Causal association between tea consumption and head and neck cancer: a Mendelian randomization study.

Although evidence supports an observational association between tea consumption and susceptibility to head and neck cancer, the causal nature of this association remains unclear. We performed a two-sample Mendelian randomization (MR) analysis to determine the causal effects of tea consumption on head and neck cancer. We employed a fixed-effects inverse variance-weighted model for the MR analysis. Genome-wide association study (GWAS) summary data for tea consumption were obtained from the UK Biobank Consortium, and GWAS data for head and neck cancer were derived from two data sources and were used as the outcomes. Our MR analysis revealed limited evidence for a causal relationship between various types of tea intake and head and neck cancer. After adjustment for smoking and alcohol consumption, there was no causal relationship between tea consumption and head and neck cancer. Further experimental studies are required to confirm its potential role in these malignancies.

Lycopene-loaded emulsions stabilized by whey protein covalently modified with pectin or/and chlorogenic acid: Enhanced physicochemical stability and reduced bio-accessibility.

Lycopene-loaded emulsions were formulated with whey protein isolate (WPI) covalently modified with high methoxylated pectin (HMP) or/and chlorogenic acid (CA) prepared by dry heating or/and alkali grafting. Covalent WPI products were confirmed by SDS-PAGE and degree of graft/CA binding equivalent values. The α-helix and ß-sheet percentage, surface hydrophobicity and fluorescence intensity of WPI decreased significantly (p < 0.05) upon binding. Both binary and ternary complexes enhanced the stability of the emulsions, and lycopene retained more after UV irradiation, thermal treatment, storage, compared with emulsions stabilized by WPI, with the best protection by both ternary complexes. In vitro simulated digestion results showed that free fatty acids were released in the order of WPI > WPI-HMP > WPI-CA > WPI-HMP-CA ≈ WPI-CA-HMP. Bio-accessibility analysis showed the same trend as the fatty acid release rate. These results may provide a theoretical basis for applications of conjugating protein with polysaccharide or/and polyphenol emulsions.

Hydrogeochemical Evaluation of Groundwater Quality Parameters for Ogallala Aquifer in the Southern High Plains Region, USA.

The purposes of this study are to analyze the groundwater quality of the Ogallala Aquifer and evaluate the hydrological characteristics in the southern High Plains region of the Permian Basin, Texas. Levels of chloride, fluoride, nitrate, selenium, pH, and total dissolved solids (TDS) were analyzed for the period 1990-2016. Data concerning a total of 133 wells were collected from the Texas Water Development Board (TWDB), which is an open database provided by the US government. The average levels of contaminants were compared to their respective Maximum Contaminant Levels (MCL) stipulated by the Environmental Protection Agency (EPA). The study area experienced high concentrations of most parameters including chloride, fluoride, nitrate, selenium, and TDS, within the contaminants' respective MCLs. Borden and Dawson counties experienced the highest overall amounts of groundwater pollutants. Possible sources of each contaminant are discussed, with oil and gas activities, agricultural practices, and other human actions impacting the conditions. This research provides important information about groundwater quality of the Ogallala Aquifer and contributes to understanding the response to development in the Permian Basin, Texas.

Site-Specific Conjugation of a Selenopolypeptide to Alpha-1-antitrypsin Enhances Oxidation Resistance and Pharmacological Properties.

Human alpha-1-antitrypsin (A1AT), a native serine-protease inhibitor that protects tissue damage from excessive protease activities, is used as an augmentation therapy to treat A1AT-deficienct patients. However, A1AT is sensitive to oxidation-mediated deactivation and has a short circulating half-life. Currently, there is no method that can effectively protect therapeutic proteins from oxidative damage in vivo. Here we developed a novel biocompatible selenopolypeptide and site-specifically conjugated it with A1AT. The conjugated A1AT fully retained its inhibitory activity on neutrophil elastase, enhanced oxidation resistance, extended the serum half-life, and afforded long-lasting protective efficacy in a mouse model of acute lung injury. These results demonstrated that conjugating A1AT with the designed selenopolymer is a viable strategy to improve its pharmacological properties, which could potentially further be applied to a variety of oxidation sensitive biotherapeutics.

Solution-Processed All-inorganic Planar Heterojunction Solar Cells by Employing In Situ Grown Interfacial Layer with Dual Functions: Complementary Absorption and Selective Extraction of Photogenerated Holes.

Photovoltaic conversion of renewable solar energy into electricity for sustainable energy production requires efficient, stable, and low-cost solar cells. Developing solution-processed all-inorganic solar cells is a practical scenario in virtue of the high charge mobility and good stability of inorganic semiconductors. Here, for the first time, we present a solution-processed all-inorganic planar heterojunction solar cell based on the nanoparticle film of copper indium sulfide (CuInS2) by using an antimony trisulfide (Sb2S3) nanoparticle film as an interfacial layer between the CuInS2 photon-harvesting layer and cathode. All of the component layers in the solar cell are in a superstrate architecture and sequentially in situ grown on a transparent conducting glass acting as anode by solution-processing methods. The dependences of device performance on the thickness of Sb2S3 film and the reduction of hole-trapping centers in the Sb2S3 film by thioacetamide treatment are investigated. The optimized all-inorganic device exhibits the best power conversion efficiency of 4.85% under AM 1.5G illumination and an excellent thermal stability. It is found that the Sb2S3 interfacial layer sandwiched between the CuInS2 photon-harvesting layer and counter-electrode has dual functions, that is, to provide complementary absorption after CuInS2 attenuation and to act as an effective hole-transporting layer to selectively extract photogenerated holes for effective charge collection efficiency.

The effectiveness and safety of Tai Chi for patients with essential hypertension: study protocol for an open-label single-center randomized controlled trial.

BACKGROUND: Evidence showed that Tai Chi may have beneficial effects among hypertensive individuals, although the results are not convincing. We aim to conduct a high-quality clinical trial with 24-h BP measurement to provide robust evidence of Tai Chi for essential hypertension. METHODS: This is an open-label single-center randomized controlled trial with 3 parallel arms. We will compare Tai Chi with walking and waiting-list control. We will recruit 234 hypertensive patients with mild to moderate essential hypertension and randomly assign them to 3 different groups. Participants in Tai Chi group will receive a group-format Yang style 24-form Tai Chi exercise program, 3 sessions per week for 12 weeks. The walking group will be asked to walk, 3 sessions per week for 12 weeks. The waiting-list group will not receive any interventions and/or exercise training. The primary outcome is the change in average 24-h systolic blood pressure (SBP) between baseline and 12 weeks after randomization. The secondary outcomes include 24-h Diastolic Blood Pressure (DBP), average SBP and average DBP during the daytime and night-time, blood pressure (BP) variability, SBP load and DBP load, circadian rhythm of BP, and morning BP surge, endothelial functional indicators, home measured BP, quality of life, adverse events and so on. DISCUSSION: We expect findings of this trial will provide important insight into application of Tai Chi as an effective and acceptable method for hypertensive patients. Successful completion of this proposed study will also contribute to promotion of Tai Chi in the community in the future. TRIAL REGISTRATION: Clinicaltrials.gov registry: https://clinicaltrials.gov/ct2/show/NCT04267471 , date: February 12, 2020.

Identification of Aroma Composition and Key Odorants Contributing to Aroma Characteristics of White Teas.

The identification of aroma composition and key odorants contributing to aroma characteristics of white tea is urgently needed, owing to white tea's charming flavors and significant health benefits. In this study, a total of 238 volatile components were identified in the three subtypes of white teas using headspace solid-phase microextraction (HS-SPME) combined with comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOFMS). The multivariate statistical analysis demonstrated that the contents of 103 volatile compounds showed extremely significant differences, of which 44 compounds presented higher contents in Baihaoyinzhen and Baimudan, while the other 59 compounds exhibited higher contents in Shoumei. The sensory evaluation experiment carried out by gas chromatography-olfactometry/mass spectrometry (GC-O/MS) revealed 44 aroma-active compounds, of which 25 compounds were identified, including 9 alcohols, 6 aldehydes, 5 ketones, and 5 other compounds. These odorants mostly presented green, fresh, floral, fruity, or sweet odors. Multivariate analyses of chemical characterization and sensory evaluation results showed that high proportions of alcohols and aldehydes form the basis of green and fresh aroma characteristic of white teas, and phenylethyl alcohol, γ-Nonalactone, trans-ß-ionone, trans-linalool oxide (furanoid), α-ionone, and cis-3-hexenyl butyrate were considered as the key odorants accounting for the different aroma characteristics of the three subtypes of white tea. The results will contribute to in-depth understand chemical and sensory markers associated with different subtypes of white tea, and provide a solid foundation for tea aroma quality control and improvement.

Simultaneous Enantioselective Determination of Two New Isopropanol-Triazole Fungicides in Plant-Origin Foods Using Multiwalled Carbon Nanotubes in Reversed-Dispersive Solid-Phase Extraction and Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry.

A simple and sensitive enantiomeric analytical method was established for the determination of two new isopropanol-triazole fungicides mefentrifluconazole and ipfentrifluconazole in plant-origin foods using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The best enantioseparation of the four target stereoisomers was achieved on a Chiral MX(2)-RH column within 7 min by reversed-phase liquid chromatography, which is a significant improvement in the resolution of different chiral compounds under one set of conditions. A simple and effective pretreatment procedure was developed for the extraction and purification of the two target chiral fungicides using reversed-dispersive solid-phase extraction (r-DSPE) with multiwalled carbon nanotubes (MWCNTs). The influence of the type and amount of MWCNTs on the purification efficiencies and recoveries was evaluated. The mean recoveries for all four stereoisomers were in the range of 76.9-91.2%, with relative standard deviation (RSD) values below 7.2%. The limit of quantification (LOQ) of all stereoisomers of mefentrifluconazole and ipfentrifluconazole was 5 µg/kg for all tested matrixes. The results of the method validation and real samples analysis confirm that the established method is efficient and reliable for the enantiomeric determination of mefentrifluconazole and ipfentrifluconazole in plant-origin food samples.

Pharmacokinetics, tissue distribution and excretion study of trans-resveratrol-3-O-glucoside and its two metabolites in rats.

BACKGROUND: Trans-resveratrol-3-O-glucoside (TRG), isolated from the Chinese traditional herbal medicine Huzhang, has been shown to have a wide range of pharmacological benefits. PURPOSE: The aim of this study is to investigate the pharmacokinetics, tissue distribution and excretion of TRG and its metabolites, (TRN (trans-resveratrol-3-O-glucuronide) and TR (trans-resveratrol)), following a single intragastric (i.g.) administration of TRG in rats. STUDY DESIGN: To evaluate the pharmacokinetic properties of TRG, TRN and TR, groups of rats were administrated a single i.g. dose of either 75, 150 or 300 mg/kg TRG. The absolute bioavailability of TRG was estimated from the ratios of AUC0-∞ values for oral and intravenous administration. Tissue distributions of TRG, TRN and TR in rats were investigated following a single i.g. administration to four groups at 150 mg/kg dosage of TRG. For urinary, fecal and biliary excretion study, TRG, TRN and TR excretions were recovered from a group of rats administered a single i.g. dose of 150 mg/kg TRG. METHODS: The levels of TRG, TRN and TR in plasma, tissues, bile, urine and feces were measured by a rapid and sensitive LC-UV method. The precision was below 10.0%, and the accuracy was within ±9.9% for TRG, TRN and TR. RESULTS: The concentrations of TRN were markedly higher than those of TRG and TR in plasma, urine and bile. TRG, TRN and TR showed linear dynamics in dose range of 75-300 mg/kg TRG. TRG had poor absolute bioavailability in rats. The major distribution tissues of TRG, TRN, and TR in rats were in the digestive tract. TRG, TRN and TR were all eliminated from tissues quickly. TRG was mostly excreted via the renal route in the form of TRN, which accounted for 52.8% of the administered dose up to 72 h. CONCLUSION: Following a single i.g. administration to rats TRG was easily absorbed and rapidly converted to the metabolites TR and TRN. These metabolites were found to be mainly excreted by the kidneys.

Spatiotemporal variability of soil nutrients and the responses of growth during growth stages of winter wheat in northern China.

Studying soil nutrient variability and its effect on the growth and development of crops under a traditional tillage mode is the foundation for comprehensively implementing precision agriculture policies at the field scale and ensuring excellent crop management. In this paper, a 28.5 hm2 winter wheat field under the traditional cultivation model in Tianzhuang town of Huantai County was selected as the research area. The mesh point method was utilized for sampling (60×60 m), and the characteristics of soil available nitrogen (AN), available phosphorus (AP) and available potassium (AK) variations in the before sowing, reviving, jointing, and filling stages of winter wheat were analyzed using geostatistical and GIS methods. Moreover, Pearson correlation analysis was used to study the response of wheat growth and development to soil nutrient variations. As the growth stages progressed, 1) each nutrient showed the characteristics of low-high-low and moderate variability. The highest AN and AK contents were found at the reviving stage, while AP reached a turning point at the jointing stage. The order of variability of each nutrient was AN>AP>AK. 2) The nutrient variations first increased and then decreased and showed medium to strong spatial correlation. The three nutrients were strongly spatially correlated in the before sowing stage and moderately spatially correlated during the reviving stage. During the jointing and filling stages, AN had moderate spatial correlation, and AP and AK had strong spatial correlation. The spatial correlation of each nutrient was the weakest in the reviving stage, and the spatial correlation of AN was strongest in the before sowing stage, while the spatial correlations of AP and AK were strongest in the jointing stage. The spatial correlation of each soil nutrient decreased from the before sowing stage to the reviving stage and from the jointing stage to the filling stage, and the spatial correlation increased from the reviving stage to the jointing stage. 3) The soil nutrient content first increased and then decreased, and the grades of the nutrients gradually decreased. 4) The correlation between soil nutrients and wheat growth gradually increased. AN had the highest correlation with wheat growth, followed by AK and AP. The effect of soil nutrients on the growth of wheat at the reviving stage was greater than the effect of nutrients in the current stage. The growth of wheat at the jointing stage was mainly influenced by nutrients in the current stage, while the growth of wheat at the filling stage was influenced by the nutrient contents of both the previous and current stages. Thus, the date of fertilizer supplementation should be postponed properly. In this study, the soil nutrient dynamics and their influence on the growth of wheat during the winter wheat growth period under the traditional field model were well described, and these results could provide a theoretical basis for the precision management of soil nutrients in the northern winter wheat area where the planting environment and cultivation management are relatively uniform.

Cardiotoxicity of 5-fluorouracil and capecitabine in Chinese patients: a prospective study.

BACKGROUND: 5-Fluorouracil (5-FU) and capecitabine-associated cardiotoxicity ranging from asymptomatic electrocardiography (ECG) abnormalities to severe myocardial infarction has been reported in a number of studies, but such cardiotoxicity in Chinese patients with malignant diseases has not been investigated to date. In the present study, we aimed to prospectively evaluate the incidence rates and clinical manifestations of 5-FU- and capecitabine-associated cardiotoxicity in cancer patients recruited from multiple centers in China. METHODS: Among the 527 patients who completed the study, 196 received 5-FU-based chemotherapy and 331 received capecitabine-based chemotherapy as either first-line or adjuvant therapy. Adverse events were reported during the treatment and up to 28 days of follow-up. Outcome measures included ECG, myocardial enzymes, cardiac troponin, brain natriuretic peptide and echocardiography. Univariate analysis and logistic regression were performed for subgroup analysis and identification of significant independent variables that are associated with cardiotoxicity of both agents. RESULTS: In total, 161 of 527 patients (30.6%) experienced cardiotoxicity. The incidence rate of cardiotoxicity was 33.8% (112/331) in the capecitabine group, which was significantly higher than the rate of 25% (49/196) in the 5-FU group (P = 0.0042). 110/527 patients (20.9%) suffered arrhythmia, 105/527 (19.9%) developed ischemic changes, while only 20/527 patients (3.8%) presented heart failure and 6/527 patients (1.1%) had myocardial infarction. Pre-existing cardiac disease, hypertension, capecitabine-based chemotherapy and duration of treatment were identified as significant risk factors associated with cardiotoxicity. The odds ratio were 15.7 (prior history of cardiac disease versus no history), 1.86 (capecitabine versus 5-FU), 1.06 (5-8 versus 1-4 chemotherapy cycles) and 1.58 (hypertension versus no hypertension), respectively. CONCLUSIONS: Cardiotoxicity induced by fluoropyrimidines in the Chinese population may be underestimated in clinical practice. Close monitoring of patients is recommended, especially for those patients at high risk for cardiotoxicity. Possible risk factors are duration of treatment, capecitabine-based chemotherapy, pre-existing cardiac diseases and hypertension. Trial registration This study was initiated on January 22, 2014 and has been retrospectively registered with the registration number ChiCTR1800015434.

[Neurological protection effects of "paraplegia-triple-needling method" on rats with incomplete spinal cord injury].

OBJECTIVE: To observe the neurological protection effects of "paraplegia-triple-needling method" on rats with incomplete spinal cord injury (SCI), so as to make a preliminary exploration on its mechanism. METHODS: A total of 45 SD rats were randomly divided into a paraplegia-triple-needling method group (group A), a regular acupuncture group (group B) and a model group (group C), 15 rats in each one. The rats model of incomplete spinal cord injury was established by modified Allen's method. The acupoints of governor vessel and back-shu points next to the vertebras of upper end and lower end of injured segment as well as motor points in key muscle of lower extremities were treated with acupuncture in the group A; the acupoints of governor vessel and back-shu points next to the vertebras of upper end and lower end of injured segment as well as "Huantiao" (GB 30), "Housanli" (ST 36), "Yanglingquan" (GB 34) and "Genduan"(Extra) were treated with acupuncture in the group B; rats in the group C received no treatment after model establishment but grabbing and immobilization. The needles were retained for 15 min in the group A and group B, once a day for 14 times. 1 d, 7 d and 14 d after model establishment, Basso Beattie Bresnahan (BBB) scores were observed in each group; the morphologic change of injured spinal cord and expression of positive cells of calcitonin gene-related peptide (CGRP) were observed. Results (1) One day after SCI, there was no significant difference of BBB scores among three groups (P> 0. 05); 7 days and 14 days after SCI, BBB scores in the group A and group B were significantly superior to those in the group C (all P<0. 05), and the BBB scores in the group A were superior to those in the group B ( both P<0. 05). (2) There was expression of CGRP positive cells in all three groups, and that in the group A and group B was significantly higher than that in group C (both P<0. 05); 14 days after treatment, the expression in the group A was higher than that in the group B (P<0. 05). CONCLUSION: The "paraplegia-triple-needling method" could obviously! improve the motor function of rats with SCI, especially the expression of neuroprotective factor CGRP, which is likely to be one of the mechanisms of neurological protection effect.

Effects of amycenone on serum levels of tumor necrosis factor-α, interleukin-10, and depression-like behavior in mice after lipopolysaccharide administration.

Accumulating evidence suggests that inflammation plays a role in the pathophysiology of depression and that anti-inflammatory substances have antidepressant effects. Amycenone is obtained from extracts of the Yamabushitake (Hericium erinaceum). The purpose of this study is to examine whether amycenone shows anti-inflammatory and antidepressant effects in an inflammation-induced mouse model of depression. First, we examined the effects of amycenone on the serum levels of the pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), and the anti-inflammatory cytokine, interleukin-10 (IL-10), after intraperitoneal administration of the bacterial endotoxin lipopolysaccharide (LPS). Oral administration of amycenone (50, 100, or 200mg/kg) markedly blocked an increase in the serum TNF-α levels after a single administration of LPS (0.5mg/kg). Furthermore, amycenone (200mg/kg) markedly increased the serum IL-10 levels by a single administration of LPS (0.5mg/kg). Next, we examined the effects of amycenone on depression-like behaviors in the tail-suspension test (TST) and forced swimming test (FST). Pretreatment with amycenone (200mg/kg) significantly attenuated LPS (0.5mg/kg)-induced increase of the immobility time by the TST and FST, indicating antidepressant effects of amycenone. In addition, oral administration of paroxetine (30mg/kg) showed anti-inflammatory and antidepressant effects in the same model. These findings suggest that amycenone has antidepressant effects in LPS-induced inflammation model of depression. Therefore, amycenone could represent a potential supplement to prevent inflammation-related depression.

[Comparative study on effects of electroacupuncture stimulation of Shenmen (HT 7) and Taiyuan (LU 9) on P 300 of event-related potentials and brain electrical activity mapping in healthy young adults].

OBJECTIVE: To observe the effect difference of electroacupuncture (EA) stimulation of Shenmen (HT 7) and Taiyuan (LU 9) on P 300 of event-related potentials (ERPs) in volunteer subjects, so as to explore functional specificity of acupoints in processing cerebral information. METHODS: Sixty healthy volunteer college students were randomly and equally divided into Shenmen (HT 7) group and Taiyuan (LU 9) group (30 persons/group). EA (2 Hz, 1 mA) was applied to bilateral Shenmen (HT 7) and Taiyuan (LU 9) for 15 min. The ERPs were acquired by averaging EEG activity following Oddba II auditory tone-double stimuli and brain electrical activity mapping (BEAM) acquired by means of Scan 4.5 collection and analysis system. Data were calculated and analyzed with SPSS 17.0 for Windows. After testing, the subjects were inquired about the perception for acupuncture stimulation and other sensations or psychological activities. RESULTS: Following EA stimulation of both HT 7 and LU 9, the amplitude of P 300 in the ERPs were significantly decreased in comparison with pre-EA stimulation in the same one group (P < 0.01, P < 0.05). No significant changes were found in the latencies of P 300 after EA stimulation of both HT 7 and LU 9 (P > 0.05). But, EA of HT 7 had a slightly stronger effect in shortening P 300 latency. With regard to the potential intensity distribution of BEAM, there were some differences between HT 7 and LU 9 groups. The high potential responses for HT 7 were found mainly in the occipital lobe, and in the left parietal lobe and the right temporal lobe, whereas those for LU 9 were found to mainly disperse in the left occipital lobe and the parietal lobe. CONCLUSION: EA stimulation of HT 7 and LU 9 has a slight difference on lowering P 300 amplitude of ERPs, and may result in different distribution of the high potential responses in different lobes of the cerebral cortex in healthy subjects. The functional specificity of EA stimulation of different acupoints needs further study.

Behavioral modulation of neural encoding of click-trains in the primary and nonprimary auditory cortex of cats.

Neural representation of acoustic stimuli in the mammal auditory cortex (AC) has been extensively studied using anesthetized or awake nonbehaving animals. Recently, several studies have shown that active engagement in an auditory behavioral task can substantially change the neuron response properties compared with when animals were passively listening to the same sounds; however, these studies mainly investigated the effect of behavioral state on the primary auditory cortex and the reported effects were inconsistent. Here, we examined the single-unit spike activities in both the primary and nonprimary areas along the dorsal-to-ventral direction of the cat's AC, when the cat was actively discriminating click-trains at different repetition rates and when it was passively listening to the same stimuli. We found that the changes due to task engagement were heterogeneous in the primary AC; some neurons showed significant increases in driven firing rate, others showed decreases. But in the nonprimary AC, task engagement predominantly enhanced the neural responses, resulting in a substantial improvement of the neural discriminability of click-trains. Additionally, our results revealed that neural responses synchronizing to click-trains gradually decreased along the dorsal-to-ventral direction of cat AC, while nonsynchronizing responses remained less changed. The present study provides new insights into the hierarchical organization of AC along the dorsal-to-ventral direction and highlights the importance of using behavioral animals to investigate the later stages of cortical processing.

Cat's behavioral sensitivity and cortical spatiotemporal responses to the sweep direction of frequency-modulated tones.

Neural responses to frequency modulated (FM) sweeps have been well investigated in single-units using electrophysiological recording methods. However, rare psychophysical experiments were conducted to investigate behavioral discrimination of FM-sweeps in the same species used in physiological experiments. Also, the previous studies have not focused on how the population of cortical neurons works together to encode the direction of FM-sweeps. To investigate the relation between the behavioral perception of FM direction and the population coding, we examined the cat's capability to discriminate the upward and downward FM-sweeps and recorded the neural responses to the same stimuli from the primary auditory cortex (A1) in different awake cats. We found that cats showed high performance to detect the change of direction of FM-sweeps, which linearly swept between 0.1 and 16kHz in 40-160ms duration; however, the behavioral performance obviously deteriorated when the sweeps were shortened to 10-20ms. Physiological results indicated that the upward sweeps elicited a temporal sequence of responses among the A1 neurons, in which neurons tuning to low-frequencies responded earlier and those tuning to high-frequencies later, while the response sequence was reversed when A1 was driven by the downward sweeps. The rank-order of response latencies could provide a reliable discrimination of the FM direction, and the discrimination performance paralleled with the cat's behavioral performance. Our result suggests that the relative response timings in A1 contain enough information used by subsequent processing stages to make the decision of FM direction.

Improvement of heart function in postinfarct heart failure swine models after hepatocyte growth factor gene transfer: comparison of low-, medium- and high-dose groups.

Despite advances in surgical and reperfusion therapy, there is no effective therapy currently exists to prevent the progressive decline in cardiac function following myocardial infarction. Hepatocyte growth factor has potent angiogenic and anti-apoptotic activities. The aim of this study was to investigate the therapeutic effect and dose-effect relationship on postinfarction heart failure with different doses of adenovirus-mediated human hepatocyte growth factor (Ad(5)-HGF) transference in swine models. Totally twenty swine were randomly divided into four groups: (a) control group (null- Ad(5), 1 ml); (b) low-dose group (1 x 10(9) Pfu/ml Ad(5)-HGF, 1 ml); (c) medium-dose group (5 x 10(9) Pfu/ml Ad(5)-HGF, 1 ml); (d) high-dose group (1 x 10(10) Pfu/ml Ad(5)-HGF, 1 ml). Four weeks after left anterior descending coronary artery (LAD) ligation, different doses of Ad(5)-HGF were transferred in three therapeutic groups via right coronary artery. Four and seven weeks after LAD ligation, gate cardiac perfusion imaging was performed to evaluate cardiac perfusion and left ventricular ejection fraction (LVEF). Seven weeks after surgery, the apoptotic index of cardiocyte was observed by TUNEL, the expression of Bcl-2, Bax, alpha-SMA and Factor VIII in the border zones were evaluated by immunohistochemistry, respectively. Four weeks after myocardial infarction, no significant difference was observed among four groups. Three weeks after Ad(5)-HGF transfer, the improvement of cardiac perfusion and LVEF was obviously observed, especially after 1 x 10(10) Pfu Ad(5)-HGF transfer. TUNEL assay showed that 5 x 10(9) Pfu and 1 x 10(10) Pfu Ad(5)-HGF treatment had a obvious reduction in the apoptotic index compared with the null-Ad(5) group, especially after 1 x 10(10) Pfu Ad(5)-HGF treatment. The expression of Bcl-2 protein was increased and the expression of Bax protein was inhibited in the 5 x 10(9) Pfu and 1 x 10(10) Pfu Ad(5)-HGF groups compared with the null-Ad(5) group. The vessel density of Factor VIII(+) and alpha-SMA(+) was increased in Ad(5)-HGF groups compared with the null-Ad(5) group. There were no significant differences in angiogenesis, reducing apoptosis and ameliorating heart function between the 1 x 10(9) Pfu Ad(5)-HGF group and the null-Ad(5) group. Although no statistical difference was observed between 1 x 10(10) Pfu and 5 x 10(9) Pfu Ad(5)-HGF groups, the cardiac protective effects of 1 x 10(10) Pfu Ad(5)-HGF treatment were greater than 5 x 10(9) Pfu Ad(5)-HGF treatment. Different doses of Ad5-HGF injected via noninfarct-related artery could induce angiogenesis, reduce apoptosis and ameliorate heart function, and the cardiac protective effects of 1 x 10(10) Pfu Ad5-HGF is of most significance.