributed in the eastern-central part of Zhangye City, the western part of Wuwei City, and the western and southern parts of Jinchang City, with areas of 0.20 × 104, 0.29 × 104, and 0.35 × 104 km2, accounting for 2.2%, 3%, and 3.7% of the grassland area, respectively. The high habitat of M. palpalis was mainly distributed in the southeast of Jiuquan City, the west, middle, and east of Zhangye City, the west of Wuwei City, and the west and south of Jinchang City, with an area of 0.32 × 104 km2, accounting for 3.4% of the grassland area. In the 2030s, the range of A. rhodopa, C. abbreviatus, and O. decorus asiaticus was predicted to increase; the range of M. palpalis will decrease. The results of this study could provide a theoretical basis for the precise monitoring and control of key areas of grasshoppers in the Hexi Corridor.

Pro-vasculogenic Fibers by PDA-Mediated Surface Functionalization Using Cell-Free Fat Extract (CEFFE).

Formation of adequate vascular network within engineered three-dimensional (3D) tissue substitutes postimplantation remains a major challenge for the success of biomaterials-based tissue regeneration. To better mimic the in vivo angiogenic and vasculogenic processes, nowadays increasing attention is given to the strategy of functionalizing biomaterial scaffolds with multiple bioactive agents. Aimed at engineering electrospun biomimicking fibers with pro-vasculogenic capability, this study was proposed to functionalize electrospun fibers of polycaprolactone/gelatin (PCL/GT) by cell-free fat extract (CEFFE or FE), a newly emerging natural "cocktail" of cytokines and growth factors extracted from human adipose tissue. This was achieved by having the electrospun PCL/GT fiber surface coated with polydopamine (PDA) followed by PDA-mediated immobilization of FE to generate the pro-vasculogenic fibers of FE-PDA@PCL/GT. It was found that the PDA-coated fibrous mat of PCL/GT exhibited a high FE-loading efficiency (∼90%) and enabled the FE to be released in a highly sustained manner. The engineered FE-PDA@PCL/GT fibers possess improved cytocompatibility, as evidenced by the enhanced cellular proliferation, migration, and RNA and protein expressions (e.g., CD31, vWF, VE-cadherin) in the human umbilical vein endothelial cells (huvECs) used. Most importantly, the FE-PDA@PCL/GT fibrous scaffolds were found to enormously stimulate tube formation in vitro, microvascular development in the in ovo chick chorioallantoic membrane (CAM) assay, and vascularization of 3D construct in a rat subcutaneous embedding model. This study highlights the potential of currently engineered pro-vasculogenic fibers as a versatile platform for engineering vascularized biomaterial constructs for functional tissue regeneration.

Local and Remote Chemogenetic Suppression of Hippocampal Seizures in Rats.

BACKGROUND: Innovative treatments of refractory epilepsy are widely desired, for which chemogenetic technology can provide region- and cell-type-specific modulation with relative noninvasiveness. OBJECTIVES: We aimed to explore the specific applications of chemogenetics for locally and remotely networks controlling hippocampal seizures. METHODS: A virus coding for a modified human Gi-coupled M4 muscarinic receptor (hM4Di) on pyramidal cells was injected into either the right hippocampal CA3 or the bilateral anterior nucleus of the thalamus (ANT) in rats. After one month, seizures were induced by 4-aminopyridine (4-AP) injection into the right CA3. Simultaneously, clozapine-N-oxide (CNO) (2.5 mg/kg) or clozapine (0.1 mg/kg), the specific ligands acting on hM4Di, were injected intraperitoneally. We also set up hM4Di control and clozapine control groups to eliminate the influence of viral transfection and the ligand alone on the experimental results. RESULTS: For both local and remote controls, the mean seizure duration was significantly reduced upon ligand application in the experimental groups. Seizure frequency, on the other hand, only showed a significant decrease in local control, with a lower frequency in the clozapine group than in the CNO group. Both the effects of CNO and clozapine were time-dependent, and clozapine was faster than CNO in local seizure control. CONCLUSION: This study shows the potency of chemogenetics to attenuate hippocampal seizures locally or remotely by activating the transfected hM4Di receptor with CNO or clozapine. ANT is suggested as a potentially safe chemogenetic application target in the epileptic network for focal hippocampal seizures.

Physiological cyclic stretching potentiates the cell-cell junctions in vascular endothelial layer formed on aligned fiber substrate.

In vascular tissue engineering, formation of stable endothelial cell-cell and cell-substrate adhesions is essential for maintaining long-term patency of the tissue-engineered vascular grafts (TEVGs). In this study, sheet-like aligned fibrous substrates of poly(l-lactide-co-caprolactone) (PLCL) were prepared by electrospinning to provide basement membrane-resembling structural support to endothelial cells (ECs). Cyclic stretching at physiological and pathological levels was then applied to human umbilical vein endothelial cells (HUVECs) cultured on chosen fibrous substrate using a force-loading device, from which effects of the cyclic stretching on cell-cell and cell-substrate adhesions were examined. It was found that applying uniaxial 1 Hz cyclic stretch at physiological levels (5 % and 10 % elongation) strengthened the cell-cell junctions, thus leading to improved structural integrity, functional expression and resistance to thrombin-induced damaging impacts in the formed endothelial layer. The cell-cell junctions were disrupted at pathological level (15 % elongation) cyclic stretching, which however facilitated the formation of focal adhesions (FAs) at cell-substrate interface. Mechanistically, the effects of cyclic stretching on endothelial cell-cell and cell-substrate adhesions were identified to be correlated with the RhoA/ROCK signaling pathway. Results from this study highlight the relevance between applying dynamic mechanical stimulation and maintaining the structural integrity of the formed endothelial layer, and implicate a necessity to implement appropriate dynamic mechanical training (i.e., preconditioning) to obtain tissue-engineered blood vessels with long-term patency post-implantation.

Folate-chitosan Coated Quercetin Liposomes for Targeted Cancer Therapy.

BACKGROUND: Although quercetin exhibits promising anti-tumor properties, its clinical application is limited due to inherent defects and a lack of tumor targeting. OBJECTIVE: This study aimed to prepare and characterize active targeting folate-chitosan modified quercetin liposomes (FA-CS-QUE-Lip), and its antitumor activity in vitro and in vivo was also studied. METHODS: Box-Behnken Design (BBD) response surface method was used to select the optimal formulation of quercetin liposomes (QUE-LP). On this basis, FA-CS-QUE-LP was obtained by connecting folic acid chitosan complex (FA-CS) and QUE-LP. The release characteristics in vitro of QUE-LP and FA-CS-QUE-LP were studied. Its inhibitory effects on HepG2 cells were studied by the MTT method. The pharmacokinetics and pharmacodynamics in vivo were studied in healthy Wistar mice and S180 tumor-bearing mice, respectively. RESULTS: The average particle size, zeta potential and encapsulation efficiency of FA-CS-QUELP were 261.6±8.5 nm, 22.3±1.7 mV, and 98.63±1.28 %, respectively. FA-CS-QUE-LP had a sustained release effect and conformed to the Maloid-Banakar release model (R2=0.9967). The results showed that FA-CS-QUE-LP had higher inhibition rates on HepG2 cells than QUE-Sol (P<0.01). There was a significant difference in AUC, t1/2, CL and other pharmacokinetic parameters among QUE-LP, FA-CS-QUE-LP, and QUE-Sol (P<0.05). In in vivo antitumor activity study, the weight inhibition rate and volume inhibition rate of FA-CS-QUE-LP were 30.26% and 37.35%, respectively. CONCLUSION: FA-CS-QUE-LP exhibited a significant inhibitory effect on HepG2 cells, influenced the pharmacokinetics of quercetin in mice, and demonstrated a certain inhibitory effect on S180 tumor-bearing mice, thus offering novel avenues for cancer treatment.

Identification of potential prognostic biomarkers in vulval squamous cell carcinoma based on human papillomavirus infection Status-Analysis of GSE183454.

This study aimed to elucidate the differences in vulval squamous cell carcinomas (VSCC) based on the HPV infection status. The sequencing data GSE183454 which contains 23 VSCC samples based on its HPV infection status was obtained from the Gene Expression Omnibus (GEO) database. We comprehensively dissected the differences of genomic and tumour microenvironment (TME) immune cell infiltration landscapes between HPV + and HPV- VSCC. The potential molecular mechanisms of prognostic genes were explored by functional enrichment analysis. Five novel key molecules (SYCP2, SMC1B, RNF212, MAJIN and C14orf39) with significantly up-regulated expression in HPV + VSCC were identified while protein-protein interaction (PPI) networks were created upon Cytoscape software. Additionally, VSCC with up-regulated expression of these key molecules exhibited a significantly decreased TME immune cell infiltration. SYCP2 is overexpressed in HPV + VSCC and could be a candidate therapy target for further research.IMPACT STATEMENTWhat is already known on this subject? VSCC are characterised by two aetiological pathways. The former occurs in the background of lichen sclerosus, while the latter is related to HPV infection. VSCC most commonly arises from the non-HPV related pathway portends worse prognosis than VSCC derived from HPV infection.What do the results of this study add? Five key molecules are identified and significantly up-regulated in HPV + VSCC. In which, SYCP2 is overexpressed in HPV + VSCC and exhibited a significantly decreased TME immune cell infiltration. SYCP2 constant expression could be a potential biomarker of neoplasms associated with HPV and could be a candidate therapy target in VSCC especially HPV + VSCC for further research.What are the implications of these findings for clinical practice and/or further research? SYCP2 could be a candidate therapy target in VSCC especially with HPV + for further research.

Formation of low-density electrospun fibrous network integrated mesenchymal stem cell sheet.

Cell sheets combined with electrospun fibrous mats represent an attractive approach for the repair and regeneration of injured tissues. However, the conventional dense electrospun mats as supportive substrates in forming "cell sheet on fiber mat" complexes suffer from problems of limiting the cellular function and eliciting a host response upon implantation. To give full play to the role of electrospun biomimicking fibers in forming quality cell sheets, this study proposed to develop a cell-fiber integrated sheet (CFIS) featuring a spatially homogeneous distribution of cells within the fiber structure by using a low-density fibrous network for cell sheet formation. A low-density electrospun polycaprolactone (PCL) fibrous network at a density of 103.8 ± 16.3 µg cm-2 was produced by controlling the fiber deposition for a short period of 1 min and subsequently transferred onto polydimethylsiloxane rings for facilitating cell sheet formation, in which rat bone marrow-derived mesenchymal cells were used. Using a dense electrospun PCL fibrous mat (481.5 ± 7.5 µg cm-2) as the control, it was found that cells on the low-density fibrous network (L-G) exhibited improved capacities in spreading, proliferation, stemness maintenance and matrix-remodeling during the process of CFIS formation. Structurally, the CFIS constructs revealed strong integration between the cells and the fibrous network, thus providing excellent cohesion and physical integrity to enable strengthening of the formed cell sheet. By contrast, the cell sheet formed on the dense fibrous mat (D-G) showed a two-layer (biphasic) structure due to the limitation of cellular invasion. Moreover, such engineered CFIS was identified with enhanced immunomodulatory effects by promoting LPS-stimulated macrophages towards an M2 phenotype in vitro. Our results suggest that the CFIS may be used as a native tissue equivalent "cell sheet" for improving the efficacy of the tissue engineering approach for the repair and regeneration of impaired tissues.

Imbalance between the function of Na+-K+-2Cl and K+-Cl impairs Cl- homeostasis in human focal cortical dysplasia.

Objective: Altered expression patterns of Na+-K+-2Cl- (NKCC1) and K+-Cl- (KCC2) co-transporters have been implicated in the pathogenesis of epilepsy. Here, we assessed the effects of imbalanced NKCC1 and KCC2 on γ-aminobutyric acidergic (GABAergic) neurotransmission in certain brain regions involved in human focal cortical dysplasia (FCD). Materials and methods: We sought to map a micro-macro neuronal network to better understand the epileptogenesis mechanism. In patients with FCD, we resected cortical tissue from the seizure the onset zone (SOZ) and the non-seizure onset zone (non-SOZ) inside the epileptogenic zone (EZ). Additionally, we resected non-epileptic neocortical tissue from the patients with mesial temporal lobe epilepsy (MTLE) as control. All of tissues were analyzed using perforated patch recordings. NKCC1 and KCC2 co-transporters expression and distribution were analyzed by immunohistochemistry and western blotting. Results: Results revealed that depolarized GABAergic signals were observed in pyramidal neurons in the SOZ and non-SOZ groups compared with the control group. The total number of pyramidal neurons showing GABAergic spontaneous postsynaptic currents was 11/14, 7/17, and 0/12 in the SOZ, non-SOZ, and control groups, respectively. The depolarizing GABAergic response was significantly dampened by the specific NKCC1 inhibitor bumetanide (BUM). Patients with FCD exhibited higher expression and internalized distribution of KCC2, particularly in the SOZ group. Conclusion: Our results provide evidence of a potential neurocircuit underpinning SOZ epileptogenesis and non-SOZ seizure susceptibility. Imbalanced function of NKCC1 and KCC2 may affect chloride ion homeostasis in neurons and alter GABAergic inhibitory action, thereby contributing to epileptogenesis in FCDs. Maintaining chloride ion homeostasis in the neurons may represent a new avenue for the development of novel anti-seizure medications (ASMs).

Elevated ApoB/ApoA-I ratio is associated with acute anti-N-Methyl-D-aspartate receptor encephalitis, but not disease outcomes.

Objective: The purpose of the present study is to clarify the relationship between the apolipoprotein B100/apolipoprotein A-I (ApoB/ApoA-I) ratio and anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Methods: A total of 71 patients with anti-NMDAR encephalitis were included in this study, and their ApoB/ApoA-I ratios in baseline and follow-up were retrospectively analyzed. Results: The ApoB/ApoA-I ratio was closely correlated with the baseline-modified Rankin scale (mRS) score of >3 in patients with anti-NMDAR encephalitis. A subgroup analysis showed obvious differences between the high and low ApoB/ApoA-I ratio groups. The ApoB/ApoA-I ratio was positively correlated with intensive care unit (ICU) treatment, length of hospital stay, baseline mRS score, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The ratios of the high and low ApoB/ApoA-I groups both improved in the follow-up. Conclusion: The increased ApoB/ApoA-I ratio is associated with acute anti-NMDAR encephalitis, but not disease outcomes. Serum ApoB/ApoA-I ratio was related to inflammation and immunity in peripheral blood. The findings might provide a new idea for further exploration of the pathogenesis and treatment of anti-NMDAR encephalitis.

The Validation of Deep Learning-Based Grading Model for Diabetic Retinopathy.

Purpose: To evaluate the performance of a deep learning (DL)-based artificial intelligence (AI) hierarchical diagnosis software, EyeWisdom V1 for diabetic retinopathy (DR). Materials and Methods: The prospective study was a multicenter, double-blind, and self-controlled clinical trial. Non-dilated posterior pole fundus images were evaluated by ophthalmologists and EyeWisdom V1, respectively. The diagnosis of manual grading was considered as the gold standard. Primary evaluation index (sensitivity and specificity) and secondary evaluation index like positive predictive values (PPV), negative predictive values (NPV), etc., were calculated to evaluate the performance of EyeWisdom V1. Results: A total of 1,089 fundus images from 630 patients were included, with a mean age of (56.52 ± 11.13) years. For any DR, the sensitivity, specificity, PPV, and NPV were 98.23% (95% CI 96.93-99.08%), 74.45% (95% CI 69.95-78.60%), 86.38% (95% CI 83.76-88.72%), and 96.23% (95% CI 93.50-98.04%), respectively; For sight-threatening DR (STDR, severe non-proliferative DR or worse), the above indicators were 80.47% (95% CI 75.07-85.14%), 97.96% (95% CI 96.75-98.81%), 92.38% (95% CI 88.07-95.50%), and 94.23% (95% CI 92.46-95.68%); For referral DR (moderate non-proliferative DR or worse), the sensitivity and specificity were 92.96% (95% CI 90.66-94.84%) and 93.32% (95% CI 90.65-95.42%), with the PPV of 94.93% (95% CI 92.89-96.53%) and the NPV of 90.78% (95% CI 87.81-93.22%). The kappa score of EyeWisdom V1 was 0.860 (0.827-0.890) with the AUC of 0.958 for referral DR. Conclusion: The EyeWisdom V1 could provide reliable DR grading and referral recommendation based on the fundus images of diabetics.

Engineering a Mechanoactive Fibrous Substrate with Enhanced Efficiency in Regulating Stem Cell Tenodifferentiation.

Electrospun-aligned fibers in ultrathin fineness have previously demonstrated a limited capacity in driving stem cells to differentiate into tendon-like cells. In view of the tendon's mechanoactive nature, endowing such aligned fibrous structure with mechanoactivity to exert in situ mechanical stimulus by itself, namely, without any forces externally applied, is likely to potentiate its efficiency of tenogenic induction. To test this hypothesis, in this study, a shape-memory-capable poly(l-lactide-co-caprolactone) (PLCL) copolymer was electrospun into aligned fibrous form followed by a "stretching-recovery" shape-programming procedure to impart shape memory capability. Thereafter, in the absence of tenogenic supplements, human adipose-derived stem cells (ADSCs) were cultured on the programmed fibrous substrates for a duration of 7 days, and the effects of constrained recovery resultant stress-stiffening on cell morphology, proliferation, and tenogenic differentiation were examined. The results indicate that the in situ enacted mechanical stimulus due to shape memory effect (SME) did not have adverse influence on cell viability and proliferation, but significantly promoted cellular elongation along the direction of fiber alignment. Moreover, it revealed that tendon-specific protein markers such as tenomodulin (TNMD) and tenascin-C (TNC) and gene expression of scleraxis (SCX), TNMD, TNC, and collagen I (COL I) were significantly upregulated on the mechanoactive fibrous substrate with higher recovery stress compared to the counterparts. Mechanistically, the Rho/ROCK signaling pathway was identified to be involved in the substrate self-actuation-induced enhancement in tenodifferentiation. Together, these results suggest that constrained shape recovery stress may be employed as an innovative loading modality to regulate the stem cell tenodifferentiation by presenting the fibrous substrate with an aligned tendon-like topographical cue and an additional mechanoactivity. This newly demonstrated paradigm in modulating stem cell tenodifferentiation may improve the efficacy of tendon tissue engineering strategy for tendon healing and regeneration.

Simple and effective serum biomarkers potential for predicting status epilepticus in anti-N-methyl-D-aspartate receptor encephalitis.

BACKGROUND: Patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis who also present with status epilepticus (SE) often have a poor prognosis. The aim of this study is to explore simple and effective predictors for anti-NMDAR encephalitis accompanied with SE. METHODS: We retrospectively analyzed 65 anti-NMDAR encephalitis patients from January 2015 to December 2018 who admitted to the Third Affiliated Hospital of Sun Yat-sen University. Patients were divided into SE group and non-SE groups. Their pre-treatment data and 3-month follow-up data were retrospectively analyzed. RESULTS: The results showed that compared with the non-SE group, the levels of serum uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) in anti-NMDAR encephalitis patients with SE decreased significantly before treatment. Additionally, the levels of serum UA and HDL-C increased while the level of C-reactive protein (CRP) decreased 3 months after treatment in the SE group. Compared with the non-SE group, the SE patients had higher modified Rankin scale (mRS) scores before (mRS1) and after treatment (mRS2). Serum UA concentrations before treatment showed significantly negative correlations with mRS1 (r = - 0.407, p < 0.01) and mRS2 (r = - 0.458, p < 0.001), while the level of serum CRP before treatment had strong positive correlations with mRS1 (r = 0.304, p < 0.05) and mRS2 (r = 0.301, p < 0.05) in anti-NMDAR encephalitis patients. The receiver operating characteristic curve demonstrated that the combined detection of UA, HDL-C and CRP before treatment had a significantly higher value (the area under the curve = 0.848; 95% confidence interval [CI], 0.74-0.957; p < 0.001) to predict anti-NMDAR encephalitis accompanied with SE than that of single detection. CONCLUSIONS: Hence, the combined detection of serum UA, HDL-C and CRP before treatment may be simple and effective indicators for predicting SE in anti-NMDAR encephalitis, which may be helpful in early stages to remind clinicians to be alert to the emergence of SE.

Mechanistic Analysis of Micro-Neurocircuits Underlying the Epileptogenic Zone in Focal Cortical Dysplasia Patients.

We aim to explore the microscopic neurophysiology of focal cortical dysplasia (FCD) induced epileptogenesis in specific macroscopic brain regions, therefore mapping a micro-macro neuronal network that potentially indicates the epileptogenic mechanism. Epileptic and relatively non-epileptic temporal neocortex specimens were resected from FCD and mesial temporal lobe epilepsy (mTLE) patients, respectively. Whole-cell patch-clamping was performed on cells from the seizure onset zone (SOZ) and non-SOZ inside the epileptogenic zone (EZ) of FCD patients, as well as the non-epileptic neocortex of mTLE patients. Microscopic data were recorded, including membrane characteristics, spontaneous synaptic activities, and evoked action potentials. Immunohistochemistry was also performed on parvalbumin-positive (PV+) interneurons. We found that SOZ interneurons exhibited abnormal neuronal expression and distribution as well as reduced overall function compared with non-SOZ and mTLE interneurons. The SOZ pyramidal cells experienced higher excitation but lower inhibition than the mTLE controls, whereas the non-SOZ pyramidal cells exhibited intermediate excitability. Action potential properties of both types of neurons also suggested more synchronized neuronal activity inside the EZ, particularly inside the SOZ. Together, our research provides evidence for a potential neurocircuit underlying SOZ epileptogenesis and non-SOZ seizure susceptibility. Further investigation of this microscopic network may promote understanding of the mechanism of FCD-induced epileptogenesis.

Automated detection of severe diabetic retinopathy using deep learning method.

PURPOSE: The purpose of this study is to develop and validate the intelligent diagnosis of severe DR with lesion recognition based on color fundus photography. METHODS: The Kaggle public dataset for DR grading is used in the project, including 53,576 fundus photos in the test set, 28,101 in the training set, and 7,025 in the validation set. We randomly select 4,192 images for lesion annotation. Inception V3 structure is adopted as the classification algorithm. Both 299 × 299 pixel images and 896 × 896 pixel images are used as the input size. ROC curve, AUC, sensitivity, specificity, and their harmonic mean are used to evaluate the performance of the models. RESULTS: The harmonic mean and AUC of the model of 896 × 896 input are higher than those of the 299 × 299 input model. The sensitivity, specificity, harmonic mean, and AUC of the method with 896 × 896 resolution images as input for severe DR are 0.925, 0.907, 0.916, and 0.968, respectively. The prediction error mainly occurs in moderate NPDR, and cases with more hard exudates and cotton wool spots are easily predicted as severe cases. Cases with preretinal hemorrhage and vitreous hemorrhage are easily identified as severe cases, and IRMA is the most difficult lesion to recognize. CONCLUSIONS: We have studied the intelligent diagnosis of severe DR based on color fundus photography. This artificial intelligence-based technology offers a possibility to increase the accessibility and efficiency of severe DR screening.

Constipation induced gut microbiota dysbiosis exacerbates experimental autoimmune encephalomyelitis in C57BL/6 mice.

BACKGROUND: Constipation is a common gastrointestinal dysfunction which has a potential impact on people's immune state and their quality of life. Here we investigated the effects of constipation on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). METHODS: Constipation was induced by loperamide in female C57BL/6 mice. The alternations of gut microbiota, permeability of intestinal barrier and blood-brain barrier, and histopathology of colon were assessed after constipation induction. EAE was induced in the constipation mice. Fecal microbiota transplantation (FMT) was performed from constipation mice into microbiota-depleted mice. Clinical scores, histopathology of inflammation and demyelination, Treg/Th17 and Treg17/Teff17 imbalance both in the peripheral lymphatic organs and central nervous system, cytokines include TGF-ß, GM-CSF, IL-10, IL-17A, IL-17F, IL-21, IL-22, and IL-23 in serum were assessed in different groups. RESULTS: Compared with the vehicle group, the constipation mice showed gut microbiota dysbiosis, colon inflammation and injury, and increased permeability of intestinal barrier and blood-brain barrier. We found that the clinical and pathological scores of the constipation EAE mice were severer than that of the EAE mice. Compared with the EAE mice, the constipation EAE mice showed reduced percentage of Treg and Treg17 cells, increased percentage of Th17 and Teff17 cells, and decreased ratio of Treg/Th17 and Treg17/Teff17 in the spleen, inguinal lymph nodes, brain, and spinal cord. Moreover, the serum levels of TGF-ß, IL-10, and IL-21 were decreased while the GM-CSF, IL-17A, IL-17F, IL-22, and IL-23 were increased in the constipation EAE mice. In addition, these pathological processes could be transferred via their gut microbiota. CONCLUSIONS: Our results verified that constipation induced gut microbiota dysbiosis exacerbated EAE via aggravating Treg/Th17 and Treg17/Teff17 imbalance and cytokines disturbance in C57BL/6 mice.

Automatic detection of interictal ripples on scalp EEG to evaluate the effect and prognosis of ACTH therapy in patients with infantile spasms.

OBJECTIVE: We aimed to explore the feasibility of using scalp-recorded high-frequency oscillations (HFOs) to evaluate the efficacy and prognosis of adrenocorticotropic hormone (ACTH) treatment in patients with infantile spasms. METHODS: Thirty-nine children with infantile spasms were enrolled and divided into seizure-free and non-seizure-free groups after ACTH treatment. Patients who were seizure-free were further divided into relapse and non-relapse subgroups based on the observations made during a 6-month follow-up period. Scalp ripples were detected and compared during the interictal periods before and after 2 weeks of treatment. RESULTS: After ACTH treatment, the number and channels of ripples were significantly lower, whereas the percentage decrease in the number, spectral power, and channels of ripples was significantly higher in the seizure-free group than in the non-seizure-free group. In addition, the relapse subgroup showed higher number and spectral power and wider distribution of ripples than did the non-relapse subgroup. Changes in HFOs in terms of number, spectral power, and channel of ripples were closely related to the severity of epilepsy and can indicate disease susceptibility. SIGNIFICANCE: Scalp HFOs can be used as an effective biomarker to monitor the effect and evaluate the prognosis of ACTH therapy in patients with infantile spasms.

Characterizing the seizure onset zone and epileptic network using EEG-fMRI in a rat seizure model.

Accurate epileptogenic zone (EZ) or seizure onset zone (SOZ) localization is crucial for epilepsy surgery optimization. Previous animal and human studies on epilepsy have reported that changes in blood oxygen level-dependent (BOLD) signals induced by epileptic events could be used as diagnostic markers for EZ or SOZ localization. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) recording is gaining interest as a non-invasive tool for preoperative epilepsy evaluation. However, EEG-fMRI studies have reported inconsistent and ambiguous findings. Therefore, it remains unclear whether BOLD responses can be used for accurate EZ or SOZ localization. In this study, we used simultaneous EEG-fMRI recording in a rat model of 4-aminopyridine-induced acute focal seizures to assess the spatial concordance between individual BOLD responses and the SOZ. This was to determine the optimal use of simultaneous EEG-fMRI recording in the SOZ localization. We observed a high spatial consistency between BOLD responses and the SOZ. Further, dynamic BOLD responses were consistent with the regions where the seizures were propagated. These results suggested that simultaneous EEG-fMRI recording could be used as a noninvasive clinical diagnostic technique for localizing the EZ or SOZ and could be an effective tool for mapping epileptic networks.

Enhanced ionic conductivity and lithium dendrite suppression of polymer solid electrolytes by alumina nanorods and interfacial graphite modification.

Poor room-temperature ionic conductivity and lithium dendrite formation are the main issues of solid electrolytes. In this work, rod-shaped alumina incorporation and graphite coating were simultaneously applied to poly (propylene carbonate) (PPC)-based polymer solid electrolytes (Wang et al., 2018). The obtained alumina modified solid electrolyte membrane (Al-SE) achieves a high ionic conductivity of 3.48 × 10-4 S/cm at room temperature with a wide electrochemical window of 4.6 V. The assembled NCM622/Al-SE/Li solid-state battery exhibits initial discharge capacities of 198.2 mAh/g and 177.5 mAh/g at the current density of 0.1 C and 0.5 C, with the remaining capacities of 165.8 mAh/g and 161.3 mAh/g after 100 cycles respectively. The rod-shaped structure of Al2O3 provides fast transport channels for lithium ions and its Lewis acidity promotes the dissociation of lithium salts and release of free lithium ions. The lithiophilic Al2O3 and Graphite form intimate contact with metallic Li and create fast Li+ conductive layers of Li-Al-O layer and LiC6 layer, thus facilitating the uniform deposition of Li and inhibiting Li dendrite formation during long-term cycling. This kind of composite Al-SE is expected to provide a promising alternative for practical application in solid electrolytes.

Electrical stimulation of the endopiriform nucleus attenuates epilepsy in rats by network modulation.

OBJECTIVE: Neuromodulatory anterior thalamic deep brain stimulation (DBS) is an effective therapy for intractable epilepsy, but few patients achieve complete seizure control with thalamic DBS. Other stimulation sites may be considered for anti-seizure DBS. We investigated bilateral low-frequency stimulation of the endopiriform nuclei (LFS-EPN) to control seizures induced by intracortically implanted cobalt wire in rats. METHODS: Chronic epilepsy was induced by cobalt wire implantation in the motor cortex unilaterally. Bipolar-stimulating electrodes were implanted into the EPN bilaterally. Continuous electroencephalography (EEG) was recorded using electrodes placed into bilateral motor cortex and hippocampus CA1 areas. Spontaneous seizures were monitored by long-term video-EEG, and behavioral seizures were classified based on the Racine scale. Continuous 1-Hz LFS-EPN began on the third day after electrode implantation and was controlled by a multi-channel stimulator. Stimulation continued until the rats had no seizures for three consecutive days. RESULTS: Compared with the control and sham stimulation groups, the LFS-EPN group experienced significantly fewer seizures per day and the mean Racine score of seizures was lower due to fewer generalized seizures. Ictal discharges at the epileptogenic site had significantly reduced theta band power in the LFS-EPN group compared to the other groups. INTERPRETATION: Bilateral LFS-EPN attenuates cobalt wire-induced seizures in rats by modulating epileptic networks. Reduced ictal theta power of the EEG broadband spectrum at the lesion site may be associated with the anti-epileptogenic mechanism of LFS-EPN. Bilateral EPN DBS may have therapeutic applications in human partial epilepsies.