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To investigate the potential effects of MRI protocols on brain FDG uptake in simultaneous PET/MR imaging.Seventy healthy subjects and ten patients with temporal lobe epilepsy were enrolled. Healthy subjects were divided to three groups to undergo different PET/MR scan protocols: "continuous MRI" with MRI stimulation presented during the whole scan, "late MRI" with MRI stimulation started after 40 min glucose uptake, and "no MRI" without MRI stimulation at all. Region-wise and voxel-wise differences in FDG uptake among the three protocols were compared. All epilepsy patients were scanned with the "continuous MRI" scan protocol. The effects of MRI protocol stimulation on pathological interpretation were evaluated.Highest global averaged metabolism was found in the normal dataset with continuous MRI scan protocol (P 0.05). Specifically, we observed higher FDG uptake in the primary auditory cortex, putamen, and lower FDG uptake in the occipital lobe and cerebellum during the "continuous MRI" scan protocol. However, MRI protocol stimulation after 40 min glucose uptake did not cause any significant differences in FDG uptake. Respectively compared to the normal dataset, patients with epilepsy showed consistent hypometabolism in the temporal lobe. Besides, significant metabolism changes in the primary auditory cortex, vermis, and occipital lobe were found in the "late MRI" protocol.The effects of MRI protocol on brain FDG uptake were varied. The effects, including from other practical setting, were conspicuous for scans where MRI protocol started immediately after glucose uptake, but would dramatically decrease to negligible 40 min later. Hence, it would be necessary for pathology studies to collect data from a normal control group using the same scan protocol for unbiased evaluation.

Enzyme cascade reactions that integrate natural enzymes and nanozymes have attracted intensive attention in biomedical studies. Nevertheless, it is still an important challenge to design simple, high-performance and safe cascade reaction systems. Herein, we constructed a cascade reactor Pd-Ru/GOx, in which two-dimensional Pd-Ru nanosheets (NSs) with excellent peroxidase (POD)-like activity were employed as a carrier for the covalent grafting of glucose oxidase (GOx) by glutaraldehyde coupling chemistry. The designed Pd-Ru/GOx cascade reactor possesses both GOx and POD-like activities and can not only transform non-toxic glucose into toxic hydroxyl radicals (˙OH) but also decrease the pH value of the reaction system to improve catalytic activity, achieving dual effects of cascade synergy and promotion. The

Purpose: To evaluate morphometric analysis program (MAP) and quantitative positron emission tomography (QPET) in epileptogenic zone (EZ) identification using a simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) system in MRI-negative epilepsies.Methods: Seventy-one localization-related MRI-negative epilepsies underwent preoperative simultaneous PET/MRI examination and surgical resection were enrolled retrospectively. MAP was performed on T1-weighted volumetric sequence and QPET was analyzed using statistical parametric mapping (SPM) with comparison to age-, and gender- matched normal controls. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MAP, QPET, MAP+ QPET and MAP/QPET in EZ localization were assessed. The correlations between surgical outcome and modalities concordant with cortical resection were analyzed.Results: Forty-five (63.4%) patients had Engel I seizure outcome. The sensitivity, specificity, PPV and NPV of MAP was 64.4%, 69.2%, 78.3% and 52.9%, respectively. The sensitivity, specificity, PPV, NPV of QPET was 73.3%, 65.4%, 78.6%, and 58.6%, respectively. MAP+QPET, defined as two tests concordant with cortical resection, had reduced sensitivity (53.3%) but increased specificity (88.5%) relative to individual tests. MAP/QPET, defined as one or both tests concordant with cortical resection, had increased sensitivity (86.7%) but reduced specificity (46.2%) relative to individual tests. The regions determined by MAP, QPET, MAP+QPET or MAP/QPET concordant with cortical resection was significantly associated with seizure-free outcome, MAP+QPET performed best. Conclusion: The combination of MAP and QPET imaging play a complementary role in EZ localization and this approach can be readily improved surgical outcome in MRI-negative epilepsies.

Background: The anterior cingulate cortex (ACC) seems to play an important role in behavioral deficits and executive dysfunctions in patients with behavioral variant frontotemporal dementia (bvFTD), while its specific and independent contribution requires clarification. Objective: To identify whether ACC abnormalities in gray matter (GM) volume and standardized uptake value ratio (SUVR) images are associated with disease severity of bvFTD, by analyzing hybrid T1 and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). Methods: We enrolled 21 bvFTD patients and 21 healthy controls in the study. Each subject underwent a hybrid PET/MRI study and a standardized neuropsychologic assessment battery. GM volume and SUVR are voxel-wise calculated and compared. Then we estimate the mean value inside ACC for further partial Pearson’s correlation to explore the association between GM volume/SUVR of the ACC and severity of behavioral deficit as well as executive dysfunction. Results: ACC was shown to be involved in both atrophy and hypometabolism patterns. The partial Pearson’s correlation analysis showed that the SUVR of the ACC was strongly correlated with frontal behavior inventory total score (left r = –0.85, right r = –0.85, p

Recently, rapid progress has been made in the application of organic-inorganic halide perovskites in electronic devices, such as memristors and artificial synaptic devices. Organic-inorganic halide perovskite is considered as a promising candidate for the next generation of computing devices due to its ion migration property and advantages in manufacturing. In this work, a two-dimensional (2D)-3D organic-inorganic hybrid perovskite memristor was studied, using the stacking structure of indium tin oxide (ITO)/FA1−yMAyPbI3−xClx/(PEA)2PbI4/Au. The results show that this new type of memristor has novel resistance switching characteristics, such as scanning-rate-dependent current switching property, good current-voltage (I–V) curve repeatability, and ultralow energy consumption. A defect-modulated electron tunneling mechanism is demonstrated using the p-i-n junction model, and it is proven that the conductance state of the memristive device is determined by the defect concentration in the perovskite film near the electrode sides. In addition to the good memristive properties, this 2D-3D perovskite memristor can also function well as an artificial synapse, and its internal defect movement can faithfully simulate the inflow and extrusion of Ca2+ in biological synapses. Moreover, this perovskite-based artificial synapse has ultra-low power consumption due to the switchable p-i-n structure in organic-inorganic halide perovskites. Our finding highlights the immense application potential of the 2D-3D perovskite memristor in the future neuromorphic computing system. Ministry of Education (MOE) This work was financially supported by the National Natural Science Foundation of China (61674050, 62004056, and 61874158), the Project of Distinguished Young of Hebei Province (A2018201231), the Support Program for the Top Young Talents of Hebei Province (70280011807), the Hundred Persons Plan of Hebei Province (E2018050004 and E2018050003), the Supporting Plan for 100 Excellent Innovative Talents in Colleges and Universities of Hebei Province (SLRC2019018), the Special Project of Strategic Leading Science and Technology of Chinese Academy of Sciences (XDB44000000-7), the Special Support Funds for National High Level Talents (041500120001), Hebei Basic Research Special Key Project (F2021201045), the Science and Technology Project of Hebei Education Department (QN2020178 and QN2021026), and Singapore Ministry of Education (AcRF TIER 2-MOE2019-T2-2-075).

To evaluate the clinical value of the combination of [18F]FDG PET/MRI and magnetoencephalography (MEG) ([18F]FDG PET/MRI/MEG) in localizing the epileptogenic zone (EZ) in temporal lobe epilepsy (TLE) patients. Seventy-three patients with localization-related TLE who underwent [18F]FDG PET/MRI and MEG were enrolled retrospectively. PET/MRI images were interpreted by two radiologists; the focal hypometabolism on PET was identified using statistical parametric mapping (SPM). MEG spike sources were co-registered onto T1-weighted sequence and analyzed by Neuromag software. The clinical value of [18F]FDG PET/MRI, MEG, and PET/MRI/MEG in locating the EZ was assessed using cortical resection and surgical outcomes as criteria. The correlations between surgical outcomes and modalities concordant or non-concordant with cortical resection were analyzed. For 46.6% (34/73) of patients, MRI showed definitely structural abnormality concordant with surgical resection. SPM results of [18F]FDG PET showed focal temporal lobe hypometabolism concordant with surgical resection in 67.1% (49/73) of patients, while the concordant cases increased to 82.2% (60/73) patients with simultaneous MRI co-registration. MEG was concordant with surgical resection in 71.2% (52/73) of patients. The lobar localization was defined in 94.5% (69/73) of patients by the [18F]FDG PET/MRI/MEG. The results of PET/MRI/MEG concordance with surgical resection were significantly higher than that of PET/MRI or MEG (χ2 = 13.948, p

Realization of functional flexible artificial synapse is a significant step toward neuromorphic computing. Herein, a flexible artificial synapse based on ferroelectric tunnel junctions (FTJs) is demonstrated, using BiFeO3 (BFO) thin film as the functional layer. The inorganic single crystalline FTJs grown on rigid perovskite substrates at high temperatures are integrated with the flexible plastic substrates, by using the water-soluble Sr3Al2O6 (SAO) as the sacrificial layer and the following transfer. The transferred freestanding BFO thin film exhibits excellent ferroelectric properties. Moreover, the memristive properties and the brain-like synaptic learning performance of the flexible FTJs are investigated. The results show that multilevel resistance states were maintained well of the flexible artificial synapse, together with their stable synaptic learning properties. Our work indicates the promising opportunity of ferroelectric thin film based flexible synapse used in the future neuromorphic computing system.

Fully integrated wearable electronics that combine the extraordinary feature of incessant and on-body operation with the distinctive external equipment-free trait are the ultimate goal of modern wearables. Epidermal sweat and wound exudate, as two noninvasively accessible biofluids on/surrounding the skin, reflect underlying health conditions. However, the design of universal wearable sensors with the bifunctional capability to monitor both epidermal secretions is still a challenge. Here, a single bifunctional fully integrated wearable tracker for wirelessly, simultaneously, and dynamically in situ measuring multiple epidermal sweat or wound exudate biomarkers is propos. Considering the electrolytes (e.g., Na

Crossed cerebellar diaschisis (CCD) has been widely studied in hemispheric stroke but is less characterized in epilepsy. In this study, we used 18F-FDG PET/CT to investigate the risk factors for CCD and its prognostic value for intractable epilepsy caused by focal cortical dysplasia (FCD). One hundred medically intractable epilepsy patients pathologically diagnosed with FCD postoperatively were included and classified into two groups: CCD+ and CCD−. PET/CT images were analyzed qualitatively by visual assessment and semi-quantitatively using the absolute asymmetry index (|AI|). Clinical factors, including age, sex, body mass index (BMI), age at seizure onset, epilepsy duration, seizure type, seizure frequency, electroencephalography (EEG) and brain magnetic resonance imaging (MRI), were retrospectively assessed from medical records. Follow-up outcomes were evaluated according to the Engel classification at 3, 6, 12, 24 and 36 months postoperatively. Of the 100 patients, 77 (77.0%) were classified as CCD−, and 23 (23.0%) were classified as CCD + . CCD+ patients had a higher number of lobes involved on PET (3.61 ± 2.16 vs 2.26 ± 1.01, P

Coptis chinensis Franch. (CC), as a commonly used heat-clearing and toxin-resolving traditional Chinese herbal medicine, has gained increased attention for its anti-tumor activity. However, little is known about the anti-tumor angiogenesis effect of CC and its possible bioactive components. Also, it has been shown that temperature affects the quality of CC, albeit whether and how it affects the anti-angiogenic activity of CC is currently unknown.To determine the processing temperatures (40, 60, 80, 120, 140, 150, 160 and 200 °C) at which CC has the strongest anti-angiogenic effect and speculate the possible bioactive components.The q-CAM model was constructed to explore the anti-angiogenesis agents of CC. The angiogenesis inhibition effects of CC samples at different processing temperatures and its seven alkaloids were determined based on morphological observation and vascular area proportion analysis. UPLC-MS/MS was employed to screen the potent active components of CC on anti-angiogenesis.All the intervention by CC at different processing temperatures and its seven alkaloids could inhibit angiogenesis on q-CAM vessels, as evidenced by a poor vasular development in morphological observation and a low vascular area proportion in vascular quantitative analysis, most evident in CC processed at 40 °C and palmatine. LC-MS revealed that palmatine displayed strongest inhibitory effect on q-CAM vessels with a high absorption due to its stable structure. And the maternal nucleus transformation phenomenon of CC alkaloids was found in the quail embryo metabolism.The q-CAM models in conjunction with the UPLC-MS/MS technique could be a useful tool for assessing tumor angiogenesis and screening tumor-targeted medicines. Processing temperature can affect the anti-angiogenesis effect of CC because of its function on the content of alkaloids, and palmatine can be considered as a prospective anti-angiogenic drug.

18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) estimate brain activities from different aspects, including regional glucose uptake (rGU) by 18FDG-PET, regional cerebral blood flow (rCBF) by arterial spin labeling, and dynamic changes of deoxyhemoglobin by blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI). However, the relationships between them remain incompletely understood. In the current study, twenty-four subjects (14 males, 10 females) were recruited and investigated the correlation among rGU, rCBF, and BOLD fMRI-derived metrics reflecting the neural activity, including amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) by hybrid PET/fMRI. Correlation analyses were performed across subject and across space at both voxel level and region level, considering partial volume effects by adjusting for gray matter volume. Each pair of metrics showed significant across-space correlations. rGU against ReHo showed the highest mean correlation coefficients. rGU had higher correlations with three resting-state (RS) fMRI metrics than did ASL-rCBF. However, the across-subject correlations were not significant among functional modalities (rGU, rCBF, and RS-fMRI BOLD data) at either voxel level or region level even with a liberal threshold, except for significant across-subject correlation between RS-fMRI metrics (ALFF, ReHo, and DC). These comprehensive findings from hybrid PET/MR might provide complementary information to reveal the underlying mechanisms of the brain activity and open new perspective to interpret pathologic conditions.

Glucose oxidase (GOx)-mediated starvation therapy has demonstrated good application prospect in cancer treatment. However, the glucose- and oxygen-depletion starvation therapy still suffers from some limitations like low therapeutic efficiency and potential side effects to normal tissues. To overcome these disadvantages, herein a novel enzymatic cascade nanoreactor (Pd@Pt-GOx/hyaluronic acid (HA)) with controllable enzymatic activities was developed for high-efficiency starving-enhanced chemodynamic cancer therapy. The Pd@Pt-GOx/HA was fabricated by covalent conjugation of GOx onto Pd@Pt nanosheets (NSs), followed by linkage with hyaluronic acid (HA). The modification of HA on Pd@Pt-GOx could block the GOx activity, catalase (CAT)-like and peroxidase (POD)-like activities of Pd@Pt, reduce the cytotoxicity to normal cells and organs, and effectively target CD44-overexpressed tumors by active targeting and passive enhanced permeability and retention (EPR) effect. After endocytosis by tumor cells, the intracellular hyaluronidase (Hyase) could decompose the outer HA and expose Pd@Pt-GOx for the enzymatic cascade reaction. The GOx on the Pd@Pt-GOx could catalyze the oxidation of intratumoral glucose by O2 for cancer starvation therapy, while the O2 produced from the decomposition of endogenous H2O2 by the Pd@Pt with the CAT-like activity could accelerate the O2-dependent depletion of glucose by GOx. Meanwhile, the upregulated acidity and H2O2 content in the tumor region generated by GOx catalytic oxidation of glucose dramatically facilitated the pH-responsive POD-like activity of the Pd@Pt nanozyme, which then catalyzed degradation of the H2O2 to generate abundant highly toxic •OH, thereby realizing nanozyme-mediated starving-enhanced chemodynamic cancer therapy. In vitro and in vivo results indicated that the controllable, self-activated enzymatic cascade nanoreactors exerted highly efficient anticancer effects with negligible biotoxicity.

Emerging memristors can be used as artificial synapses for emulating memory and computational functions. In this work, inspired by the memristive properties of tantalum dioxide, we designed a memristor with a structure of TiN/Ta2O5−x/HfxZr1−xO2 (x=0.5)/Pt (TTHZOP). The device conductance can be continuously tuned by adjusting the voltage pulse parameters (i.e., amplitude, width, and number) of voltage sweeps. Furthermore, for both of negative and positive parts, the current-voltage curves of the sweep cycle appear to better adjust the gradual distribution in successive twenty cycles. According to the fine fitting results of twenty positive and negative current-voltage (I–V) curves, the probability of an electron jumping over an energy barrier and the width of the energy barrier were analyzed in detail. It is found that the electron tunneling mechanism at the interface is responsible for gradual conduction change under successive external electrical stimulation consisting of both bulk and interface effects. The proposed TTHZOP memristor is a promising candidate in potential applications that mimic artificial biosynaptic adaptation and analog brain computation.

The development of conductive bridging random access memory (CBRAM) as an artificial synaptic device is an important step in the realization of an efficient biomimetic neural morphology computing system. In fact, CBRAM devices with simple substance electrodes often form unstable and discrete conductive filaments, thereby resulting in poor device performance. In this work, the effects of different alloy electrode ratios on the device performance were systematically investigated via electrode composition engineering. The devices (a kind of memristor) with an Ag-Cu ratio of 63:37 exhibited lower formation voltage and set voltage, better set voltage distribution uniformity, faster response speed, and lower power consumption than other devices. Moreover, the device is capable of emulating the biosynapse functions, including paired-pulse facilitation (PPF), post tetanic potentiation (PTP), spike-rate-dependent plasticity (SRDP), and spike-timing-dependent plasticity (STDP). Interestingly, the associative learning process of Pavlov’s dog experiment and aversion therapy were also realized without the use of complex external circuits. The use of electrode component engineering provides a new path for boosting the memristor properties via CBRAM devices, thereby laying the foundation for further development of neural morphology computing system.

Electronic synaptic devices with photoelectric sensing function are becoming increasingly important in the development of neuromorphic computing system. Here, we present a photoelectrical synaptic system based on high-quality epitaxial Ba0.6Sr0.4TiO3 (BST) films in which the resistance ramp characteristic of the device provides the possibility to simulate synaptic behavior. The memristor with the Pt/BST/Nb:SrTiO3 structure exhibits reliable I–V characteristics and adjustable resistance modulation characteristics. The device can faithfully demonstrate synaptic functions, such as potentiation and depression, spike time-dependent plasticity, and paired pulse facilitation, and the recognition accuracy of handwritten digits was as high as 92.2%. Interestingly, the functions of visual perception, visual memory, and color recognition of the human eyes have also been realized based on the device. This work will provide a strong candidate for the neuromorphic computing hardware system of photoelectric synaptic devices.

To investigate the individual measures of brain glucose metabolism, neural activity obtained from simultaneousThirty-nine unilateral mTLE-HS patients who underwent anterior temporal lobectomy were classified as having completely seizure-free (Engel class IA; n = 22) or non-seizure-free (Engel class IB-IV; n = 17) outcomes at 1 year after surgery. Preoperative [The machine learning classification model showed [Machine learning model suggests individual [• Individual [

Memristors with gradual conduction modulation can store and process information simultaneously similar to the way biological synapses function by adjusting the connections between two neighboring neurons. However, developing a memristor device with high stability, high uniformity and low power consumption is a challenge in neuromorphic computing applications. In this work, a two-terminal memristor with a Ta/Ta2O5/AlN/graphene structure was prepared using a multi-layer graphene film as the bottom electrode. The device exhibits stable electrical characteristics at a direct current scan voltage. More importantly, this memristor can fully simulate the function and plasticity of biological synapses, including spiking-time-dependent plasticity, and excitatory postsynaptic current among others. The energy value of a write event can be as low as 37 femtojoule through a pulse with 0.8 V amplitude and 50 ns width, further demonstrating the low power consumption. According to the fitting results of the current–voltage curve, the conduction mechanism was ascribed to trap assisted tunneling. The Ta/Ta2O5/AlN/graphene memristor provides an excellent candidate for achieving artificial synaptic neuromorphic computing with stability and low power consumption.

Artificial electronic synapses must be developed for the effective implementation of artificial neural networks in machine learning. Memristors that mimic the functions of biological synapses have drawn enormous interest because of their potential applications in microelectronic chips. Herein, for the first time, a new function in the phenomenological model, namely the principle of refractory period function, is developed based on a W/ZnO/FTO memristor device. The two decay rates of the device obtained through applying a voltage pulse can faithfully emulate repolarization and hyperpolarization of the refractory action potential. Furthermore, by applying two different pulse trains, the absolute refractory period and the relative refractory period were also mimicked. High-resolution transmission electron microscopy observations clearly show that W diffuses into the ZnO film and forms a W-conductive protruding region between the W and FTO electrodes in the device in the “ON” state. The experimentally demonstrated refractory period function represents significant progress in the neuromorphic emulation of the functionalities of the biological synapse.