Light-Quality-Adapted Carotenoid Photoprotection in the Photosystem of Roseiflexus castenholzii.

The photosystem of filamentous anoxygenic phototroph Roseiflexus (Rfl.) castenholzii comprises a light-harvesting (LH) complex encircling a reaction center (RC), which intensely absorbs blue-green light by carotenoid (Car) and near-infrared light by bacteriochlorophyll (BChl). To explore the influence of light quality (color) on the photosynthetic activity, we compared the pigment compositions and triplet excitation dynamics of the LH-RCs from Rfl. castenholzii was adapted to blue-green light (bg-LH-RC) and to near-infrared light (nir-LH-RC). Both LH-RCs bind γ-carotene derivatives; however, compared to that of nir-LH-RC (12%), bg-LH-RC contains substantially higher keto-γ-carotene content (43%) and shows considerably faster BChl-to-Car triplet excitation transfer (10.9 ns vs 15.0 ns). For bg-LH-RC, but not nir-LH-RC, selective photoexcitation of Car and the 800 nm-absorbing BChl led to Car-to-Car triplet transfer and BChl-Car singlet fission reactions, respectively. The unique excitation dynamics of bg-LH-RC enhances its photoprotection, which is crucial for the survival of aquatic anoxygenic phototrophs from photooxidative stress.

Dynamic mechanisms of exercise to improve body satisfaction: Perceived or actual fat loss?

We examined the dynamic mechanisms of aerobic training (AT) and strength training (ST) to improve body satisfaction. Sixty-six participants were randomised to either the AT or ST condition and completed an 8-week intervention. Participants completed 3 weekly, 30-minute sessions of moderate intensity AT (65-75% VO2 max) or ST (65-75% 1-RM). The energy consumption of each session was approximately equivalent under both conditions. Body satisfaction, body composition, perceived fitness and exercise self-efficacy were measured at baseline and biweekly during the intervention. Exercise improved individuals' body satisfaction (p < .05). When the energy expenditures of AT and ST were equal, there was no difference in body satisfaction improvement. There were dynamic mechanisms underlying the effects of exercise on body satisfaction. Specifically, perceived fitness influenced body satisfaction improvements during the early stages of the exercise program, while changes in body composition influenced body satisfaction toward the end of the exercise program. There were sex differences in the mechanisms underlying body satisfaction. For women, perceived fat was more important in the early intervention period; for men, actual body fat was more valuable in the late intervention period. An effective strategy to improve body satisfaction is to initially target perceived fitness before focusing on changing body composition.

You don't know why you (don't) exercise: The relationship between automatic processes and physical activity (or sedentary behavior): A meta-analysis.

OBJECTIVES: This meta-analysis aimed to examine the relationship between automatic processes and behavior as well as their moderators. METHODS: There were 126 effect sizes (Fisher's Z) extracted from 55 independent research studies involving 10,432 participants. Meta-analyses were conducted using Comprehensive Meta-Analysis Version 3.3. Univariate meta-regression models were used to analyze underlying moderators. RESULTS: Meta-analysis after correction found that automatic processes could significantly and positively predict behavior, but the effect size was small (Fisher's Z = 0.057, p < 0.001, 95% CI [0.043, 0.070]). CONCLUSIONS: Different components of automatic processes, task reliability, and study design moderated the relationship between automatic processes and behavior. Future research could explore automatic measures at a neurophysiological level or use population-matched stimuli for specific populations to improve measure validity. In addition, future research should accumulate evidence on how to reduce sedentary behavior.

To run or not to run? Differences in implicit attitudes towards running: An EEG study.

OBJECTIVE: To understand the reasons for individuals do or do not exercise, we examined differences in implicit (affective and instrumental) attitudes between runners and non-runners. METHODS: In conjunction with electroencephalography (EEG) technology, 31 participants completed the affective and instrumental implicit associations test (IAT). RESULTS: Behavioural results showed that runners had more positive implicit (affective and instrumental) attitudes than non-runners. EEG results further explained the underlying mechanisms for the differences, namely that runners had higher cortical functional connectivity in the compatible condition than in the incompatible condition, while non-runners had the opposite results. CONCLUSIONS: Higher levels of neural processing efficiency were required for runners to perceive affective expectations towards running. Furthermore, ERP indicators (N1 amplitudes of incompatible tasks) can be used as valid criteria for potentially predicting exercise. This contributed to understanding why individuals do or do not exercise. Further research should focus on the effects of implicit attitudes towards exercise.

Is approaching sedentary behaviour or physical activity a reward? An EEG study.

OBJECTIVE: To understand why individuals (do not) exercise, our study examined differences in approach and avoidance tendencies towards physical activity and sedentary behaviours among runners and non-runners, especially at the neural level. METHODS: Using electroencephalography (EEG), 31 participants completed an approach-avoidance task. RESULTS: We found that at the behavioural level, non-runners were faster to approach sedentary behaviour relative to runners. However, at the neural level, they both had a tendency to avoid physical activity. Specifically, avoiding physical activity had less conflict monitoring (smaller N1), required more cognitive processes (larger P3), and was more neurologically efficient (higher alpha coherence). CONCLUSIONS: These results supported the theory of effort minimization in physical activity (TEMPA), with both runners and non-runners regarding sedentary behaviour as a reward. DATA AVAILABILITY STATEMENT: The authors confirm that the data supporting the findings of this study are available within the article [and/or] its supplementary materials.

Can placebo and nocebo affect post-exercise executive function?

This study examined the placebo and nocebo effects of conditioning and induced expectations on executive function after acute aerobic exercise. The results showed that the benefits of exercise on executive function were influenced by both conditioning and induced expectations. Further, positive conditioning or expectations enhanced cognitive benefits, negative conditioning or expectations reduced cognitive benefits, but induced expectations on executive function were not moderated by conditioning. This study revealed and quantitively estimated the placebo and nocebo effects in improving executive function after acute aerobic exercise, providing evidence to advance the understanding of the cognitive benefits of exercise.

Can acute exercise be more pleasant? Using audiovisual stimuli: A meta-analysis.

This meta-analytic study aimed to examine the effects of audiovisual stimuli on affective responses during and after exercise and their moderators. A total of 296 effect sizes (Hedge's g) were extracted from 46 independent studies covering 1292 participants. Meta-analysis was performed using Comprehensive Meta-Analysis Version 3.3, and potential moderating variables were analysed using univariate meta-regression models. Audiovisual stimuli increased affective valence during (g = 0.793, 95% CI [0.666, 0.920]) and after exercise (g = 0.792, 95% CI [0.567, 1.016]), and arousal during (g = 0.920, 95% CI [0.742 1.097]) and after exercise (g = 0.666, 95% CI [0.390, 0.962]). There may be publication bias in the meta-analysis, but the main findings are still valid. The type of audiovisual stimuli (audio-video > audio or video), exercise habits (active > not reported), and exercise intensities (self-selected > imposed) moderated the effects. In conclusion, the application of audiovisual stimuli during exercise can elicit positive affective responses. These results provide a viable intervention strategy for exercise and health practitioners to reduce the number of physically inactive individuals and improve exercise compliance and adherence.

Expectations Come True: The Placebo Effect of Exercise on Affective Responses.

Objective: This study investigated the placebo and nocebo effects of habitual and induced expectations. Methods: In Study 1, 95 participants (Mage = 19.65 ± 2.21 years, MBMI = 21.94 ± 2.55) were grouped according to habitual expectations (positive, neutral, or negative) and completed a 30-min moderate-intensity aerobic exercise, and their affective response, rating of perceived exertion (RPE), and heart rate variability (HRV) were measured before, during, and after the exercise. In Study 2, the participants from Study 1 were grouped according to induced expectations (control, positive, or negative) and completed a 30-min moderate-intensity aerobic exercise. Affective response, RPE, and HRV were measured before, during, and after exercise. Results: In Study 1, positive habitual expectations increased affective response during and after exercise [F(2, 92) = 2.959, p = .057, ηp2 = .060], and negative habitual expectations increased RPE during exercise [F(2, 92) = 5.174, p = .007, ηp2 = .101]. In Study 2, positive induced expectation increased affective response during [F(2, 86) = 5.492, p = .006, ηp2 = .113] and after exercise [F(2, 86) = 6.096, p = .003, ηp2 = .124] and was not affected by habitual expectation. Conclusion: The affective response during and after exercise is influenced by habitual and induced expectations. Positive expectations enhance affective benefits, while negative expectations reduce affective benefits.

The Alleviation of Dextran Sulfate Sodium (DSS)-Induced Colitis Correlate with the logP Values of Food-Derived Electrophilic Compounds.

Food-derived electrophilic compounds (FECs) are small molecules with electrophilic groups with potential cytoprotective effects. This study investigated the differential effects of six prevalent FECs on colitis in dextran sodium sulfate (DSS)-induced mice and the underlying relationship with molecular characteristics. Fumaric acid (FMA), isoliquiritigenin (ISO), cinnamaldehyde (CA), ferulic acid (FA), sulforaphane (SFN), and chlorogenic acid (CGA) exhibited varying improvements in colitis on clinical signs, colonic histopathology, inflammatory and oxidative indicators, and Nrf2 pathway in a sequence of SFN, ISO > FA, CA > FMA, CGA. Representative molecular characteristics of the "penetration-affinity−covalent binding" procedure, logP value, Keap1 affinity energy, and electrophilic index of FECs were theoretically calculated, among which logP value revealed a strong correlation with colitis improvements, which was related to the expression of Nrf2 and its downstream proteins. Above all, SFN and ISO possessed high logP values and effectively improving DSS-induced colitis by activating the Keap1−Nrf2 pathway to alleviate oxidative stress and inflammatory responses.

A Study on the Dynamic Tunning Range of CVD Graphene at Microwave Frequency: Determination, Prediction and Application.

In recent years, graphene has shown great application prospects in tunable microwave devices due to its tunable conductivity. However, the electromagnetic (EM) properties of graphene, especially the dynamic tunning characteristics, are largely dependent on experimental results, and thus are unable to be effectively predicted according to growth parameters, which causes great difficulties in the design of graphene-based tunable microwave devices. In this work, we systematically explored the impact of chemical vapor deposition (CVD) parameters on the dynamic tunning range of graphene. Firstly, through improving the existing waveguide method, the dynamic tunning range of graphene can be measured more accurately. Secondly, a direct mathematical model between growth parameters and the tunning range of graphene is established. Through this, one can easily obtain needed growth parameters for the desired tunning range of graphene. As a verification, a frequency tunable absorber prototype is designed and tested. The good agreement between simulation and experimental results shows the reliability of our mathematic model in the rapid design of graphene-based tunable microwave devices.

Stretchable and self-healable spoof plasmonic meta-waveguide for wearable wireless communication system.

Microwave transmission lines in wearable systems are easily damaged after frequent mechanical deformation, posing a severe threat to wireless communication. Here, we report a new strategy to achieve stretchable microwave transmission lines with superior reliability and durability by integrating a self-healable elastomer with serpentine-geometry plasmonic meta-waveguide to support the spoof surface plasmon polariton (SSPP). After mechanical damage, the self-healable elastomer can autonomously repair itself to maintain the electromagnetic performance and mechanical strength. Meanwhile, the specially designed SSPP structure exhibits excellent stability and damage resistance. Even if the self-healing process has not been completed or the eventual repair effect is not ideal, the spoof plasmonic meta-waveguide can still maintain reliable performance. Self-healing material enhances strength and durability, while the SSPP improves stability and gives more tolerance to the self-healing process. Our design coordinates the structural design with material synthesis to maximize the advantages of the SSPP and self-healing material, significantly improving the reliability and durability of stretchable microwave transmission lines. We also perform communication quality experiments to demonstrate the potential of the proposed meta-waveguide as interconnects in future body area network systems.

Electroacupuncture Attenuates Immune-Inflammatory Response in Hippocampus of Rats with Vascular Dementia by Inhibiting TLR4/MyD88 Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate whether electroacupuncture (EA) alleviates cognitive impairment by suppressing the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway, which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia (VaD).@*METHODS@#The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table, including sham, four-vessel occlusion (4-VO), 4-VO+EA, 4-VO+non-EA, sham+EA, 4-VO+lipopolysaccharide (LPS), 4-VO+LPS+EA, and 4-VO+TAK-242 groups. The VaD model was established by the 4-VO method. Seven days later, rats were treated with EA at 5 acupoints of Baihui (DV 20), Danzhong (RN 17), Geshu (BL 17), Qihai (RN 6) and Sanyinjiao (SP 6), once per day for 3 consecutive weeks. Lymphocyte subsets, lymphocyte transformation rates, and inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α) were measured to assess immune function and inflammation in VaD rats. Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus. The levels of TLR4, MyD88, IL-6, and TNF-α were detected after EA treatment. TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA.@*RESULTS@#Compared with the 4-VO group, EA notably improved immune function of rats in the 4-VO+EA group, inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats, reduced the expressions of serum IL-6 and TNF-α (all P0.05).@*CONCLUSIONS@#EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway. Thus, EA may be a promising alternative therapy for the treatment of VaD.

Substance P Mediates Estrogen Modulation Proinflammatory Cytokines Release in Intervertebral Disc.

Intervertebral disc degeneration (IDD) is a main contributor to low back pain. A close relationship exists between inflammation and pain. Estrogen can affect inflammation and may play a crucial role in IDD and pain. Substance P (SP) can also regulate the expression of pro-inflammatory cytokines in intervertebral disc (IVD). This study aimed to investigate the potential role of SP in estrogen regulation of IDD. Nine-week-old C57BL/6 female mice were divided into four groups as follows: sham surgery (sham), ovariectomy (OVX), ovariectomy plus estrogen replacement therapy (ERT) group (OVX+E2), and ovariectomy, ERT plus neurokinin 1 receptor (NK1R) agonist (OVX+E2+G). Serum E2, body, and uterus weight were recorded. Immunohistochemistry study and quantitative real-time PCR were used for SP, NK1R, IL-1ß, IL-6, and TNF-α examination and comparison in IVD at protein and gene levels. After OVX, the gene and protein expression of TNF-α, IL-1ß, IL-6, SP, and NK1R in NP cells significantly increased compared with the sham group. ERT can reverse these impacts. ERT plays anti-inflammatory and anti-hyperalgesic roles in IDD of OVX mice. The estrogen-induced changes of the pro-inflammatory cytokines, TNF-α, IL-1ß, and IL-6, are significantly inhibited by NK1R agonists. SP may be a mediator of estrogen regulating pro-inflammatory factors in IDD. Estrogen may affect IVD inflammation through two ways: one is to directly affect the level of pro-inflammatory cytokines and the other is by means of modulation of SP.

Factors associated with outcomes of septic shock patients receiving high dose noradrenaline according to three primary infection sites.

OBJECTIVE: To identify factors associated with outcome of septic shock patients receiving high dose noradrenaline according to three primary infection sites. METHODS: This retrospective study was based on data from a publicly available ICU database (Medical Information Mart for Intensive Care [MIMIC] III. Septic shock patients receiving high dose (≥1 µg/kg per min) noradrenaline and ≥18 years were identified and their characteristics and outcomes were compared according to three primary infection sites (abdominal, respiratory and urinary tract). RESULTS: 154 septic shock patients who received high doses of noradrenaline were identified; (89 [58%] had a respiratory infection, 41 [27%] an abdominal infection and 24 [16%] a urinary infection). There were no differences among the three infection groups in duration/maximum dosage of noradrenaline, length of stay in the ICU/hospital, do not resuscitate (DNR) rates, hypertension and adequate antimicrobial therapy. Patients with urinary infections had a lower risk of death at 28-days compared with those with abdominal or respiratory infections. CONCLUSIONS: The prognosis for septic shock patients receiving high dose noradrenaline is poor. Patients with abdominal or respiratory infections are at higher risk of death compared with those with urinary infections.

Utilization of echocardiography during septic shock was associated with a decreased 28-day mortality: a propensity score-matched analysis of the MIMIC-III database.

BACKGROUND: Hemodynamic management is of paramount importance in patients with septic shock. Echocardiography has been increasingly used in assessing volume status and cardiac function. However, whether the utilization of echocardiography has an impact on prognosis is unknown. Thus, we intended to explore its effect on the outcomes of patients with septic shock. METHODS: The study was based on the Medical Information Mart for Intensive Care (MIMIC) III database. Septic shock patients were divided into two groups according to the usage of echocardiography during the onset of septic shock. The primary outcome was 28-day mortality. Secondary outcomes included the usage of inotropes, ventilation-free and norepinephrine-free time, and fluids input. Propensity-score matching was used to reduce the imbalance. RESULTS: Among 3,291 eligible patients, 1,289 patients who underwent echocardiography (Echo), and 1,289 who did not receive the Echo, had similar propensity scores and were included in the analyses. After matching, the Echo group had a significantly lower 28-day mortality (33.2% vs. 37.7%, P=0.019). More patients in the Echo group received pulmonary artery catheter (PAC) (4.2% vs. 0.2%, P<0.001) and inotropes (17.8% vs. 7.1%, P<0.001). In the survival analysis, Echo utilization was associated with improved 28-day mortality [hazard ratio (HR): 0.83; 95% confidence interval (CI), 0.73-0.95, P=0.005]. A reduced likelihood of 28-day mortality in patients with Echo vs. those without Echo was maintained either when excluding patients receiving multiple echocardiography scans (HR, 0.82; 95% CI, 0.72-0.94; P=0.004) or when excluding patients undergoing PAC or pulse index continuous cardiac output (PiCCO) (HR, 0.87; 95% CI, 0.76-0.99; P=0.034). CONCLUSIONS: Utilization of echocardiography was associated with improved 28-day outcomes in patients with septic shock.

Acute Hypervolemic Infusion Can Improve Splanchnic Perfusion in Elderly Patients During Laparoscopic Colorectal Surgery.

BACKGROUND There is no adequate evidence on how the long duration of laparoscopic surgery affects splanchnic perfusion in elderly patients or the efficacy of acute hypervolemic fluid infusion (AHFI) during the induction of anesthesia. Our aim was to observe the effects of AHFI during the induction of general anesthesia on splanchnic perfusion. MATERIAL AND METHODS Seventy elderly patients receiving laparoscopic colorectal surgery were randomly divided into three groups: lactated Ringer's solution group (group R), succinylated gelatin group (group G), and hypertonic sodium chloride hydroxyethyl starch 40 injection group (group H). Thirty minutes after the induction of general anesthesia, patients received an infusion of target dose of these three solutions. Corresponding hemodynamic parameters, arterial blood gas analysis, and gastric mucosal carbon dioxide tension were monitored in sequences. RESULTS In all three groups, gastric-arterial partial CO2 pressure gaps (Pg-aCO2) were decreased at several beginning stages and then gradually increased, Pg-aCO2 also varied between groups due to certain time points. The pH values of gastric mucosa (pHi) decreased gradually after the induction of pneumoperitoneum in the three groups. CONCLUSIONS The AHFI of succinylated gelatin (12 ml/kg) during the induction of anesthesia can improve splanchnic perfusion in elderly patients undergoing laparoscopic surgery for colorectal cancer and maintain good splanchnic perfusion even after a long period of pneumoperitoneum (60 minutes). AHFI can improve splanchnic perfusion in elderly patients undergoing laparoscopic colorectal surgery.

Different doses of sevoflurane facilitate and impair learning and memory function through activation of the ERK pathway and synthesis of ARC protein in the rat hippocampus.

BACKGROUND: Sevoflurane has been shown to stimulate or depress memory in adult rats; however, the cellular mechanism of this bidirectional effect has not been fully investigated. METHODS: We used an intra-hippocampal microinfusion of U0126 to suppress ERK activation. Male SD rats were randomly assigned to four groups: Sham, 0.11%SEV, 0.3%SEV and 0.3%+U0126. They received bilateral injections of U0126 or saline. Rats were anesthetized, and Inhibitory Avoidance (IA) training was performed immediately after anesthesia. The memory retention latency was observed 24 h later. In another experiment, the hippocampus was removed 45 min after IA training to assess ARC expression, the synapsin 1 protein levels and the phosphorylation level of ERK. RESULTS: Treatment with 0.11%SEV led to rapid phosphorylation of ERK, while 0.3%SEV inhibited phosphorylation; the latter change was reversed by the microinfusion of U0126 in the hippocampus. The memory latency result had similar tendencies. The local infusion of U0126 abolished the 0.3%SEV-induced memory impairment and ERK inhibition. Selective upregulations of ARC and synapsin 1 proteins were observed in the 0.3%SEV group compared with the 0.11%SEV group. CONCLUSIONS: The results indicate that different doses of sevoflurane trigger synaptic plasticity-related cytoskeleton proteins through the ERK signaling pathway. This novel modulation by inhalational agents may help to reduce their side-effects on memory function.

Effects of Low Bone Mineral Status on Biomechanical Characteristics in Idiopathic Scoliotic Spinal Deformity.

BACKGROUND: Low bone mass in patients with adolescent idiopathic scoliosis has been well reported. Poor bone quality was regarded as a new and unique prognostic factor in aggravating curve progression. However, the potential biomechanical correlation between them remains unclear. METHODS: Three-dimensional finite element models of idiopathic scoliotic spine with different bone mineral status were created for axial loading simulation. An axial load of 3 different body weights was applied on different bone mineral mass models. The mechanical responses of the vertebral cortical and cancellous bone, facet joints, end plate, and intervertebral disc were analyzed. RESULTS: Accompanied with the low bone mineral status, thoracic scoliosis produced asymmetric and higher stress in the cortical bone, lumbar facet joints, and end plate at the concave side of the thoracic structure curve. Stress increased in the disc at the apex of the scoliosis, whereas it mildly decreased in the L4-5 and L5-S1 disc. Body weight gain increased the stress in scoliotic spine structures in all bone mineral statues. CONCLUSIONS: Biomechanical simulations indicated that low bone mineral mass might aggravate curve progression and induce more serious lumbar compensatory scoliosis in patients with adolescent idiopathic scoliosis. Weight gain was also a risk factor for curve progression.

Estrogen receptors involvement in intervertebral discogenic pain of the elderly women: colocalization and correlation with the expression of Substance P in nucleus pulposus.

Estrogenic modulation of pain is an exceedingly complex phenomenon. However, whether estrogen is involved in discogenic low back pain still remains unclear. Here, immunoreactivity staining technique was used to examine the expression level of the estrogen receptors (ERα and ERß) and a pain related neuropeptide, Substance P in the lumbar intervertebral discs to analyze the relationship between the ERs and Substance P. Nucleus pulposus tissues of 23 elderly female patients were harvested during spinal surgeries and made to detect the immunoreactivity staining of ERα, ERß and Substance P. The colocalization and intensities of ERs and Substance P were explored and evaluated respectively. The correlations between changes of ERα, ERß and Substance P were also assessed.Our results revealed that Substance P colocalized with ERα and ERß both in cytoplasm and nucleus of the nucleus pulposus cells. HSCORE analysis indicated that Substance P negatively correlated with both ERα and ERß expression. Collectively, the crosstalk between ERs and Substance P might exist in the disc tissue. Estrogen-dependent pain mechanism might partly be mediated through ERs and Substance P in the nucleus pulposus of the elderly females. Estrogen and its receptors might be drug targets in discogenic low back pain diseases.

Photocontrolled extraction of uric acid from biological samples based on photoresponsive surface molecularly imprinted polymer microspheres.

We aim to develop novel photoresponsive surface molecularly imprinted polymer (SIMP) microspheres, an SiO2 -SIMP, for the photocontrolled extraction of uric acid from biological samples. The SiO2 -SMIP was prepared on silica microspheres by surface polymerization and characterized by using scanning electron microscopy, transmission electron microscopy, FTIR spectroscopy, thermogravimetric analysis, nitrogen adsorption-desorption analysis, and UV-visible spectroscopy. The SiO2 -SMIP microspheres showed a photocontrolled uptake and release of uric acid in NaH2 PO4 buffer upon alternate irradiation at 365 and 440 nm. The SiO2 -SMIP microspheres were able to photocontrollably extract uric acid from complicated biological samples for concentration analysis with no significant interference encountered and it exhibited very good recognition ability and fast binding kinetics toward uric acid.