Activates B lymphocytes and enhanced immune response: A promising adjuvant based on PLGA nanoparticle to improve the sensitivity of ZEN monoclonal antibody.

In preparing monoclonal antibodies by hybridoma cell technology, the quality of B lymphocytes used for cell fusion directly affects the sensitivity of monoclonal antibodies. To obtain B-lymphocytes producing high-quality specific antibodies for cell fusion during the immunization phase of the antigen, we prepared a TH2-Cell stimulatory delivery system as a novel adjuvant. Astragalus polysaccharide has a good ability to enhance antigenic immune response, and it was encapsulated in biocompatible materials PLGA as an immunostimulatory factor to form the delivery system (APS-PLGA). The preparation conditions of APSP were optimized using RSM to attain the highest utilization of APS. Immunization against ZEN-BSA antigen using APSP as an adjuvant to obtain B lymphocytes producing ZEN-specific antibodies for cell fusion. As results present, APSP could induce a stronger TH2 immune response through differentiating CD4 T cells and promoting IL-4 and IL-6 cytokines. Moreover, it could slow down the release efficiency of ZEN-BSA and enhance the targeting of ZEN-BSA to lymph nodes in vivo experiments. Ultimately, the sensitivity of mouse serum ZEN-specific antibodies was enhanced upon completion of immunization, indicating a significant upregulation of high-quality B lymphocyte expression. In the preparation of monoclonal antibodies, the proportion of positive wells for the first screening was 60%, and the inhibition rates of the antibodies were all similar (>50%). Then we obtained the ZEN monoclonal antibody with IC50 of 0.049 ng/mL, which was more sensitive than most antibodies prepared under conventional adjuvants. Finally, a TRFIAS strip assay was preliminarily established with a LOD value of 0.246 ng/mL.

Development of pH-freshness smart label based on gellan gum film incorporated with red cabbage anthocyanins extract and its application in postharvest mushroom.

Novel colorimetric films based on gellan gum (GG) containing red cabbage anthocyanins extract (RCAE) were prepared as pH-freshness smart labels for real-time visual detection of mushroom freshness. The GG/RCAE films had excellent pH and ammonia sensitivity. The GG/RCAE-0.2-0.3 films had the highest sensitivity to acetic acid. The SEM micrographs, AFM images, FT-IR and XRD spectra demonstrated that RCAE were successfully combined into the film-forming substrate. The incorporation of RCAE resulted in the increase of thermal stability, opacity and surface hydrophobicity of films. Meanwhile, the GG/RCAE-0.2 film exhibited stronger tensile strength and excellent color stability at 4℃. The color changes of GG/RCAE-0.2 film were visually easier to distinguish during the storage of mushroom. The results showed the GG/RCAE films could be used as pH-freshness smart labels to detect the freshness of fruits and vegetables.

Dexmedetomidine protects against sepsis-induced lung injury through autophagy and Smad2/3 signaling pathway.

Objectives: Dexmedetomidine (Dex) is a potent α2-adrenergic receptor(α2-AR) agonist that has been shown to protect against sepsis-induced lung injury, however, the underlying mechanisms of this protection are not fully understood. Autophagy and the Smad2/3 signaling pathway play important roles in sepsis-induced lung injury, but the relationship between Dex and Smad2/3 is not clear. This study aimed to investigate the role of autophagy and the Smad2/3 signaling pathway in Dex-mediated treatment of sepsis-induced lung injury. Sepsis was performed using cecal ligation and puncture (CLP) in C57BL/6J mice. Materials and Methods: Mice were randomly assigned to four groups (n=6 per group): sham, CLP, CLP-Dex, and CLP-Dex-YOH, Yohimbine hydrochloride (YOH) is an α2-AR blocker. The cecum was carefully separated to avoid blood vessel damage and was identified and punctured twice with an 18-gauge needle. The pathological changes, inflammatory factor levels, oxidative stress, autophagy, Smad2/3 signaling pathway-related protein levels in lung tissues, and the activity of superoxide dismutase (SOD) and malonaldehyde (MDA) in the serum were measured. Results: CLP-induced lung injury was reflected by increased levels of inflammatory cytokines, apoptosis, and oxidative stress, along with an increase in the expression of autophagy and Smad2/3 signaling pathway-related proteins. Dex could reverse these changes and confer a protective effect on the lung during sepsis. However, the administration of YOH significantly reduced the positive effects of Dex in mice with sepsis. Conclusion: Dex exerts its beneficial effects against sepsis-induced lung injury through the regulation of autophagy and the Smad2/3 signaling pathway.

Data-Driven Based Characterization of Anisotropic Mechanical Properties for Cancellous Bone From Low-Resolution CT Images.

OBJECTIVES: Exploring the anisotropic mechanical behavior of cancellous bone is crucial for in-vivo bone biomechanical analysis. However, it is challenging to characterize anisotropic mechanical behaviors under low-resolution (LR) clinical CT images due to a lack of microstructural information. The data-driven method proposed in this article accurately characterizes the anisotropic mechanical properties of cancellous bone from LR clinical CT images. METHODS: The trabecular bone cubes of sheep are used to obtain a high-resolution (HR) micro-CT and an LR clinical CT image dataset. First, an auto-encoder model is trained using HR image data. Microstructural features are extracted by the encoder. A fast super-resolution (FSR) model is trained to map LR bone cubes to the features extracted from corresponding HR samples. The pretrained FSR model is used to convert LR clinical CT images to encoded microstructural features. The features are later used to predict target histomorphological parameters, anisotropic elastic tensors, and fabric tensors based on a fully connected neural network. RESULTS: The data-driven model accurately predicts the elastic tensor and fabric tensor of trabecular bones with LR CT images with 0.6 mm/pixel spatial resolution. It was verified that LR clinical CT images could generate microstructural information using a generative deep-learning model and an up-sampling operation. SIGNIFICANCE: This study proves that clinical medical images of cancellous bone can be used for analysis of complex mechanical properties using a data-driven method, which is useful for real-time bone defect diagnosis and personalized bone prosthesis design in clinical application.

The relationship between gut microbiota and insomnia: a bi-directional two-sample Mendelian randomization research.

Introduction: Insomnia is the second most common mental health issue, also is a social and financial burden. Insomnia affects the balance between sleep, the immune system, and the central nervous system, which may raise the risk of different systemic disorders. The gut microbiota, referred to as the "second genome," has the ability to control host homeostasis. It has been discovered that disruption of the gut-brain axis is linked to insomnia. Methods: In this study, we conducted MR analysis between large-scale GWAS data of GMs and insomnia to uncover potential associations. Results: Ten GM taxa were detected to have causal associations with insomnia. Among them, class Negativicutes, genus Clostridiuminnocuumgroup, genus Dorea, genus Lachnoclostridium, genus Prevotella7, and order Selenomonadalesare were linked to a higher risk of insomnia. In reverse MR analysis, we discovered a causal link between insomnia and six other GM taxa. Conclusion: It suggested that the relationship between insomnia and intestinal flora was convoluted. Our findings may offer beneficial biomarkers for disease development and prospective candidate treatment targets for insomnia.

Quercetin, Main Active Ingredient of Moutan Cortex, Alleviates Chronic Orofacial Pain via Block of Voltage-Gated Sodium Channel.

BACKGROUND: Chronic orofacial pain (COP) therapy is challenging, as current medical treatments are extremely lacking. Moutan Cortex (MC) is a traditional Chinese medicine herb widely used for chronic inflammatory diseases. However, the mechanism behind MC in COP therapy has not been well-established. The purpose of this study was to identify the active ingredients of MC and their specific underlying mechanisms in COP treatment. METHODS: In this study, the main active ingredients and compound-target network of MC in COP therapy were identified through network pharmacology and bioinformatics analysis. Adult male Sprague-Dawley rats received oral mucosa lipopolysaccharide (LPS) injection to induce COP. Pain behaviors were evaluated by orofacial mechanical nociceptive assessment after intraganglionar injection. In vitro inflammatory cytokines in LPS-pretreated human periodontal ligament stem cells (hPDLSCs) and rat primary cultural trigeminal ganglion (TG) neurons were quantified by real-time quantitative polymerase chain reaction (RT-qPCR). Schrödinger software was used to verify the molecular docking of quercetin and critical targets. Whole-cell recording electrophysiology was used to evaluate the effect of quercetin on voltage-gated sodium (Na v ) channel in rat TG neurons. RESULTS: The assembled compound-target network consisted of 4 compounds and 46 targets. As 1 of the active components of MC correlated with most related targets, quercetin alleviated mechanical allodynia in LPS-induced rat model of COP (mechanical allodynia threshold median [interquartile range (IQR) 0.5 hours after drug administration: vehicle 1.3 [0.6-2.0] g vs quercetin 7.0 [6.0-8.5] g, P = .002). Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that immune response and membrane functions play essential roles in MC-COP therapy. Five of the related targets were identified as core targets by protein-protein interaction analysis. Quercetin exerted an analgesic effect, possibly through blocking Na v channel in TG sensory neurons (peak current density median [IQR]: LPS -850.2 [-983.6 to -660.7] mV vs LPS + quercetin -589.6 [-711.0 to -147.8] mV, P = .006) while downregulating the expression level of proinflammatory cytokines-FOS (normalized messenger RNA [mRNA] level mean ± standard error of mean [SEM]: LPS [2. 22 ± 0.33] vs LPS + quercetin [1. 33 ± 0.14], P = .034) and TNF-α (normalized mRNA level mean ± SEM: LPS [8. 93 ± 0.78] vs LPS + quercetin [3. 77 ± 0.49], P < .0001). CONCLUSIONS: Identifying Na v as the molecular target of quercetin clarifies the analgesic mechanism of MC, and provides ideas for the development of novel selective and efficient chronic pain relievers.

Preparation, characterization and application of pH-responsive smart film based on chitosan/zein and red radish anthocyanin.

This research was aimed at developing a novel pH-responsive smart film made of chitosan, zein and red radish anthocyanin (RRA). The morphology, interaction, crystallization, thermal stability, physiochemical properties and pH sensitivity of films were analyzed. The smart film was applied to monitor the freshness of mushroom (Agaricus bisporus). The results of morphology (SEM) and spectrum (FT-IR and XRD) indicated that the incorporation of RRA could enhance the interaction between polymer matrix. The addition of RRA had no significant effect on the thermal stability of films. The chitosan/zein/red radish anthocyanin (C/Z/R) films exhibited higher tensile strength, Young's modulus, hydrophobicity, antioxidant activity and lower elongation at break. The C/Z/R films had stronger water vapor and gas barrier capacity. The C/Z/R films showed a pH-sensitive color variation from red (pH 2) to green (pH 12) and good reversibility under alkaline and acidic environment. The prepared smart film could be successfully used for the quality monitoring of mushroom.

A Bayesian method with nonlinear noise model to calibrate constitutive parameters of soft tissue.

The measured mechanical responses of soft tissue exhibit large variability and errors, especially for the softest brain tissue, while calibrating its constitutive parameters in a deterministic way remains a common practice. Here we implement a Bayesian method considering the nonlinear noise model to calibrate constitutive parameters of brain tissue. A probability model is first developed based on the measured experimental data, likelihood function, and prior function, from which the posterior distributions of model parameters are formulated. The likelihood function considers the nonlinear behaviors of the constitutive response and noise distribution of the experimentally measured data. Meanwhile, the prior predictive distribution is computed to check the probability model preliminarily. Secondly, the Markov Chain Monte Carlo (MCMC) method is used to compute the posterior distributions of model parameters, enabling assessment of parameter uncertainty, correlation, and model calibration error. Finally, the posterior predictive distributions of the overall response, constitutive response, and noise response are computed to validate the probabilistic model, all of which are consistent with the corresponding data. Furthermore, the effect of the prior distribution, experimental data, and noise model on posterior distribution is studied. Our study provides a general approach to calibrating constitutive parameters of soft tissue despite errors and large variability in experimental data.

Mechanical mechanism and indicator of diffuse axonal injury under blast-type acceleration.

Diffuse axonal injury (DAI) caused by acceleration is one of the most prominent forms of blast-induced Traumatic Brain Injury. However, the mechanical mechanism and indicator of axonal deformation-induced injury under blast-type acceleration with high peak and short duration are unclear. This study constructed a multilayer head model that can reflect the response characteristics of translational and rotational acceleration (the peak time of which is within 0.5 ms). Based on von Mises stress, axonal strain and axonal strain rate indicators, the physical process of axonal injury is studied, and the vulnerable area under blast-type acceleration load is given. In the short term (within 1.75 ms), dominated by sagittal rotational acceleration peaks, the constraint of falx and tentorium rapidly imposes the inertial load on the brain tissue, resulting in a high-rate deformation of axons (axonal strain rate of which exceed 100 s-1). For a long term (after 1.75 ms), fixed-point rotation of the brain following the head causes excessive distortion of brain tissue (von Mises stress of which exceeds 15 kPa), resulting in a large axonal stretch strain where the main axonal orientation coincides with the principal strain direction. It is found that the axonal strain rate can better indicate the pathological axonal injury area and coincides with external inertial loading in the risk areas, which suggests that DAI under blast-type acceleration overload is mainly caused by the rapid axonal deformation instead of by the excessive axonal strain. The research in this paper helps understand and diagnose blast-induced DAI.

Bacterial community dynamics and metabolic functions prediction in white button mushroom (Agaricus bisporus) during storage.

White button mushroom (Agaricus bisporus) is rich in nutritional value, but it is easily infected by microorganisms during storage, which leads to spoilage and shortens the storage time. In this paper, A. bisporus at different storage times was sequenced by Illumina Novaseq 6000 platform. QIIME2 and PICRUSt2 were used to analyze the changes of bacterial community diversity and predict metabolic functions during storage of A. bisporus. Then, the pathogenic bacteria were isolated and identified from the spoilt samples of A. bisporus with black spot. The results showed that the bacterial species richness of A. bisporus surface gradually decreased. 2,291 ASVs were finally obtained through DADA2 denoising, belonging to 27 phyla, 60 classes, 154 orders, 255 families and 484 genera. The abundance of Pseudomonas on the surface of fresh A. bisporus sample was 22.8%, which increased to 68.7% after 6 days of storage. The abundance significantly increased and became a dominant spoilage bacterium. In addition, A total of 46 secondary metabolic pathways belonging to 6 categories of primary biological metabolic pathways were predicted during storage of A. bisporus, and metabolism (71.8%) was the main functional pathway. Co-occurrence network analysis revealed that the dominant bacterium Pseudomonas was positively correlated with 13 functional pathways (level 3). A total of 5 strains were isolated and purified from diseased A. bisporus surface. The test of pathogenicity showed that Pseudomonas tolaasii caused serious spoilage of A. bisporus. The study provided a theoretical basis for the development of antibacterial materials to reduce related diseases and prolong the storage time of A. bisporus.

Upregulations of high mobility group box 1 and TLR4/NF-κB signaling pathway in hippocampus and serum of rats with febrile seizure.

PURPOSE: The aim of this study was to explore the alternations regarding the HMGB1 and TLR4/NF-κB signaling pathway in juvenile rats with febrile seizure (FS). MATERIALS AND METHODS: During the animal modeling of the FS, seizures were triggered every four days by hot water (45 °C), and repeated ten times. After forty days' modeling, rats were divided into different groups according to the degree of seizure (FS (0) - FS (V)). Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the mRNA expressions of the HMGB1, TLR4 and NF-κB in the hippocampus, while Western-blot (WB) and immunofluorescence (IF) were employed to assess protein expressions. The enzyme-linked immunosorbent assay (ELISA) was used for analyzing the protein expressions in peripheral blood. RESULTS: The mRNA levels of the HMGB1, TLR4 and NF-κB in the hippocampus of both FS (V) and FS (IV) groups were significantly higher than WT, while there was no difference between FS (III) and WT. Concerning protein expressions, increased levels of the HMGB1, TLR4, and NF-κB in FS (V) were observed with a good consistency between the WB and IF, while no significant upregulation was shown in FS (IV). The ELISA results showed that the significance of the augmented proteins between the FS (V) and WT were smaller in the serum than the hippocampus. CONCLUSIONS: Our study shows seizure degree-related upregulations of HMGB1 and TLR4/NF-κB signaling pathway both in hippocampus and serum of juvenile rats with FS, suggesting the involvement of TLR/NF-κB pathway in inflammation promoted by HMGB1 during FS.

Origins of brain tissue elasticity under multiple loading modes by analyzing the microstructure-based models.

Constitutive behaviors and material properties of brain tissue play an essential role in accurately modeling its mechanical responses. However, the measured mechanical behaviors of brain tissue exhibit a large variability, and the reported elastic modulus can differ by orders of magnitude. Here we develop the micromechanical models based on the actual microstructure of the longitudinally anisotropic plane of brain tissue to investigate the microstructural origins of the large variability. Specifically, axonal fiber bundles with the specified configurations are distributed in an equivalent matrix. All micromechanical models are subjected to multiple loading modes, such as tensile, compressive, and shear loading, under periodic boundary conditions. The predicted results agree well with the experimental results. Furthermore, we investigate how brain tissue elasticity varies with its microstructural features. It is revealed that the large variability in brain tissue elasticity stems from the volume fraction of axonal fiber, the aspect ratio of axonal fiber, and the distribution of axonal fiber orientation. The volume fraction has the greatest impact on the mechanical behaviors of brain tissue, followed by the distribution of axonal fiber orientation, then the aspect ratio. This study provides critical insights for understanding the microstructural origins of the large variability in brain tissue elasticity.

Finite element analysis of conductive hearing loss caused by fixation and detachment of ligament and tendon in the middle ear.

BACKGROUND AND OBJECTIVE: The fixation of ligament and tendon of the middle ear often occurs after chronic otitis media surgery. However, there are relatively few studies on the effect of ligament and tendon on sound transmission in the human middle ear. Here, the finite element model and lumped parameter model are used to study the effect of ligament and tendon fixation and detachment on sound transmission in human ear. METHODS: In this paper, the finite element model including the external auditory canal, middle ear and simplified inner ear is used to calculate and compare the middle ear frequency response of the normal and tympanosclerosis under pure tone stimulation. In addition, the lumped parametric model is taken into account to illustrate the effect of ligament and tendon stiffness on the human ear transmission system. RESULTS: The results indicate that the motion of the tympanic membrane and stapes is reduced by ligament and tendon fixation. Although ligament and tendon detachment have a limited effect in the piston-motion direction, the stability of motion in the plane perpendicular to the piston-motion direction is significantly reduced. Most significantly, the ligament and tendon fixation cause a hearing effect of about 18 dB, which is greater in the plane perpendicular to the piston-motion direction after ligament and tendon detachment than in the piston-motion direction. CONCLUSIONS: In this study, the calculation accuracy of the lumped parameter and the finite element model is studied, and the effect of ligament and tendon on hearing loss is further explored through the finite element model with high calculation accuracy, which is helpful to understand the role of ligament and tendon in the sound transmission mechanism of the human middle ear. The study of ligament and tendon on conductive hearing loss provides a reference for clinical treatment of tympanosclerosis.

Case report: A novel STXBP1 splice variant and the landscape of splicing-involved STXBP1-related disorders.

STXBP1 variants are one of the most common genetic causes of neurodevelopmental disorders and epilepsy, wherein STXBP1-related disorders are characterized by neurodevelopmental abnormalities in 95% and seizures in 89% of affected patients. However, the spectrums of both genotype and phenotype are quite wide and diverse, with a high baseline variability even for recurrent STXBP1 variants. Until now, no clear genotype-phenotype correlations have been established and multiple disease mechanisms have been proposed for STXBP1-related disorders. Without an ascertained disease cause for many cases of STXBP1 variants, it is challenging to manage this disease in an effective manner and current symptom-based treatments are focused on seizure control only, which has a minimal impact on global development. A novel STXBP1 canonical splice variant, NM_001032221.4:c.578+2T>C, was reported in this study, together with detailed documentation of disease manifestations and treatment management. Further RNA expression analysis revealed abnormal intron retention and possible production of truncated STXBP1 proteins as a likely pathogenic mechanism. More importantly, the landscape of previously understudied STXBP1 splice variants and functional investigations was assessed for the first time to provide a context for the discussion of the complicated genotype-phenotype relationship of STXBP1-related disorders. Future cases of this disorder and a deeper mechanism-based understanding of its pathogenic cause are required for precision medicine and better disease management.

Characterization of middle ear soft tissue damping and its role in sound transmission.

Damping plays an important role in the middle ear (ME) sound transmission system. However, how to mechanically characterize the damping of ME soft tissues and the role of damping in ME sound transmission have not yet reached a consensus. In this paper, a finite element (FE) model of the partial external and ME of the human ear, considering both Rayleigh damping and viscoelastic damping for different soft tissues, is developed to quantitatively investigate the damping in soft tissues effects on the wide-frequency response of the ME sound transmission system. The model-derived results can capture the high-frequency (above 2 kHz) fluctuations and obtain the 0.9 kHz resonant frequency (RF) of the stapes velocity transfer function (SVTF) response. The results show that the damping of pars tensa (PT), stapedial annular ligament (SAL) and incudostapedial joints (ISJ) can help smooth the broadband response of the umbo and stapes footplate (SFP). It is found that, between 1 and 8 kHz, the damping of the PT increases the magnitude and phase delay of the SVTF above 2 kHz while the damping of the ISJ can avoid excessive phase delay of the SVTF, which is important in maintaining the synchronization in high-frequency vibration but has not been revealed before. Below 1 kHz, the damping of the SAL plays a more important role, and it can decrease the magnitude but increases the phase delay of the SVTF. This study has implications for a better understanding of the mechanism of ME sound transmission.

Experimentally characterizing the spatially varying anisotropic mechanical property of cancellous bone via a Bayesian calibration method.

Traditional experimental tests for characterizing bone's mechanical properties usually hypothesize a uniaxial stress condition without quantitatively evaluating the influence of spatially varying principal material orientations, which cannot accurately predict the mechanical properties distribution of bones in vivo environment. In this study, a Bayesian calibrating procedure was developed using quantified multiaxial stress to investigate cancellous bone's local anisotropic elastic performance around joints as the spatial variation of main bearing orientations. First, the bone cube specimens from the distal femur of sheep are prepared using traditional anatomical axes. The multiaxial stress state of each bone specimen is calibrated using the actual principal material orientations derived from fabric tensor at different anatomical locations. Based on the calibrated multiaxial stress state, the process of identifying mechanical properties is described as an inverse problem. Then, a Bayesian calibration procedure based on a surrogate constitutive model was developed via multiaxial stress correction to identify the anisotropic material parameters. Finally, a comparison between the experiment and simulation results is discussed by applying the optimal model parameters obtained from the Bayesian probability distribution. Compared to traditional uniaxial methods, our results prove that the calibration based on the spatial variation of the main bearing orientations can significantly improve the accuracy of characterizing regional anisotropic mechanical responses. Moreover, we determine that the actual mechanical property distribution is influenced by complicated mechanical stimulation. This study provides a novel method to evaluate the spatially varying mechanical properties of bone tissues enduring complex mechanical loading accurately and effectively. It is expected to provide more realistic mechanical design targets in vivo for a personalized artificial bone prosthesis in clinical treatment.

Changes of serum metabolomics and gut microbiota reveal specific characteristics of children with febrile seizures.

BACKGROUND AND PURPOSE: Febrile seizures (FS) pose a severe threat to the neurological development of children. Probing the abnormality of host metabolism is essential for the prevention, diagnosis, and treatment of FS. METHODS: Based on clinically collected serum and fecal samples, we used nontargeted metabolomics and 16S rDNA sequencing to explore the relationship of serum metabolite levels and gut microbiota community with the occurrence of FS. RESULTS: Metabolomic analysis revealed abnormalities in multiple metabolic pathways in serum of FS patients, such as tryptophan metabolism and steroid hormone biosynthesis. Intestinal flora analysis indicated that the α-diversity of gut microbiota in FS patients was significantly reduced. In addition, the relative abundance of a variety of bacteria at the phylum level was remarkably changed in patients with FS, including decreased Firmicutes and Verrucomicrobia. Eleven serum metabolites were identified to be biomarker candidates for FS diagnosis. With the help of a panel biomarker strategy combining four biomarkers as a cluster, four bacteria (i.e., Rothia, Coprococcus, Lactobacillus, and Oscillospira) in a defined panel displayed perfect differentiation of subtypes of FS. CONCLUSIONS: Combining metabolomic and intestinal flora analysis revealed specific characteristics of children with FS, and provided new clues for the diagnosis of FS and the classification of seizure types. In summary, these findings may provide new insights into revealing the significance of serum metabolites and gut microbiota in the pathogenesis of FS.

Isolation of Bacteria Aptamers with Non-SELEX for the Development of a Highly Sensitive Colorimetric Assay Based on Dual Signal Amplification.

In this work, an aptamer against Escherichia coli is isolated via non-SELEX, which executes efficient selection by employing repetitive cycles of centrifugation-based partitioning, and the binding site of the aptamer on E. coli cell surfaces is inferred to be a membrane protein. Moreover, truncated sequence 2-17-2 with a higher affinity (Kd = 101.76 nM) is employed for highly sensitive colorimetric detection of bacteria based on the dual signal amplification strategy. When targets exist, the release of DNA 1 from the polymer activates a hybridization chain reaction (HCR) between DNA 1 and DNA 2, thereby inducing the aggregation of probe 1. Subsequently, DNA 3 dissociated from probe 1 as a linker DNA further assembles probe 2/3. In this system, two types of DNA@gold nanoparticles (AuNPs) coexist and successively aggregate AuNPs based on divergent triggering mechanisms. Under optimal conditions, the dual signal amplification strategy presents excellent sensitivity (10 CFU mL-1) and specificity, as well as the realization of real sample analysis.

Epidermal nevus syndrome with the mutation of PTCH1 gene and cerebral infarction: a case report and review of the literature.

BACKGROUND: Epidermal nevus syndrome is a group of congenital neuroectodermal and/or mesodermal disorders characterized by the epidermal nevi in common association with cerebral, eye, skeletal, cardiovascular, and renal abnormalities. Epidermal nevus syndrome is a rare syndrome, and epidermal nevus syndrome with the mutation of PTCH1 gene and cerebral infarction is even rarer and has not been reported to the best of our knowledge. CASE PRESENTATION: We report the case of a 10-month-old Chinese female patient who presented to our pediatric neurologic department, University of Wenzhou medical teaching Hospital, Hangzhou. She has mobility disorders on the right limbs and recurrent seizures. She had congenital disorder accompanied by brownish-black and verrucose plaques on the right side of the face as well as extensive brownish-black plaques and brown nevi on the right side of the trunk and the right arm. Epidermal nevus syndrome was diagnosed on the basis of her symptoms. Somatic sebaceous nevi and hypoplastic defects of skin, cerebra, eyes, skeleton, and cardiovascular and renal system were observed. However, in addition to the typical clinical characteristics, the patient also has a mutation (c.109G > T) in PTCH1 gene and cerebral infarction. We present a novel case report and literature review. CONCLUSION: To our knowledge, epidermal nevus syndrome with a mutation of PTCH1 gene and cerebral infarction has not been reported previously. This case report may contribute to characterizing the phenotype of epidermal nevus syndrome, help clinicians be aware of the association of this condition with PTCH1 gene and cerebral infarction, raise clinical suspicion, and improve early therapy.

Revealing the Effect of Skull Deformation on Intracranial Pressure Variation During the Direct Interaction Between Blast Wave and Surrogate Head.

Intracranial pressure (ICP) during the interaction between blast wave and the head is a crucial evaluation criterion for blast-induced traumatic brain injury (bTBI). ICP variation is mainly induced by the blast wave transmission and skull deformation. However, how the skull deformation influences the ICP remains unclear, which is meaningful for mitigating bTBI. In this study, both experimental and numerical models are developed to elucidate the effect of skull deformation on ICP variation. Firstly, we performed the shock tube experiment of the high-fidelity surrogate head to measure the ICP, the blast overpressure, and the skull surface strain of specific positions. The results show that the ICP profiles of all measured points show oscillations with positive and negative change, and the variation is consistent with the skull surface strain. Further numerical analysis reveals that when the blast wave reaches the measured point, the peak overpressure transmits directly through the skull to the brain, forming the local positive ICP peak, and the impulse induces the local inward deformation of the skull. As the peak overpressure passes through, the blast impulse impacts the nearby skull supported by the soft and incompressible brain tissue and extrudes the skull outward in the initial position. The inward and outward skull deformation leads to the oscillation of ICP. These numerical analyses agree with experimental results, which explain the appearance of negative and positive ICP peaks and the synchronization of negative ICP with surface strain. The study has implications for medical injury diagnosis and protective equipment design.