High-resolution myelin-water fraction and quantitative relaxation mapping using 3D ViSTa-MR fingerprinting.

PURPOSE: This study aims to develop a high-resolution whole-brain multi-parametric quantitative MRI approach for simultaneous mapping of myelin-water fraction (MWF), T1, T2, and proton-density (PD), all within a clinically feasible scan time. METHODS: We developed 3D visualization of short transverse relaxation time component (ViSTa)-MRF, which combined ViSTa technique with MR fingerprinting (MRF), to achieve high-fidelity whole-brain MWF and T1/T2/PD mapping on a clinical 3T scanner. To achieve fast acquisition and memory-efficient reconstruction, the ViSTa-MRF sequence leverages an optimized 3D tiny-golden-angle-shuffling spiral-projection acquisition and joint spatial-temporal subspace reconstruction with optimized preconditioning algorithm. With the proposed ViSTa-MRF approach, high-fidelity direct MWF mapping was achieved without a need for multicompartment fitting that could introduce bias and/or noise from additional assumptions or priors. RESULTS: The in vivo results demonstrate the effectiveness of the proposed acquisition and reconstruction framework to provide fast multi-parametric mapping with high SNR and good quality. The in vivo results of 1 mm- and 0.66 mm-isotropic resolution datasets indicate that the MWF values measured by the proposed method are consistent with standard ViSTa results that are 30× slower with lower SNR. Furthermore, we applied the proposed method to enable 5-min whole-brain 1 mm-iso assessment of MWF and T1/T2/PD mappings for infant brain development and for post-mortem brain samples. CONCLUSIONS: In this work, we have developed a 3D ViSTa-MRF technique that enables the acquisition of whole-brain MWF, quantitative T1, T2, and PD maps at 1 and 0.66 mm isotropic resolution in 5 and 15 min, respectively. This advancement allows for quantitative investigations of myelination changes in the brain.

Coarse-to-Fine(r) Automatic Familiar Face Recognition in the Human Brain.

At what level of spatial resolution can the human brain recognize a familiar face in a crowd of strangers? Does it depend on whether one approaches or rather moves back from the crowd? To answer these questions, 16 observers viewed different unsegmented images of unfamiliar faces alternating at 6 Hz, with spatial frequency (SF) content progressively increasing (i.e., coarse-to-fine) or decreasing (fine-to-coarse) in different sequences. Variable natural images of celebrity faces every sixth stimulus generated an objective neural index of single-glanced automatic familiar face recognition (FFR) at 1 Hz in participants' electroencephalogram (EEG). For blurry images increasing in spatial resolution, the neural FFR response over occipitotemporal regions emerged abruptly with additional cues at about 6.3-8.7 cycles/head width, immediately reaching amplitude saturation. When the same images progressively decreased in resolution, the FFR response disappeared already below 12 cycles/head width, thus providing no support for a predictive coding hypothesis. Overall, these observations indicate that rapid automatic recognition of heterogenous natural views of familiar faces is achieved from coarser visual inputs than generally thought, and support a coarse-to-fine FFR dynamics in the human brain.

Intracerebral electrical stimulation of the right anterior fusiform gyrus impairs human face identity recognition.

Brain regions located between the right fusiform face area (FFA) in the middle fusiform gyrus and the temporal pole may play a critical role in human face identity recognition but their investigation is limited by a large signal drop-out in functional magnetic resonance imaging (fMRI). Here we report an original case who is suddenly unable to recognize the identity of faces when electrically stimulated on a focal location inside this intermediate region of the right anterior fusiform gyrus. The reliable transient identity recognition deficit occurs without any change of percept, even during nonverbal face tasks (i.e., pointing out the famous face picture among three options; matching pictures of unfamiliar or familiar faces for their identities), and without difficulty at recognizing visual objects or famous written names. The effective contact is associated with the largest frequency-tagged electrophysiological signals of face-selectivity and of familiar and unfamiliar face identity recognition. This extensive multimodal investigation points to the right anterior fusiform gyrus as a critical hub of the human cortical face network, between posterior ventral occipito-temporal face-selective regions directly connected to low-level visual cortex, the medial temporal lobe involved in generic memory encoding, and ventral anterior temporal lobe regions holding semantic associations to people's identity.

Knockdown of Foxg1 in supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse cochlea.

Foxg1 is one of the forkhead box genes that are involved in morphogenesis, cell fate determination, and proliferation, and Foxg1 was previously reported to be required for morphogenesis of the mammalian inner ear. However, Foxg1 knock-out mice die at birth, and thus the role of Foxg1 in regulating hair cell (HC) regeneration after birth remains unclear. Here we used Sox2CreER/+ Foxg1loxp/loxp mice and Lgr5-EGFPCreER/+ Foxg1loxp/loxp mice to conditionally knock down Foxg1 specifically in Sox2+ SCs and Lgr5+ progenitors, respectively, in neonatal mice. We found that Foxg1 conditional knockdown (cKD) in Sox2+ SCs and Lgr5+ progenitors at postnatal day (P)1 both led to large numbers of extra HCs, especially extra inner HCs (IHCs) at P7, and these extra IHCs with normal hair bundles and synapses could survive at least to P30. The EdU assay failed to detect any EdU+ SCs, while the SC number was significantly decreased in Foxg1 cKD mice, and lineage tracing data showed that much more tdTomato+ HCs originated from Sox2+ SCs in Foxg1 cKD mice compared to the control mice. Moreover, the sphere-forming assay showed that Foxg1 cKD in Lgr5+ progenitors did not significantly change their sphere-forming ability. All these results suggest that Foxg1 cKD promotes HC regeneration and leads to large numbers of extra HCs probably by inducing direct trans-differentiation of SCs and progenitors to HCs. Real-time qPCR showed that cell cycle and Notch signaling pathways were significantly down-regulated in Foxg1 cKD mice cochlear SCs. Together, this study provides new evidence for the role of Foxg1 in regulating HC regeneration from SCs and progenitors in the neonatal mouse cochlea.

Potential Application of Electrical Stimulation in Stem Cell-Based Treatment against Hearing Loss.

Deafness is a common human disease, which is mainly caused by irreversible damage to hair cells and spiral ganglion neurons (SGNs) in the mammalian cochlea. At present, replacement of damaged or missing hair cells and SGNs by stem cell transplantation therapy is an effective treatment. However, the survival rate of stem cell transplantation is low, with uncontrollable differentiation hindering its application. Most researchers have focused on biochemical factors to regulate the growth and differentiation of stem cells, whereas little study has been performed using physical factors. This review intends to illustrate the current problems in stem cell-based treatment against deafness and to introduce electric field stimulation as a physical factor to regulate stem cell behavior and facilitate stem cell therapy to treat hearing loss in the future.

Spectral Analysis of Interaction between Human Telomeric G-Quadruplex and Liliflorin A, the First Lignan Derivative Interacted with G-Quadruplex DNA.

Human telomeric G-quadruplex is a four-stranded structure folded by guanines (G) via Hoogsteen hydrogen bonding. The ligands which stabilize the G-quadruplex are often telomerase inhibitors and may become antitumor agents. Here, the interaction between a lignan derivative liliflorin A and human telomeric sequence dGGG (TTAGGG)3G-quadruplex HTG21 were examined by CD, FRET, and NMR spectroscopic methods. In addition, Molecular Docking was used to study the binding of liliflorin A to dTAGGG (TTAGGG)3 G-quadruplex HTG23. The CD data showed that liliflorin A enhanced HTG21 T(m). The T(m) value of G-quadruplex was enhanced 3.2 degrees C by 4.0 µmol x L(-1) liliflorin A in FRET. The NMR spectra of HTG21 showed vivid alteration after reacting with liliflorin A in 3 hours. Molecular Docking suggested liliflorin A bound to the wide groove of HTG23 at G9, G10, G16 and G17. Liliflorin A was the first lignan derivative that could stabilize HTG21 selectively and provided a new candidate for antitumor drug design targeting on human telomeric G-quadruplex.

[Correlation study between lupus nephritis patients of rheumatism syndrome and SLEDAI--a clinical study].

OBJECTIVE: To explore lupus nephritis (LN) patients' monocyte chemotactic protein 1 (MCP-1) and urinary IP-10 (ulP-10) levels, the correlation between each clinical activity index and rheumatism syndrome, thereby proving objective evidence for microscopic typing of rheumatism syndrome. METHODS: Totally 60 LN patients were assigned to the rheumatism group (31 cases) and the non-rheumatism group (29 cases). Besides, 20 healthy volunteers were recruited as the normal control group. Clinical data and renal pathology were collected, and urinary levels of MCP-1 and IP-10 detected by ELISA. The correlation between rheumatism syndrome and each activity index as well as manifestations of clinical activities was comprehensively analyzed. Results (1) Patients in the rheumatism group were more liable to occur fever, serositis, edema, and hypertension (P<0.05). (2) Compared with the non-rheumatism group, patients in the rheumatism group exhibited much higher levels of 24 h protein quantification and blood urea nitrogen, higher levels of uMCP-1 and ulP-10. Microscopic hematuria, anti-ds-DNA, anti-Sm, the positive rate of AnuA, scores of SLEDAI and BILAG were higher in the rheumatism group than in the non-rheumatism group (P<0.05). Levels of plasma albumin and complement C3 were lower in the rheumatism group than in the non-rheumatism group (P<0.05). (3) The average activity index (AI) of the renal pathology was higher in the rheumatism group than in the non-rheumatism group. The most frequent pathological type of rheumatism group was type IV of LN. CONCLUSIONS: More severe renal damage and immune abnormality occurred in LN patients of rheumatism syndrome. Rheumatism syndrome is closely correlated to clinical activity indices.

Template-independent, in situ grown DNA nanotail enabling label-free femtomolar chronocoulometric detection of nucleic acids.

A routine electrochemical DNA (E-DNA) sensor requires either an exquisite design of conformation-switchable recognition probe that is critical to facilitate electron transfer at a sensing interface, or a template-dependent DNA amplification, which often involves designing prone-to-false "sticky ends" and labeling redox tags at one end of the signal probes. Here we report an in situ grown DNA nanotail (IGT)-mediated straightforward and template-free signal amplification strategy for highly sensitive and sequence-specific DNA detection. This novel electrochemical IGT (E-IGT) DNA sensor can quantify target nucleic acids in a label-free manner because the electrochemical signals are generated by chronocoulometric interrogation of redox [Ru(NH3)6](3+) that electrostatically and quantitatively binds to the negatively charged phosphate moieties in the electrode surface-attached DNA. By introduction of terminal deoxynucleoside transferase (TdT) to this sensor design, both the sensitivity and selectivity have been significantly enhanced. This DNA sensor achieves an impressive detection limit of 20 fM for a DNA sequence with 22 nucleotides, which is lower than that of an analogous optical DNA sensor by 2 orders of magnitude. More importantly, it exhibits excellent selectivity against even a single-base mismatched sequence. In addition, this novel DNA sensor presents reliable reusability and is capable of measuring target DNA in complex matrixes, such as undiluted human serum, with minimal interference. These advantages make our E-IGT sensor a promising contender in the E-DNA sensor family for medical diagnostics.

Brain-Derived Exosomal miRNA Profiles upon Experimental SAE Rats and Their Comparison with Peripheral Exosomes.

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction secondary to body infection without overt central nervous system infection. Dysregulation of miRNA expression in the transcriptome can spread through RNA transfer in exosomes, providing an early signal of impending neuropathological changes in the brain. Here, we comprehensively analyzed brain-derived exosomal miRNA profiles in SAE rats (n = 3) and controls (n = 3). We further verified the differential expression and correlation of brain tissue, cerebrospinal fluid, and plasma exosomal miRNAs in SAE rats. High-throughput sequencing of brain-derived exosomal miRNAs identified 101 differentially expressed miRNAs, of which 16 were downregulated and 85 were upregulated. Four exosomal miRNAs (miR-127-3p, miR-423-3p, mR-378b, and miR-106-3p) were differentially expressed and correlated in the brain tissue, cerebrospinal fluid, and plasma, revealing the potential use of miRNAs as SAE liquid brain biopsies. Understanding exosomal miRNA profiles in SAE brain tissue and exploring the correlation with peripheral exosomal miRNA can contribute to a comprehensive understanding of miRNA changes in the SAE pathological process and provide the possibility of establishing early diagnostic assays.

A neural marker of the human face identity familiarity effect.

Human adults associate different views of an identity much better for familiar than for unfamiliar faces. However, a robust and consistent neural index of this behavioral face identity familiarity effect (FIFE)-not found in non-human primate species-is lacking. Here we provide such a neural FIFE index, measured implicitly and with one fixation per face. Fourteen participants viewed 70 s stimulation sequences of a large set (n = 40) of widely variable natural images of a face identity at a rate of 6 images/second (6 Hz). Different face identities appeared every 5th image (1.2 Hz). In a sequence, face images were either familiar (i.e., famous) or unfamiliar, participants performing a non-periodic task unrelated to face recognition. The face identity recognition response identified at 1.2 Hz over occipital-temporal regions in the frequency-domain electroencephalogram was 3.4 times larger for familiar than unfamiliar faces. The neural response to familiar faces-which emerged at about 180 ms following face onset-was significant in each individual but a case of prosopdysgnosia. Besides potential clinical and forensic applications to implicitly measure one's knowledge of a face identity, these findings open new perspectives to clarify the neurofunctional source of the FIFE and understand the nature of human face identity recognition.

Machine Learning-Enhanced Biomass Pressure Sensor with Embedded Wrinkle Structures Created by Surface Buckling.

Flexible piezoresistive sensors are core components of many wearable devices to detect deformation and motion. However, it is still a challenge to conveniently prepare high-precision sensors using natural materials and identify similar short vibration signals. In this study, inspired by microstructures of human skins, biomass flexible piezoresistive sensors were prepared by assembling two wrinkled surfaces of konjac glucomannan and k-carrageenan composite hydrogel. The wrinkle structures were conveniently created by hardness gradient-induced surface buckling and coated with MXene sheets to capture weak pressure signals. The sensor was applied to detect various slight body movements, and a machine learning method was used to enhance the identification of similar and short throat vibration signals. The results showed that the sensor exhibited a high sensitivity of 5.1 kPa-1 under low pressure (50 Pa), a fast response time (104 ms), and high stability over 100 cycles. The XGBoost machine learning model accurately distinguished short voice vibrations similar to those of individual English letters. Moreover, experiments and numerical simulations were carried out to reveal the mechanism of the wrinkle structure preparation and the excellent sensing performance. This biomass sensor preparation and the machine learning method will promote the optimization and application of wearable devices.

Intracerebral electrical stimulation of the face-selective right lateral fusiform gyrus transiently impairs face identity recognition.

Neuroimaging and intracranial electrophysiological studies have consistently shown the largest and most consistent face-selective neural activity in the middle portion of the human right lateral fusiform gyrus ('fusiform face area(s)', FFA). Yet, direct evidence for the critical role of this region in face identity recognition (FIR) is still lacking. Here we report the first evidence of transient behavioral impairment of FIR during focal electrical stimulation of the right FFA. Upon stimulation of an electrode contact within this region, subject CJ, who shows typical FIR ability outside of stimulation, was transiently unable to point to pictures of famous faces among strangers and to match pictures of famous or unfamiliar faces presented simultaneously for their identity. Her performance at comparable tasks with other visual materials (written names, pictures of buildings) remained unaffected by stimulation at the same location. During right FFA stimulation, CJ consistently reported that simultaneously presented faces appeared as being the same identity, with little or no distortion of the spatial face configuration. Independent electrophysiological recordings showed the largest neural face-selective and face identity activity at the critical electrode contacts. Altogether, this extensive multimodal case report supports the causal role of the right FFA in FIR.

Single neuron responses underlying face recognition in the human midfusiform face-selective cortex.

Faces are critical for social interactions and their recognition constitutes one of the most important and challenging functions of the human brain. While neurons responding selectively to faces have been recorded for decades in the monkey brain, face-selective neural activations have been reported with neuroimaging primarily in the human midfusiform gyrus. Yet, the cellular mechanisms producing selective responses to faces in this hominoid neuroanatomical structure remain unknown. Here we report single neuron recordings performed in 5 human subjects (1 male, 4 females) implanted with intracerebral microelectrodes in the face-selective midfusiform gyrus, while they viewed pictures of familiar and unknown faces and places. We observed similar responses to faces and places at the single cell level, but a significantly higher number of neurons responding to faces, thus offering a mechanistic account for the face-selective activations observed in this region. Although individual neurons did not respond preferentially to familiar faces, a population level analysis could consistently determine whether or not the faces (but not the places) were familiar, only about 50 ms after the initial recognition of the stimuli as faces. These results provide insights into the neural mechanisms of face processing in the human brain.

High-resolution myelin-water fraction and quantitative relaxation mapping using 3D ViSTa-MR fingerprinting.

Purpose: This study aims to develop a high-resolution whole-brain multi-parametric quantitative MRI approach for simultaneous mapping of myelin-water fraction (MWF), T1, T2, and proton-density (PD), all within a clinically feasible scan time. Methods: We developed 3D ViSTa-MRF, which combined Visualization of Short Transverse relaxation time component (ViSTa) technique with MR Fingerprinting (MRF), to achieve high-fidelity whole-brain MWF and T1/T2/PD mapping on a clinical 3T scanner. To achieve fast acquisition and memory-efficient reconstruction, the ViSTa-MRF sequence leverages an optimized 3D tiny-golden-angle-shuffling spiral-projection acquisition and joint spatial-temporal subspace reconstruction with optimized preconditioning algorithm. With the proposed ViSTa-MRF approach, high-fidelity direct MWF mapping was achieved without a need for multi-compartment fitting that could introduce bias and/or noise from additional assumptions or priors. Results: The in-vivo results demonstrate the effectiveness of the proposed acquisition and reconstruction framework to provide fast multi-parametric mapping with high SNR and good quality. The in-vivo results of 1mm- and 0.66mm-iso datasets indicate that the MWF values measured by the proposed method are consistent with standard ViSTa results that are 30x slower with lower SNR. Furthermore, we applied the proposed method to enable 5-minute whole-brain 1mm-iso assessment of MWF and T1/T2/PD mappings for infant brain development and for post-mortem brain samples. Conclusions: In this work, we have developed a 3D ViSTa-MRF technique that enables the acquisition of whole-brain MWF, quantitative T1, T2, and PD maps at 1mm and 0.66mm isotropic resolution in 5 and 15 minutes, respectively. This advancement allows for quantitative investigations of myelination changes in the brain.

Systemic lupus erythematosus with disseminated aspergillosis misdiagnosed as lupus encephalopathy: a case report and literature review.

Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Patients with SLE presenting sudden vision lost with intracranial and intrathoracic space-occupying lesions are distinctly rare clinically. People may be simply consider this multiple damages with disease activity. The process of differential diagnosis requires rigour and efficiency in both its thoroughness and efficiency. Because of their immunosuppressive state, patients with SLE are susceptible to infection than general population, which may be misdiagnosed as immune disorder. Case Description: In this article, we present a case of 40-year-old woman suspected with SLE at 1.5 years ago. In December 2020, this patient experienced with high fever, lupus hepatitis and autoimmune hemolytic anemia and thrombocytopenia, for which she was administered glucocorticoids and rituximab. Her symptoms were relieved and the dosage of prednisolone were gradually reduced to 15 mg per day. In May 2021, she experienced a sudden bilateral loss of vision. Ophthalmic examination showed posterior uveitis intracranial space-occupying lesions. Contrast-enhanced head magnetic resonance imaging (MRI) and chest computed tomography (CT) both showed multiple abnormal foci. According to the past history of SLE, the ophthalmology department of the local hospital misdiagnosed as lupus encephalopathy with uveitis. Unfortunately, the patient's vision didn't improve after she received high-dose glucocorticoid therapy. The patient was then transferred to our hospital. We measured her SLEDAI-2k score which was only 0 point. According to the humoral immunity is prevalently low, infectious causes should be considered firstly. We performed lumbar puncture for her, but the next-generation sequencing (NGS) of cerebrospinal fluid did not provide a significant sign for infection. Further, we performed an emergent vitreous tap and finally confirmed by the NGS of the vitreous fluid, that it was a multi-site infection caused by disseminated aspergillosis. Following anti-infective treatment, the patient's lung and intracranial lesions were absorbed; however, her vision was not restored. Conclusions: We experienced a rare case of disseminated aspergillosis which was misdiagnosed as lupus encephalopathy. Infectious causes should always be at the top on the list of differential diagnoses when people with SLE accompanying by uveitis or multiple system damage. The bacterial culture of the vitreous fluid may aid in the diagnosis of infectious endophthalmitis.

Central role of microglia in sepsis-associated encephalopathy: From mechanism to therapy.

Sepsis-associated encephalopathy (SAE) is a cognitive impairment associated with sepsis that occurs in the absence of direct infection in the central nervous system or structural brain damage. Microglia are thought to be macrophages of the central nervous system, devouring bits of neuronal cells and dead cells in the brain. They are activated in various ways, and microglia-mediated neuroinflammation is characteristic of central nervous system diseases, including SAE. Here, we systematically described the pathogenesis of SAE and demonstrated that microglia are closely related to the occurrence and development of SAE. Furthermore, we comprehensively discussed the function and phenotype of microglia and summarized their activation mechanism and role in SAE pathogenesis. Finally, this review summarizes recent studies on treating cognitive impairment in SAE by blocking microglial activation and toxic factors produced after activation. We suggest that targeting microglial activation may be a putative treatment for SAE.

Establishment and Evaluation of Artificial Intelligence-Based Prediction Models for Chronic Kidney Disease under the Background of Big Data.

Objective: To establish a prediction model for the risk evaluation of chronic kidney disease (CKD) to guide the management and prevention of CKD. Methods: A total of 1263 patients with CKD and 1948 patients without CKD admitted to the Tongde Hospital of the Zhejiang Province from January 1, 2008, to December 31, 2018, were retrospectively analyzed. Spearman's correlation was used to analyze the relationship between CKD and laboratory parameters. XGBoost, random forest, Naive Bayes, support vector machine, and multivariate logistic regression algorithms were employed to establish prediction models for the risk evaluation of CKD. The accuracy, precision, recall, F1 score, and area under the receiver operating curve (AUC) of each model were compared. The new bidirectional encoder representations from transformers with light gradient boosting machine (MD-BERT-LGBM) model was used to process the unstructured data and transform it into researchable unstructured vectors, and the AUC was compared before and after processing. Results: Differences in laboratory parameters between CKD and non-CKD patients were observed. The neutrophil ratio and white blood cell count were significantly associated with the occurrence of CKD. The XGBoost model demonstrated the best prediction effect (accuracy = 0.9088, precision = 0.9175, recall = 0.8244, F1 score = 0.8868, AUC = 0.8244), followed by the random forest model (accuracy = 0.9020, precision = 0.9318, recall = 0.7905, F1 score = 0.581, AUC = 0.9519). Comparatively, the predictions of the Naive Bayes and support vector machine models were inferior to those of the logistic regression model. The AUC of all models was improved to some extent after processing using the new MD-BERT-LGBM model. Conclusion: The new MD-BERT-LGBM model with the inclusion of unstructured data has contributed to the higher accuracy, sensitivity, and specificity of the prediction models. Clinical features such as age, gender, urinary white blood cells, urinary red blood cells, thrombin time, serum creatinine, and total cholesterol were associated with CKD incidence.

Circulating Exosomal miRNAs as Novel Biomarkers Perform Superior Diagnostic Efficiency Compared With Plasma miRNAs for Large-Artery Atherosclerosis Stroke.

Recently, exosomal miRNAs have been reported to be associated with some diseases, and these miRNAs can be used for diagnosis and treatment. However, diagnostic biomarkers of exosomal miRNAs for ischemic stroke have rarely been studied. In the present study, we aimed to identify exosomal miRNAs that are associated with large-artery atherosclerosis (LAA) stroke, the most common subtype of ischemic stroke; to further verify their diagnostic efficiency; and to obtain promising biomarkers. High-throughput sequencing was performed on samples from 10 subjects. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed on exosomes and plasma in the discovery phase (66 subjects in total) and the validation phase (520 subjects in total). We identified 5 candidate differentially expressed miRNAs (miR-369-3p, miR-493-3p, miR-379-5p, miR-1296-5p, and miR-1277-5p) in the discovery phase according to their biological functions, 4 of which (miR-369-3p, miR-493-3p, miR-379-5p, and miR-1296-5p) were confirmed in the validation phase. These four exosomal miRNAs could be used to distinguish LAA samples from small artery occlusion (SAO) samples, LAA samples from atherosclerosis (AS) samples, and LAA samples from control samples and were superior to plasma miRNAs. In addition, composite biomarkers achieved higher area under the curve (AUC) values than single biomarkers. According to our analysis, the expression levels of exosomal miR-493-3p and miR-1296-5p were negatively correlated with the National Institutes of Health Stroke Scale (NIHSS) score. The four identified exosomal miRNAs are promising biomarkers for the diagnosis of LAA stroke, and their diagnostic efficiency is superior to that of their counterparts in plasma.

Superparamagnetic Iron Oxide Nanoparticles and Static Magnetic Field Regulate Neural Stem Cell Proliferation.

Neural stem cells (NSCs) transplantation is a promising approach for the treatment of various neurodegenerative diseases. Superparamagnetic iron oxide nanoparticles (SPIOs) are reported to modulate stem cell behaviors and are used for medical imaging. However, the detailed effects of SPIOs under the presence of static magnetic field (SMF) on NSCs are not well elucidated. In this study, it was found that SPIOs could enter the cells within 24 h, while they were mainly distributed in the lysosomes. SPIO exhibited good adhesion and excellent biocompatibility at concentrations below 500 µg/ml. In addition, SPIOs were able to promote NSC proliferation in the absence of SMF. In contrast, the high intensity of SMF (145 ± 10 mT) inhibited the expansion ability of NSCs. Our results demonstrate that SPIOs with SMF could promote NSC proliferation, which could have profound significance for tissue engineering and regenerative medicine for SPIO applications.

Neurite Extension and Orientation of Spiral Ganglion Neurons Can Be Directed by Superparamagnetic Iron Oxide Nanoparticles in a Magnetic Field.

INTRODUCTION: Neuroregeneration is a major challenge in neuroscience for treating degenerative diseases and for repairing injured nerves. Numerous studies have shown the importance of physical stimulation for neuronal growth and development, and here we report an approach for the physical guidance of neuron orientation and neurite growth using superparamagnetic iron oxide (SPIO) nanoparticles and magnetic fields (MFs). METHODS: SPIO nanoparticles were synthesized by classic chemical co-precipitation methods and then characterized by transmission electron microscope, dynamic light scattering, and vibrating sample magnetometer. The cytotoxicity of the prepared SPIO nanoparticles and MF was determined using CCK-8 assay and LIVE/DEAD assay. The immunofluorescence images were captured by a laser scanning confocal microscopy. Cell migration was evaluated using the wound healing assay. RESULTS: The prepared SPIO nanoparticles showed a narrow size distribution, low cytotoxicity, and superparamagnetism. SPIO nanoparticles coated with poly-L-lysine could be internalized by spiral ganglion neurons (SGNs) and showed no cytotoxicity at concentrations less than 300 µg/mL. The neurite extension of SGNs was promoted after internalizing SPIO nanoparticles with or without an external MF, and this might be due to the promotion of growth cone development. It was also confirmed that SPIO can regulate cell migration and can direct neurite outgrowth in SGNs preferentially along the direction imposed by an external MF. CONCLUSION: Our results provide a fundamental understanding of the regulation of cell behaviors under physical cues and suggest alternative treatments for sensorineural hearing loss caused by the degeneration of SGNs.