A Case of Pregnancy-Induced Hereditary Thrombotic Thrombocytopenic Purpura Complicated by Cerebral Vasospasm.

BACKGROUND: The aim was to explore the treatment of a case of congenital thrombotic thrombocytopenic purpura induced by pregnancy complicated with cerebral vasospasm. METHODS: We present a case study of congenital TTP where disease onset occurred during two separate pregnancies. Interestingly, the disease course exhibited distinct differences on each occasion. Additionally, following plasma transfusion therapy, there was a transient occurrence of cerebral vasospasm. RESULTS: In this case, ADAMTS13 levels reached their lowest point three days after delivery during the first pregnancy, triggering morbidity. Remarkably, a single plasma transfusion of 400 mL sufficed for the patient's recovery. Nonetheless, a recurrence of symptoms transpired during her second pregnancy at 24 weeks of gestation. Plasma transfusions were administered during and after delivery. Sudden convulsions developed. ADAMTS13 ac-tivity returned to normal, but cranial MRA revealed constrictions in the intracranial segments of both vertebral arteries, the basilar artery, and the lumen of the anterior, middle, and posterior cerebral arteries. A subsequent cranial MRA conducted a month later showed no lumen stenosis, indicating spontaneous recovery. CONCLUSIONS: These findings highlight the importance of careful consideration when administering plasma transfusions in congenital TTP during pregnancy. Moreover, the development of novel therapeutic approaches such as recombinant ADAMTS13 is crucial for minimizing complications and optimizing patient care.

The novel probiotic preparation based on Lactobacillus spp. mixture on the intestinal bacterial community structure of Cherry Valley duck.

The development and utilization of probiotics have many environmental benefits when they are used to replace antibiotics in animal production. In this study, intestinal lactic acid bacteria were isolated from the intestines of Cherry Valley ducks. Probiotic lactic acid bacterial strains were screened for antibacterial activity and tolerance to produce a Lactobacillus spp. mixture. The effects of the compound on the growth performance and intestinal flora of Cherry Valley ducks were studied. Based on the results of the antibacterial activity and tolerance tests, the highly active strains Lactobacillus casei 1.2435, L. salivarius L621, and L. salivarius L4 from the intestines of Cherry Valley ducks were selected. The optimum ratio of L. casei 1.2435, L. salivarius L621, and L. salivarius L4 was 1:1:2, the amount of inoculum used was 1%, and the fermentation time was 14 h. In vivo experiments showed that compared with the control group, the relative abundances of intestinal Lactobacillus and Blautia were significantly increased in the experimental group fed the lactobacilli compound (P < 0.05); the relative abundances of Parabacteroides, [Ruminococcus]_torques_group, and Enterococcus were significantly reduced (P < 0.05), and the growth and development of the dominant intestinal flora were promoted in the Cherry Valley ducks. This study will provide more opportunities for Cherry Valley ducks to choose microecological agents for green and healthy breeding.

Decrease of lncRNA MEG3 in Acute Myeloid Leukemia Affected the Expression of p53 and MDM2.

BACKGROUND: The aim was to determine the clinical role of long non coding maternally expressed gene 3 (lncRNA MEG3) in adult acute myeloid leukemia (AML). METHODS: The expression levels of lncRNA MEG3 in bone marrow of AML patients and healthy donors were determined by qPCR. The correlation between expression levels of lncRNA MEG3 and clinical features was also analyzed. MTT assay and flow-cytometric assay were employed to determine the role of lncRNA MEG3 on the cell viability and apoptosis of AML cell lines. Expression levels of caspase-9, Bcl-2, MDM2, and p53 in those cells were determined by western blot. RESULTS: The expression levels of lncRNA MEG3 was significantly down-regulated in AML patients. Expression levels of lncRNA MEG3 were positively correlated with overall survival of patients. Up-regulation of lncRNA MEG3 could not only inhibit the cell growth and promoted apoptosis, but also increased the expression of caspase-9 and p53 and decreased the expression of Bcl-2 and MDM2. CONCLUSIONS: These results suggest that down-regulation of lncRNA MEG3 in AML patients might promote tumor progression and affect the p53-MDM2 pathway.

Prospective study on changes in the donor gallbladder contraction function after left lateral lobe hepatectomy.

This study aimed to evaluate the feasibility of donor gallbladder preservation in liver transplantation. Conventional removal of the donor gallbladder is applied in a majority of pediatric liver transplantation. A total of 42 donors who underwent gallbladder preservation in liver transplantation from October 2013 to December 2015 at the Beijing Friendship Hospital, China, were enrolled for the study. The changes in gallbladder volume and the gallbladder EF of donors before and after surgery were measured through ultrasound, and the changes in the donor gallbladder contraction function before and after surgery were evaluated to help verify the feasibility of gallbladder preservation in living donor left lateral lobe hepatectomy. The gallbladder emptying index dropped to 42.67% in 2 weeks after surgery and gradually increased with the length of recovery time, which could reach 69.14% in 3 months after surgery. At that time, 97.6% of the donors were considered to have recovered their gallbladder contraction function. The gallbladder contraction function at an early stage after gallbladder preservation in liver transplantation is not obviously improved, but it can recover to a normal level in 1 month after surgery, indicating that the gallbladder preservation in hepatectomy of living donor can effectively guarantee the gallbladder contraction function.

Ultrasound imaging in the diagnosis of benign and suspicious adrenal lesions.

BACKGROUND: The purpose of this study was to define the ultrasound imaging characteristics of adrenal tumors and to assess the performance of ultrasound in differentiating benign 'leave-alone' lesions from suspicious lesions. MATERIAL AND METHODS: We enrolled 882 patients in this study. The nature of each lesion was determined by histopathology. Ultrasound finding of each lesion was compared with its corresponding histopathologic result. The final study group consisted of 911 adrenal masses in 882 patients. All images were reviewed by 2 experienced investigators in a double blind manner. RESULTS: There were 553 adenomas identified in the study, which constituted 60.70% of the lesions. There were 161 pheochromocytomas (17.67%), 49 myelolipomas (5.38%), 39 cysts (4.28%), 37 metastasis (4.06%), 35 ganglioneuromas (3.84%), 22 lymphomas (2.41%), and 15 cortical carcinomas (1.65%). The sensitivity, specificity, and accuracy of ultrasound-based diagnosis were 89%, 99%, and 93.9%, respectively. A positive predictive value of 90.9% and a negative predictive value of 94.2% were obtained in this study. CONCLUSIONS: This large-sample study showed that ultrasound was a reliable method in differentiating benign 'leave-alone' lesions from suspicious lesions.

Prospective comparison of an 18-gauge versus 16-gauge needle for percutaneous liver core-needle biopsy in children.

PURPOSE: The objective of this study was to analyzed the impact of needle gauge (G) on the adequacy of specimens and hemorrhagic complications in pediatric patients undergoing ultrasound (US)-guided transplanted liver biopsies. METHODS: The study included 300 consecutive biopsies performed in 282 pediatric patients (mean age 6.75 ± 3.82 years, range 0.84-17.90) between December 2020 and April 2022. All pediatric patients that referred to our institution for US-guided core-needle liver biopsy (CNLB) were randomized to undergo 16-G or 18-G CNLB. Hemorrhagic complications were qualitatively evaluated. The number of complete portal tracts (CPTs) per specimen was counted and specimen adequacy was assessed based on the American Association for the Study of Liver Diseases guidelines. RESULTS: The incidence of bleeding was 7.00% (n = 21) and adequate specimens for accurate pathological diagnosis were obtained from 98.33% (n = 295) of patients. There was no significant difference in the incidence or amount of bleeding between the 16-G and 18-G groups (11 vs 10, p = 0.821; 35.0 mL vs 31.3 mL, p = 0.705). Although biopsies obtained using a 16-G needle contained more complete portal tracts than those obtained using an 18-G needle (20.0 vs 18.0, p = 0.029), there was no significant difference in specimen inadequacy according to needle gauge (2 vs 3, p = 1.000). CONCLUSIONS: Biopsy with a 16-G needle was associated with a greater number of CPTs but did not increase the adequate specimen rate. There was no significant difference in the complication rate between 16-G biopsy and 18-G biopsy.

Adsorption properties and mechanism of zinc acrylic carbon nanosphere aggregates for perfluorooctanoic acid from aqueous solution.

This study found that the cross-linkable zinc acrylic nanosphere aggregates (NAs) as precursors were successfully prepared by a simple one-step synthesis route, and Zn,O dopped-carbon nanocomposites were obtained through temperature-controllable engineering, which showed excellent adsorption capacities for perfluorooctanoic acid (PFOA). A series of experiments were performed to investigate and compare carbon materials for the efficient removal of PFOA. The maximum adsorption capacities of PFOA absorbed on carbon nanospheres aggregates (CNAs) were calculated by the Langmuir (360.98 mg/g) and Sips models (309.65 mg/g). The kinetic model indicated there was chemical adsorption and physical adsorption in the adsorption process. Van der Waals force and electrostatic interactions might be the dominant mechanism of the adsorption process. Additionally, pore-filling also played a role in the adsorption process. Furthermore, the adsorption efficiency was still above 90% after five cycles. The selective adsorption ability was tested through various pollutants (metal ions and dye solutions) absorbed by the CNAs. Our results proved that carbon nanosphere aggregates (CNAs) are expected to be outstanding adsorption materials for the decontamination of PFOA from wastewater.

High-performance multifunctional porous iron Acetylacetonate/N, O-doped carbon nanospheres for electromagnetic wave absorption at 2-18 GHz and methyl orange absorption.

Nowadays, multifunction is regarded as an advanced development direction of new-generation electromagnetic wave absorption (EMWA) materials to fulfill the ever-growing demands in complex environment and situation. Environmental pollution and electromagnetic pollution are all difficult problems for human beings all the time. Now, there is no multifunctional materials for collaborative treatment of environmental and electromagnetic pollution. Herein, We synthesized nanospheres with divinyl benzene (DVB) and N-[3-(dimethylamino)propyl]methacrylamide (DMAPMA), using a simple one-pot method. After calcination at 800 ℃ in N2, porous N, O-doped porous carbon materials were prepared. By regulating the mole ratio of DVB and DMAPMA, the ratio was 5:1 reached excellent EMWA property. Remarkably, the introduction of iron acetylacetonate into the reaction of DVB and DMAPMA was effective in enhancing the absorption bandwidth to 8.00 GHz at a 3.74 mm thickness, which depended on the synergistic effects from dielectric and magnetic losses. Simultaneously, the Fe-doped carbon materials had a methyl orange adsorption capacity. The adsorption isotherm conformed to the Freundlich model. After methyl orange absorption, the EMWA property did not greatly change. Thus, this research paves the way for the creation of multifunctional materials to solve environmental pollution and electromagnetic pollution together.

Preparation of magnetic sodium alginate/sodium carboxymethylcellulose interpenetrating network gel spheres and use in superefficient adsorption of direct dyes in water.

The rapid development of the printing and dyeing industry has led to the production of a large amount of high-density printing and dyeing wastewater, and technology for its effective treatment has become a focus of research. To construct a polymeric adsorbent material with abundant functional groups for the efficient adsorption of dye wastewater, a novel magnetic sodium alginate/carboxymethylcellulose interpenetrating network gel sphere (Fe3O4@SA/CMC-Fe) was prepared by co-blending sodium alginate (SA) and sodium carboxymethylcellulose (CMC) with Fe3O4; Fe3O4@SA/CMC-Fe was characterized by SEM-EDS, XRD, TGA, FT-IR, UV-Vis, VSM, BET-BJH and XPS. Static adsorption experiments showed that the optimal rates for adsorption of DV 51 and DR 23 from solutions with neutral pH values by Fe3O4@SA/CMC-Fe were up to 96 %, the adsorption process exhibited a Langmuir adsorption isotherm, and the dynamic adsorption process was accurately described by the pseudo-second-order kinetic model. A thermodynamic study showed that the adsorption reactions were all spontaneous exothermic reactions with increasing entropy. The mechanism for adsorption of the dyes by Fe3O4@SA/CMC-Fe involved hydrogen bonding, complexation and electrostatic adsorption. In summary, Fe3O4@SA/CMC-Fe is a green, simple, recyclable and highly efficient magnetic adsorbent that is expected to be widely used in treating dye wastewaters over a wide pH range.

Nanomaterial-based microelectrode arrays for in vitro bidirectional brain-computer interfaces: a review.

A bidirectional in vitro brain-computer interface (BCI) directly connects isolated brain cells with the surrounding environment, reads neural signals and inputs modulatory instructions. As a noninvasive BCI, it has clear advantages in understanding and exploiting advanced brain function due to the simplified structure and high controllability of ex vivo neural networks. However, the core of ex vivo BCIs, microelectrode arrays (MEAs), urgently need improvements in the strength of signal detection, precision of neural modulation and biocompatibility. Notably, nanomaterial-based MEAs cater to all the requirements by converging the multilevel neural signals and simultaneously applying stimuli at an excellent spatiotemporal resolution, as well as supporting long-term cultivation of neurons. This is enabled by the advantageous electrochemical characteristics of nanomaterials, such as their active atomic reactivity and outstanding charge conduction efficiency, improving the performance of MEAs. Here, we review the fabrication of nanomaterial-based MEAs applied to bidirectional in vitro BCIs from an interdisciplinary perspective. We also consider the decoding and coding of neural activity through the interface and highlight the various usages of MEAs coupled with the dissociated neural cultures to benefit future developments of BCIs.

PtNPs/rGO-GluOx/mPD Directionally Electroplated Dual-Mode Microelectrode Arrays for Detecting the Synergistic Relationship between the Cortex and Hippocampus of Epileptic Rats.

Precise and directional couplings of functional nanomaterials with implantable microelectrode arrays (IMEAs) are critical for the manufacture of sensitive enzyme-based electrochemical neural sensors. However, there is a gap between the microscale of IMEA and conventional bioconjugation techniques for enzyme immobilization, which leads to a series of challenges such as limited sensitivity, signal crosstalk, and high detection voltage. Here, we developed a novel method using carboxylated graphene oxide (cGO) to directionally couple the glutamate oxidase (GluOx) biomolecules onto the neural microelectrode to monitor glutamate concentration and electrophysiology in the cortex and hippocampus of epileptic rats under RuBi-GABA modulation. The resulting glutamate IMEA exhibited good performance involving less signal crosstalk between microelectrodes, lower reaction potential (0.1 V), and higher linear sensitivity (141.00 ± 5.66 nA µM-1 mm-2). The excellent linearity ranged from 0.3 to 68 µM (R = 0.992), and the limit of detection was 0.3 µM. For epileptic rats, the proposed IMEA sensitively obtained synergetic variations in the action potential (Spike), local field potentials (LFPs), and glutamate of the cortex and hippocampus during seizure and RuBi-GABA inhibition. We found that the increase in glutamate preceded the burst of electrophysiological signals. At the same time, both changes in the hippocampus preceded the cortex. This reminded us that glutamate changes in the hippocampus could serve as important indicators for early warning of epilepsy. Our findings provided a new technical strategy for directionally stabilizing enzymes onto the IMEA with versatile implications for various biomolecules' modification and facilitated the development of detecting tools for understanding the neural mechanism.

Using Human-Induced Pluripotent Stem Cell Derived Neurons on Microelectrode Arrays to Model Neurological Disease: A Review.

In situ physiological signals of in vitro neural disease models are essential for studying pathogenesis and drug screening. Currently, an increasing number of in vitro neural disease models are established using human-induced pluripotent stem cell (hiPSC) derived neurons (hiPSC-DNs) to overcome interspecific gene expression differences. Microelectrode arrays (MEAs) can be readily interfaced with two-dimensional (2D), and more recently, three-dimensional (3D) neural stem cell-derived in vitro models of the human brain to monitor their physiological activity in real time. Therefore, MEAs are emerging and useful tools to model neurological disorders and disease in vitro using human iPSCs. This is enabling a real-time window into neuronal signaling at the network scale from patient derived. This paper provides a comprehensive review of MEA's role in analyzing neural disease models established by hiPSC-DNs. It covers the significance of MEA fabrication, surface structure and modification schemes for hiPSC-DNs culturing and signal detection. Additionally, this review discusses advances in the development and use of MEA technology to study in vitro neural disease models, including epilepsy, autism spectrum developmental disorder (ASD), and others established using hiPSC-DNs. The paper also highlights the application of MEAs combined with hiPSC-DNs in detecting in vitro neurotoxic substances. Finally, the future development and outlook of multifunctional and integrated devices for in vitro medical diagnostics and treatment are discussed.

PtNPs/PEDOT:PSS-Modified Microelectrode Arrays for Detection of the Discharge of Head Direction Cells in the Retrosplenial Cortex of Rats under Dissociation between Visual and Vestibular Inputs.

The electrophysiological activities of head direction (HD) cells under visual and vestibular input dissociation are important to understanding the formation of the sense of direction in animals. In this paper, we fabricated a PtNPs/PEDOT:PSS-modified MEA to detect changes in the discharge of HD cells under dissociated sensory conditions. The electrode shape was customized for the retrosplenial cortex (RSC) and was conducive to the sequential detection of neurons at different depths in vivo when combined with a microdriver. The recording sites of the electrode were modified with PtNPs/PEDOT:PSS to form a three-dimensional convex structure, leading to closer contact with neurons and improving the detection performance and signal-to-noise ratio of the MEA. We designed a rotating cylindrical arena to separate the visual and vestibular information of the rats and detected the changes in the directional tuning of the HD cells in the RSC. The results showed that after visual and vestibular sensory dissociation, HD cells used visual information to establish newly discharged directions which differed from the original direction. However, with the longer time required to process inconsistent sensory information, the function of the HD system gradually degraded. After recovery, the HD cells reverted to their newly established direction rather than the original direction. The research based on our MEAs revealed how HD cells process dissociated sensory information and contributes to the study of the spatial cognitive navigation mechanism.

The contribution of strain patterns in characterization of prostate peripheral zone lesions at transrectal ultrasonography.

BACKGROUND: Elasticity is an important characteristic of tissue. During an elastography examination, various strain images of lesions are observed, and a suitable classification of strain patterns (SP) may provide vital diagnostic information about lesions. Numerous studies have shown that ultrasound elastography can improve the detection of prostate cancer, but the diagnostic value of SP classification has not yet been fully evaluated. PURPOSE: To investigate the contribution of SP on the characterization of prostate peripheral zone lesions by transrectal real-time tissue elastography (TRTE) in combination with conventional transrectal ultrasonography (TRUS). MATERIAL AND METHODS: One hundred and seventy-one patients with suspected prostate cancer underwent TRUS and TRTE examinations. The SPs of the suspicious lesions were classified into five scores by TRTE according to the degree and distribution of strain. All findings were confirmed by transrectal systematic 12-core biopsies and targeted biopsies for suspicious areas detecting by TRUS and/or TRTE. RESULTS: One hundred and forty-eight of 171 patients had high-quality TRTE imaging and were included into the study. When a cut-off point of SP score III was used, the area under the receiver-operating characteristic curve (AUC) was, respectively, 0.75 (95% CI: 0.67-0.83), 0.85 (95% CI: 0.78-0.91) and 0.84 (95% CI: 0.77-0.91) for the diagnosis of prostate cancer by TRUS, TRTE and TRTE + TRUS. A linear tendency of SP and Gleason scores was observed in scores III-V. The detection rate of prostate cancer using TRTE-targeted biopsy (75.8%) was significantly higher than that of systematic 12-core biopsy plus TRUS-targeted biopsy (14.5%) (P = 0.00). CONCLUSION: This study suggests the significant contribution of SP on characterization of prostate peripheral zone lesions and the improvement of TRTE-targeted biopsy on detection of prostate cancer.

Role of contrast-enhanced ultrasound in the differentiation of high- and low-grade urothelial carcinoma.

OBJECTIVE: To investigate the role of contrast-enhanced ultrasound in the differential diagnosis of high- and low-grade urothelial carcinoma. METHODS: The radiological data of 96 patients with urothelial carcinomas who had undergone gray-scale contrast-enhanced ultrasound from August 2010 to April 2011 were analyzed retrospectively. Pathological examination demonstrated that the tumors were high-grade in 55 cases (high-grade group) and low-grade in 41 cases (low-grade group). The dynamic images were analyzed by time-intensity curve, and the arrival time (AT), peak intensity (PI), time to peak (TTP), and washout time (WT) were measured. The enhancement patterns of different urothelial carcinomas were analyzed. RESULTS: Both PI (P=0.005) and WT (P=0.002) were significantly higher in high-grade group than in low-grade group, whereas AT (P=0.374) and TTP (P=0.386) showed no significant difference between these two groups. In the high-grade group, 47 cases (85.5%) were identified as fast wash-in and slow wash-out; in the low-grade group, 35 (85.4%) were identified as fast wash-in and fast wash-out. When the enhancement pattern was used as a diagnostic indicator for differentiating urothelial carcinomas, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 85.5%, 90.2%, 87.5%, 92.2%, and 82.2% for high-grade tumor and 85.4%, 90.9%, 88.5%, 87.5%, and 89.3% for low-grade tumor. CONCLUSIONS: Different grade urothelial carcinomas show different enhancement finding on contrast-enhanced ultrasound. The enhancement pattern can serve as an important diagnostic indicator.

[Establishment of a nomogram for predicting positive repeat prostate biopsy in Chinese men].

OBJECTIVE: To develop a nomogram for predicting the probability of prostate cancer at transrectal ultrasound-guided repeat prostate biopsy in Chinese men. METHODS: We performed repeat biopsy for 170 patients with benign prostate diseases diagnosed on the first biopsy, and analyzed the correlation of positive repeat biopsy with age, prostate volume, PSA, free-to-total PSA (f-PSA/t-PSA), PSA velocity, PSA density, results of digital rectal examination (DRE) and previous histology. We entered the variables stepwise into logistic regression models, and established a nomogram for the risk score on the probability of positive repeat biopsy, whose predictive value was assessed by receiver operating characteristic (ROC) analysis. RESULTS: Prostate cancer was detected in 31.8% of the repeat biopsies (54/170). The most accurate predictive nomogram comprised age, PSA, f-PSA/t-PSA, PSA velocity, prostate volume, DRE and previous prostatic intraepithelial neoplasia (PIN) findings. The nomogram exhibited a high predictive value, with the area under the ROC curve (AUC) of 82.4%, significantly greater than that of the prediction based on PSA density (AUC: 66.9%), prostate volume (AUC: 72.6%), PSA velocity (AUC: 69.6%), f-PSA/t-PSA (AUC: 69.3%), or DRE (AUC: 58.5% ) alone. CONCLUSION: The nomogram is an accurate multi-variable predicting tool to determine the probability of positive repeat prostate biopsy.

PtNPs/PEDOT:PSS-Modified Microelectrode Arrays Reveal Electrophysiological Activities of Different Neurons in Medial Amygdala of Mice Under Innate Fear.

The medial amygdala (MA) plays an important role in the innate fear circuit. However, the electrophysiological mechanism of MA for processing innate fear needs to be further explored. In this study, we fabricated microelectrode arrays (MEAs) with detecting sites arranged to match the location and shape of MA in mice and detected the electrophysiology in freely behaving mice under 2-methyl-2-thiazoline (2MT)-induced fear. The detection performance of MEA is improved by modifying metal nanoparticles and conductive polymers (PtNPs/PEDOT:PSS). After modification, the impedance magnitude and phase of electrodes were decreased to 27.0 ± 2.3 kΩ and -12.30 ± 0.52°, respectively, leading to a signal-to-noise ratio of 10. Its electrochemical stability and mechanical stability were also verified by cyclic voltammetry (CV) sweeping and ultrasonic vibration. MEAs were then implanted into the MA of mice, and the electrophysiology and behavioral characteristics were synchronously recorded and analyzed. The results showed that 2MT induced strong defensive behaviors in mice, accompanied by increases in the average spike firing rate and local field potential (LFP) power of MA neurons. According to principles commonly applied to cortical extracellular recordings, the recorded neurons are divided into two classes based on waveforms. Statistics showed that about 37% of type 1 neurons (putative GABAergic neurons) and 87% of type 2 neurons (putative glutamatergic neurons) were significantly activated under innate fear. At the same time, the firing rate of some activated neurons had a good linear correlation with the freezing rate.

Sensitive detection of electrophysiology and dopamine vesicular exocytosis of hESC-derived dopaminergic neurons using multifunctional microelectrode array.

Clinical transplantation of human embryonic stem cells derived dopaminergic neurons (hESC-DDNs) is expected to be a potential therapy for treating neurodegenerative diseases. However, the assessment of the physiological functions, including electrophysiology and dopamine (DA) vesicular exocytosis of hESC-DDNs are not impeccable currently, which deeply limits the clinical application of hESC-DDNs. To overcome this challenge, we developed a multifunctional microelectrode array (MEA) which can detect both electrophysiological signals and DA vesicular exocytosis. The reduced oxidation graphene, poly(3,4-ethylenedioxythiophene) and poly (sodium-4-styrenesultanate) nanocomposites (rGO/PEDOT:PSS) were electrochemically deposited on the MEAs to improve their electrical characterizations with low impedance and small phase delay, and electrochemical characterizations with low oxidation potential, low detection limit, high sensitivity, wide linear range and high sensitivity. In the hESC-DDNs experiment, the modified MEA could detect electrophysiological signals with low noise (25 µV) and high signal-to-noise ratio (>5.4), and the weak current signals generated by DA vesicular exocytosis with high sensitivity (∼pA), high time resolution (sub-millisecond) and low noise (3 pA). Moreover, due to increased accuracy, the MEA could clearly distinguish two typical kinds of exocytosis spike events ("Spikes with foot" and "Spikes without foot") and found that the slow and low release through the fusion pore was an important mode of DA vesicular exocytosis in hESC-DDNs. Our work proved that the hESC-DDNs had the basic physiological functions as human dopaminergic neurons, which would be beneficial to the clinical application of the hESC-DDNs.

A Neural Sensor with a Nanocomposite Interface for the Study of Spike Characteristics of Hippocampal Neurons under Learning Training.

Both the cellular- and population-level properties of involved neurons are essential for unveiling the learning and memory functions of the brain. To give equal attention to these two aspects, neural sensors based on microelectrode arrays (MEAs) have been in the limelight due to their noninvasive detection and regulation capabilities. Here, we fabricated a neural sensor using carboxylated graphene/3,4-ethylenedioxythiophene:polystyrenesulfonate (cGO/PEDOT:PSS), which is effective in sensing and monitoring neuronal electrophysiological activity in vitro for a long time. The cGO/PEDOT:PSS-modified microelectrodes exhibited a lower electrochemical impedance (7.26 ± 0.29 kΩ), higher charge storage capacity (7.53 ± 0.34 mC/cm2), and improved charge injection (3.11 ± 0.25 mC/cm2). In addition, their performance was maintained after 2 to 4 weeks of long-term cell culture and 50,000 stimulation pulses. During neural network training, the sensors were able to induce learning function in hippocampal neurons through precise electrical stimulation and simultaneously detect changes in neural activity at multiple levels. At the cellular level, not only were three kinds of transient responses to electrical stimulation sensed, but electrical stimulation was also found to affect inhibitory neurons more than excitatory neurons. As for the population level, changes in connectivity and firing synchrony were identified. The cGO/PEDOT:PSS-based neural sensor offers an excellent tool in brain function development and neurological disease treatment.

High-Throughput PEDOT:PSS/PtNPs-Modified Microelectrode Array for Simultaneous Recording and Stimulation of Hippocampal Neuronal Networks in Gradual Learning Process.

When it comes to mechanisms of brain functions such as learning and memory mediated by neural networks, existing multichannel electrophysiological detection and regulation technology at the cellular level does not suffice. To address this challenge, a 128-channel microelectrode array (MEA) was fabricated for electrical stimulation (ES) training and electrophysiological recording of the hippocampal neurons in vitro. The PEDOT:PSS/PtNPs-coated microelectrodes dramatically promote the recording and electrical stimulation performance. The MEA exhibited low impedance (10.94 ± 0.49 kohm), small phase delay (-12.54 ± 0.51°), high charge storage capacity (14.84 ± 2.72 mC/cm2), and high maximum safe injection charge density (4.37 ± 0.22 mC/cm2), meeting the specific requirements for training neural networks in vitro. A series of ESs at various frequencies was applied to the neuronal cultures in vitro, seeking the optimum training mode that enables the neuron to display the most obvious plasticity, and 1 Hz ES was determined. The network learning process, including three consecutive trainings, affected the original random spontaneous activity. Along with that, the firing pattern gradually changed to burst and the correlation and synchrony of the neuronal activity in the network have progressively improved, increasing by 314% and 240%, respectively. The neurons remembered these changes for at least 4 h. Collectively, ES activates the learning and memory functions of neurons, which is manifested in transformations in the discharge pattern and the improvement of network correlation and synchrony. This study offers a high-performance MEA revealing the underlying learning and memory functions of the brain and therefore serves as a useful tool for the development of brain functions in the future.