Novel Two-Terminal Synapse/Neuron Based on an Antiferroelectric Hafnium Zirconium Oxide Device for Neuromorphic Computing.

Functionally diverse devices with artificial neuron and synapse properties are critical for neuromorphic systems. We present a two-terminal artificial leaky-integrate-fire (LIF) neuron based on 6 nm Hf0.1Zr0.9O2 (HZO) antiferroelectric (AFE) thin films and develop a synaptic device through work function (WF) engineering. LIF neuron characteristics, including integration, firing, and leakage, are achieved in W/HZO/W devices due to the accumulated polarization and spontaneous depolarization of AFE HZO films. By engineering the top electrode with asymmetric WFs, we found that Au/Ti/HZO/W devices exhibit synaptic weight plasticity, such as paired-pulse facilitation and long-term potentiation/depression, achieving >90% accuracy in digit recognition within constructed artificial neural network systems. These findings suggest that AFE HZO capacitor-based neurons and WF-engineered artificial synapses hold promise for constructing efficient spiking neuron networks and artificial neural networks, thereby advancing neuromorphic computing applications based on emerging AFE HZO devices.

Low-power and high-speed HfLaO-based FE-TFTs for artificial synapse and reconfigurable logic applications.

Emulating the human nervous system to build next-generation computing architectures is considered a promising way to solve the von Neumann bottleneck. Transistors based on ferroelectric layers are strong contenders for the basic unit of artificial neural systems due to their advantages of high speed and low power consumption. In this work, the potential of Fe-TFTs integrating the HfLaO ferroelectric film and ultra-thin ITO channel for artificial synaptic devices is demonstrated for the first time. The Fe-TFTs can respond significantly to pulses as low as 14 ns with an energy consumption of 93.1 aJ, which is at the leading level for similar devices. In addition, Fe-TFTs exhibit essential synaptic functions and achieve a recognition rate of 93.2% for handwritten digits. Notably, a novel reconfigurable approach involving the combination of two types of electrical pulses to realize Boolean logic operations ("AND", "OR") within a single Fe-TFT has been introduced for the first time. The simulations of array-level operations further demonstrated the potential for parallel computing. These multifunctional Fe-TFTs reveal new hardware options for neuromorphic computing chips.

A Case of Urinary Tract Infection Caused by Multidrug Resistant Streptococcus mitis/oralis.

S. mitis/oralis has been previously reported in isolated cases of bacterial endocarditis and liver abscesses. Its presence in urine is generally considered a contaminant. A 66-year-old male patient was admitted to the hospital due to recurrent chest tightness and four-year history of exertional dyspnea. On the second day of admission, the patient presented with urgent and frequent urination, as well as dysuria. Both initial and subsequent urine cultures showed S. mitis/oralis infection, with polymorphonuclear leukocyte phagocytosis observed in the second sample. MALDI-TOF results confirmed the isolated strain as S. mitis/oralis. Drug susceptibility testing revealed multidrug resistance to penicillin, ceftriaxone, cefepime, levofloxacin, ofloxacin, and tetracycline, but sensitivity to quinupristin/dalfopristin, vancomycin, and linezolid. The clinician then prescribed vancomycin for anti-infective treatment, which proved effective. Keywords: S. mitis/oralis, UTI, MDR, phagocytosis.

Analysis of molecular characteristics of CAMP-negative Streptococcus agalactiae strains.

Background: Streptococcus agalactiae can produce CAMP factor, which can promote the ß-hemolysin activity of Staphylococcus aureus, forming an arrow-shaped hemolysis enhancement zone at the intersection of the two bacterial species on a blood agar plate. This characteristic feature of Streptococcus agalactiae has led to the widespread use of the CAMP test as an identification method. Methods: Vaginal/rectal swabs, collected from women at 35-37 weeks of pregnancy, were first inoculated into a selective enrichment broth media, then subcultured onto GBS chromogenic agar and 5% sheep blood agar sequentially. The VITEK-2 automatic identification system and MALDI-TOF MS were initially employed for identification, followed by the CAMP test. CAMP-negative strains underwent 16S rDNA and cfb gene sequence analysis, as well as bacterial multilocus sequence typing. Results: A total of 190 strains were isolated, with 15 identified as CAMP-negative. Further 16S rDNA gene sequence analysis confirmed that all 15 strains were Streptococcus agalactiae. The MLST typing assay revealed that these 15 strains were of the ST862 type. The cfb gene was amplified and electrophoresed, but no specific fragments were found, indicating that these strains lack the CAMP factor due to cfb gene deletion. Antibiotic susceptibility tests demonstrated no resistance to penicillin, ampicillin, vancomycin and linezolid among the GBS strains. However, there are significant differences in resistance rates to tetracycline. Conclusion: This study found that 7.9% of GBS strains isolated from the vagina/rectum of pregnant women were CAMP-negative, suggesting that the CAMP test method or primers targeting the cfb gene should not be used as the sole presumptive test for GBS identification.

Recent Progress and Perspectives on Photocathode Materials for CO2 Catalytic Reduction.

The continuous consumption of fossil energy and excessive emissions of carbon dioxide (CO2) have caused a serious energy crisis and led to the greenhouse effect. Using natural resources to convert CO2 into fuel or high-value chemicals is considered to be an effective solution. Photoelectrochemical (PEC) catalysis utilizes abundant solar energy resources, combined with the advantages of photocatalysis (PC) and electrocatalysis (EC), to achieve efficient CO2 conversion. In this review, the basic principles and evaluation criteria, of PEC catalytic reduction to CO2 (PEC CO2RR), are introduced. Next, the recent research progress on typical kinds of photocathode materials for CO2 reduction are reviewed, and the structure-function relationships between material composition/structure and activity/selectivity are discussed. Finally, the possible catalytic mechanisms and the challenges of using PEC to reduce CO2 are proposed.

Stable Plating and Stripping of Lithium Metal Anodes through Space Confinement and Stress Regulation.

Lithium metal anodes suffer from enormous mechanical stress derived from volume changes during electrochemical plating and stripping. The utilization of derived stress has the potential for the dendrite-free deposition and electrochemical reversibility of lithium metal. Here, we investigated the plating and stripping process of lithium metal held within a cellular three-dimensional graphene skeleton decorated with homogeneous Ag nanoparticles. Owing to appropriate reduction-splitting and electrostatic interaction of nitrogen dopants, the cellular skeletons show micron-level pores and superior elastic property. As lithium hosts, the cellular skeletons can physically confine the metal deposition and provide continuous volume-derived stress between Li and collectors, thus meliorating the stress-regulated Li morphology and improving the reversibility of Li metal anodes. Consequently, the symmetrical batteries exhibit a stable cycling performance with a span life of more than 1900 h. Full batteries (NCM811 as cathodes) achieve a reversible capacity of 181 mA h g-1 at 0.5 C and a stable cycling performance of 300 cycles with a capacity retention of 83.5%. The meliorative behavior of lithium metal within the cellular skeletons suggests the advantage of a stress-regulating strategy, which could also be meaningful for other conversion electrodes with volume fluctuation.

The Doping Effect on the Intrinsic Ferroelectricity in Hafnium Oxide-Based Nano-Ferroelectric Devices.

Hafnium oxide (HfO2)-based ferroelectric tunnel junctions (FTJs) have been extensively evaluated for high-speed and low-power memory applications. Herein, we investigated the influence of Al content in HfAlO thin films on the ferroelectric characteristics of HfAlO-based FTJs. Among HfAlO devices with different Hf/Al ratios (20:1, 34:1, and 50:1), the HfAlO device with Hf/Al ratio of 34:1 exhibited the highest remanent polarization and excellent memory characteristics and, thereby, the best ferroelectricity among the investigated devices. Furthermore, first-principal analyses verified that HfAlO thin films with Hf/Al ratio of 34:1 promoted the formation of the orthorhombic phase against the paraelectric phase as well as alumina impurities and, thus, enhanced the ferroelectricity of the device, providing theoretical support for supporting experimental results. The findings of this study provide insights for developing HfAlO-based FTJs for next-generation in-memory computing applications.

Effect of hyaluronic acid on cytokines and immune cells change in patients of knee osteoarthritis.

PURPOSE: To evaluate the changes of cytokines and immune cells after Intra-articular hyaluronic acid(IAHA)injections in patients with knee osteoarthritis (KOA). PATIENTS AND METHODS: Sixteen patients were included in the study, with a total of 65 IAHA injections. The Numeric Rating Scale (NRS) and Lysholm scores were evaluated at each visit. The immune cells and 14 cytokines of synovial fluid were analyzed at each visit. The association between immune cells and cytokines were examined. RESULTS: IL-6 and IL-8 were the most common cytokines in the synovial fluid of KOA patients. The synovial fluid was orchestrated by macrophages (69%) and Lymphocytes (18%). Neutrophils were less to count of the total cell population (< 2%). The cytokines decreased significantly after the first injection and then tended to be stable. Lymphocytes increased a lot, while Macrophages decreased in the early stage, then increased after multiple injections. The proposition of M1 decreased in the early stage, then increased after multiple injections, while M2 increased consistently. M1 and M2 were positively associated with IL-6 and IL-8. CONCLUSION: The synovial fluid of KOA patients was orchestrated by macrophages (69%) and Lymphocytes (18%) and cytokines like IL-6 and IL-8. IAHA may play an anti-inflammatory functional role through the decreased production of IL-6 and IL-8 by macrophages through polarization. The results from this study partially revealed the effect of IAHA on cytokines and immune cells change in KOA patients, and therapies targeting pathogenic cytokines and immune cells might be used to attenuate the knee joint inflammation and release pain. TRIAL REGISTRATION: ChiCTR2100050133; date registered 17 August 2021.

Neural substrates of motivational dysfunction across neuropsychiatric conditions: Evidence from meta-analysis and lesion network mapping.

Motivational dysfunction constitutes one of the fundamental dimensions of psychopathology cutting across traditional diagnostic boundaries. However, it is unclear whether there is a common neural circuit responsible for motivational dysfunction across neuropsychiatric conditions. To address this issue, the current study combined a meta-analysis on psychiatric neuroimaging studies of reward/loss anticipation and consumption (4308 foci, 438 contrasts, 129 publications) with a lesion network mapping approach (105 lesion cases). Our meta-analysis identified transdiagnostic hypoactivation in the ventral striatum (VS) for clinical/at-risk conditions compared to controls during the anticipation of both reward and loss. Moreover, the VS subserves a key node in a distributed brain network which encompasses heterogeneous lesion locations causing motivation-related symptoms. These findings do not only provide the first meta-analytic evidence of shared neural alternations linked to anticipatory motivation-related deficits, but also shed novel light on the role of VS dysfunction in motivational impairments in terms of both network integration and psychological functions. Particularly, the current findings suggest that motivational dysfunction across neuropsychiatric conditions is rooted in disruptions of a common brain network anchored in the VS, which contributes to motivational salience processing rather than encoding positive incentive values.

RNA modification patterns based on major RNA modifications define tumor microenvironment characteristics in glioblastoma.

RNA modifications play a major role in tumorigenicity and progression, but the expression and function in glioblastoma (GBM) have not been well described. In this study, we developed a GBM score based on the differentially expressed genes (DEGs) between groups showing RNA modification patterns. We assessed the association between the GBM score and tumor microenvironment (TME) characteristics. Based on the gene expression of these regulators, we identified two clusters with distinct RNA modification patterns. Kaplan-Meier survival curves showed that patients in cluster 1 had worse survival than those in cluster 2. Kaplan-Meier and multivariate Cox regression analyses showed that GBM scores (based on DEGs between RNA modification patterns) are an independent predictive biomarker for patient prognosis. Besides, we found that samples with high scores were significantly associated with epithelial-to-mesenchymal transition and immune checkpoints, while samples with low scores were associated with cell cycle regulation. Importantly, GBM-score markedly positively correlated drug resistance, while negatively correlated with drug sensitive. The responders of anti-PD-1/PD-L1 immunotherapy tend to have a lower GBM score than non-responders. In conclusion, our comprehensive analysis of multiple RNA modifications in GBM revealed that RNA modification regulators were closely correlated with TME.

Oxidative Injury in Ischemic Stroke: A Focus on NADPH Oxidase 4.

Ischemic stroke is a leading cause of disability and mortality worldwide. Thus, it is urgent to explore its pathophysiological mechanisms and find new therapeutic strategies for its successful treatment. The relationship between oxidative stress and ischemic stroke is increasingly appreciated and attracting considerable attention. ROS serves as a source of oxidative stress. It is a byproduct of mitochondrial metabolism but primarily a functional product of NADPH oxidases (NOX) family members. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is most closely related to the formation of ROS during ischemic stroke. Its expression is significantly upregulated after cerebral ischemia, making it a promising target for treating ischemic stroke. Several drugs targeting NOX4, such as SCM-198, Iso, G-Rb1, betulinic acid, and electroacupuncture, have shown efficacy as treatments of ischemic stroke. MTfp-NOX4 POC provides a novel insight for the treatment of stroke. Combinations of these therapies also provide new approaches for the therapy of ischemic stroke. In this review, we summarize the subcellular location, expression, and pathophysiological mechanisms of NOX4 in the occurrence and development of ischemic stroke. We also discuss the therapeutic strategies and related regulatory mechanisms for treating ischemic stroke. We further comment on the shortcomings of current NOX4-targeted therapy studies and the direction for improvement.

Enhanced air filtration performances by coating aramid nanofibres on a melt-blown nonwoven.

Nanofibre membranes with a small diameter and a large specific surface area are widely used in the filtration field due to their small pore size and high porosity. To date, aramid nanofibres (ANFs) have received extensive research interest because of their high stiffness and excellent temperature resistance. However, the preparation of ANFs usually takes a long time, which greatly hampers the practical application of these fibres. Herein, we report the preparation of ANFs by a modified deprotonation method at elevated temperature. Owing to the increase of temperature, the preparation cycle of ANFs was shortened to 8 hours. The resulting ANF dispersion was further coated on a polypropylene melt-blown nonwoven to form a composite nonwoven filter. With the submicron porous structure, the filtration efficiency, pressure drop and quality factor of the filter were 95.61%, 38.22 Pa and 0.082 Pa-1, respectively. Compared to the pristine nonwoven, the filtration, mechanical, and heat insulation properties of the composite filter were also significantly improved. This work may offer a simple and efficient way for enhancing the air filtration performances of current filters.

Chemical Buffer Layer Enabled Highly Reversible Zn Anode for Deeply Discharging and Long-Life Zn-Air Battery.

Rechargeable alkaline Zn-air batteries (ZABs) are attracting extensive attention owing to their high energy density and environmental friendliness. However, the dilemma of Zn anode, composed of ineluctable passivation and dissolution problems, severely hinders the discharge and cycling performance of the battery. Herein, the authors propose a chemical buffer layer coated on Zn metal (CBL@Zn) anode, in which ZnO nanorods are uniformly dispersed in graphene oxide (GO), to improve the reversibility of Zn↔ZnO electrochemical conversion process. Benefiting from the cooperative effect of ZnO nanorods' nuclei role and GO's adsorption affinity, the electrochemical precipitation-dissolution behavior of insulated ZnO is chemically regulated and the Zn(OH)4 2- ions are effectively confined in the chemical buffer layer. Therefore, the symmetrical CBL@Zn-CBL@Zn coin cell achieves a superior stability of 100 cycles with quite low overpotential (30 mv). When paired with commercial catalysts to assemble alkaline ZABs for practical use, an ultra high depth of discharge (DODZn ) >98% and excellent 450-h long-term cycling performance are realized. This chemical buffer strategy can potentially provide a new insight for developing other highly reversible alkaline Zn-metal batteries.

Metabolic Signature-Based Subtypes May Pave Novel Ways for Low-Grade Glioma Prognosis and Therapy.

Metabolic signatures are frequently observed in cancer and are starting to be recognized as important regulators for tumor progression and therapy. Because metabolism genes are involved in tumor initiation and progression, little is known about the metabolic genomic profiles in low-grade glioma (LGG). Here, we applied bioinformatics analysis to determine the metabolic characteristics of patients with LGG from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). We also performed the ConsensusClusterPlus, the CIBERSORT algorithm, the Estimate software, the R package "GSVA," and TIDE to comprehensively describe and compare the characteristic difference between three metabolic subtypes. The R package WGCNA helped us to identify co-expression modules with associated metabolic subtypes. We found that LGG patients were classified into three subtypes based on 113 metabolic characteristics. MC1 patients had poor prognoses and MC3 patients obtained longer survival times. The different metabolic subtypes had different metabolic and immune characteristics, and may have different response patterns to immunotherapy. Based on the metabolic subtype, different patterns were exhibited that reflected the characteristics of each subtype. We also identified eight potential genetic markers associated with the characteristic index of metabolic subtypes. In conclusion, a comprehensive understanding of metabolism associated characteristics and classifications may improve clinical outcomes for LGG.

Enumeration of viable CD34+ cells in cord blood using a novel stem cell enumeration kit.

OBJECTIVE: To assess the detection performance of the hematopoietic stem cell enumeration kit developed by BD Biosciences. METHODS: Cord blood samples were prepared using a hematopoietic stem cell enumeration kit developed by BD Biosciences and Stem-Kit reagents from Beckman Coulter. CD34+ cells were enumerated using a BD FACSCanto instrument and FACSDiva software. RESULTS: A total of 519 samples were analyzed in this study. The hematopoietic stem cell enumeration kit developed by BD Biosciences yielded absolute counts of CD34-positive cells that were on average 8.7% lower than Beckman Coulter Stem-Kit reagents (range: -5.7% to-14.7%). The BD Biosciences kit yielded relative counts that were on average 9.9% higher compared with Beckman Coulter Stem-Kit reagents (range: -2.1% to +13.8%). The intraclass correlation coefficients for absolute and relative counts of CD34-positive cells were 0.9967 (95% confidence interval [CI]: 0.9961-0.9972) and 0.9512 (95% CI: 0.9423-0.9587) for the BD Biosciences and Beckman Coulter kits, respectively. CONCLUSIONS: The hematopoietic stem cell enumeration kit developed by BD Biosciences can be used to enumerate CD34-positive stem cells from cord blood samples.

Establishment of the reference intervals of lymphocyte subsets for healthy Chinese Han adults and its influencing factors.

BACKGROUND: Cellular immune monitoring is becoming more critical in the clinic, but its application has not yet become sufficiently widespread. One reason may be the different reference intervals among clinical laboratories due to several factors. Percentage and number of lymphocyte subsets are standard indicators of cellular immune detection. The present study aimed to establish standardized reference intervals of lymphocyte subsets in the healthy Chinese Han adult population and examine such influencing factors as age, gender, region, and measurement instruments. METHODS: A total of 496 healthy Chinese Han people aged 18-59 years from 3 China Mainland regions (north, east, and south) were enrolled. The sample of each center was simultaneously examined by three flow cytometers (FACSCantoTMII, FACSLyricTM, and FACSCaliburTM). A single-platform flow cytometry-based absolute count technique was used to quantify the percentage and number of each lymphocyte subset. The flow cytometry results were analyzed by variance analysis and Z test to determine the influence of age, gender, and instruments on lymphocyte subsets. RESULTS: Multi-center, age-specific, and gender-specific reference intervals of healthy Chinese Han adults' lymphocyte subsets were established. There was no statistical difference in the results from the three flow cytometers. Gender affected the results of CD4+ (%) and the absolute count of CD3-CD16+CD56+, where CD4+ (%) was higher in women, and the absolute count of CD3-CD16+CD56+ was higher in men. Age mainly affected the CD4+/CD8+ ratio, which was statistically higher in groups aged over 40 years; the percentage and number of CD3-CD19+ were more elevated in age groups below 30 years; however, the difference was not statistically significant. CONCLUSIONS: This study established the reference intervals of lymphocyte subsets for healthy Chinese Han adult populations under the standardized methods. This study was the first nationwide study in China to use a flow cytometry-based single-platform method to establish the reference intervals of lymphocyte subsets of the healthy Chinese Han adult population. Gender and age were shown to influence the results of lymphocyte subsets.

Air pollutant emissions from the asphalt industry in Beijing, China.

Improving our understanding of air pollutant emissions from the asphalt industry is critical for the development and implementation of pollution control policies. In this study, the spatial distribution of potential maximum emissions of volatile organic compounds (VOCs) in the complete life cycle of asphalt mixtures, as well as the particulate matter (PM), asphalt fume, nonmethane hydrocarbons (NMHCs), VOCs, and benzoapyrene (BaP) emissions from typical processes (e.g., asphalt and concrete mixing stations, asphalt heating boilers, and asphalt storage tanks) in asphalt mixing plants, were determined in Beijing in 2017. The results indicated that the potential maximum emissions of VOCs in the complete life cycle of asphalt mixtures were 18,001 ton, with a large contribution from the districts of Daxing, Changping, and Tongzhou. The total emissions of PM, asphalt fume, NMHC, VOCs, and BaP from asphalt mixing plants were 3.1, 12.6, 3.1, 23.5, and 1.9 × 10-3 ton, respectively. The emissions of PM from asphalt and concrete mixing stations contributed the most to the total emissions. The asphalt storage tank was the dominant emission source of VOCs, accounting for 96.1% of the total VOCs emissions in asphalt mixing plants, followed by asphalt heating boilers. The districts of Daxing, Changping, and Shunyi were the dominant regions for the emissions of PM, asphalt fume, NMHC, and BaP, while the districts of Shunyi, Tongzhou, and Changping contributed the most emissions of VOCs.

Synergistic Catalysis by Single-Atom Catalysts and Redox Mediator to Improve Lithium-Oxygen Batteries Performance.

Lithium-oxygen (Li-O2 ) batteries with ultrahigh theoretical energy density have attracted widespread attention while there are still problems with high overpotential and poor cycle stability. Rational design and application of efficient catalysts to improve the performance of Li-O2 batteries is of significant importance. In this work, Co single atoms catalysts are successfully combined with redox mediator (lithium bromide [LiBr]) to synergistically catalyze electrochemical reactions in Li-O2 batteries. Single-atom cobalt anchored in porous N-doped hollow carbon spheres (CoSAs-NHCS) with high specific surface area and high catalytic activity are utilized as cathode material. However, the potential performances of batteries are difficult to adequately achieve with only CoSAs-NHCS, owing to the blocked electrochemical active sites covered by insulating solid-state discharge product Li2 O2 . Combined with LiBr as redox mediator, the enhanced OER catalytic effect extends throughout all formed Li2 O2 during discharge. Meantime, the certain adsorption effect of CoSAs-NHCS on Br2 and Br3 - can reduce the shuttle of RMox . The synergistic effect of Co single atoms and LiBr can not only promote more Li2 O2 decomposition but also reduce the shuttle effect by absorbing the oxidized redox mediator. Li-O2 batteries with Co single atoms and LiBr achieve ultralow overpotential of 0.69 V and longtime stable cyclability.

Microglia: A Potential Drug Target for Traumatic Axonal Injury.

Traumatic axonal injury (TAI) is a major cause of death and disability among patients with severe traumatic brain injury (TBI); however, no effective therapies have been developed to treat this disorder. Neuroinflammation accompanying microglial activation after TBI is likely to be an important factor in TAI. In this review, we summarize the current research in this field, and recent studies suggest that microglial activation plays an important role in TAI development. We discuss several drugs and therapies that may aid TAI recovery by modulating the microglial phenotype following TBI. Based on the findings of recent studies, we conclude that the promotion of active microglia to the M2 phenotype is a potential drug target for the treatment of TAI.

Foxo1-induced miR-92b down-regulation promotes blood-brain barrier damage after ischaemic stroke by targeting NOX4.

The blood-brain barrier (BBB) damage is a momentous pathological process of ischaemic stroke. NADPH oxidases 4 (NOX4) boosts BBB damage after ischaemic stroke and its expression can be influenced by microRNAs. This study aimed to probe into whether miR-92b influenced the BBB damage after ischaemic stroke by regulating NOX4 expression. Here, miR-92b expression was lessened in the ischaemic brains of rats and oxygen-glucose deprivation (OGD)-induced brain microvascular endothelial cells (BMECs). In middle cerebral artery occlusion (MCAo) rats, miR-92b overexpression relieved the ameliorated neurological function and protected the BBB integrity. In vitro model, miR-92b overexpression raised the viability and lessened the permeability of OGD-induced BMECs. miR-92b targeted NOX4 and regulated the viability and permeability of OGD-induced BMECs by negatively modulating NOX4 expression. The transcription factor Foxo1 bound to the miR-92b promoter and restrained its expression. Foxo1 expression was induced by OGD-induction and its knockdown abolished the effects of OGD on miR-92b and NOX4 expressions, cell viability and permeability of BMECs. In general, our findings expounded that Foxo1-induced lessening miR-92b boosted BBB damage after ischaemic stroke by raising NOX4 expression.