Measurements of All-Particle Energy Spectrum and Mean Logarithmic Mass of Cosmic Rays from 0.3 to 30 PeV with LHAASO-KM2A.

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15 PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.

Measurement of Ultra-High-Energy Diffuse Gamma-Ray Emission of the Galactic Plane from 10 TeV to 1 PeV with LHAASO-KM2A.

The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°10 TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60 TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.

[Microanatomy and functional MRI study of arcuate fasciculus and superior longitudinal fasciculus].

Objectives: To explore the microanatomy and functional MRI(fMRI) of arcuate fasciculus(AF) and superior longitudinal fasciculus(SLF),and to analyze their functions. Methods: Ten normal adult cadaveric head specimens (20 cerebral hemispheres) were fixed with 10% methanal at the Translational Research Institute for Neurological Disorders of the Wannan Medical Collegefrom February to December 2022.The Klingler fiber dissection technique was utilized to perform white matter fiber dissection,with a magnification ranging from 6 to 40.The study focused on the microanatomical structures of the AF and SLF,aiming to explore their relationships with deep brain fibers.Furthermore, six healthy adult volunteers who underwent fMRI of the brain were included.The collected diffusion tensor imaging (DTI) data were processed and integrated with the microanatomical findings for a comprehensive analysis. Results: After removing the gray matter of the cerebral cortex,the superficial U fibers were exposed.The long association fibers that beneath the U fibers were the AF and SLF,which were the main long association fibers in the superficial layers of the brain.The AF could be divided into dorsal and ventral parts,while the SLF could be divided into Ⅰ,Ⅱ,and Ⅲ.SLF Ⅰ lied within the upper bank of the cingulate sulcus,travels medial to the callosal sulcus.The SLF Ⅱ,Ⅲ,and the AF were located on the lateral surface of the brain.By removing the gray matter of the insular cortex and the extreme capsule,exposing the external capsule and claustrum.Subsequently,the AF and SLF Ⅱ,Ⅲ were dissected,revealing the corona radiata and sagittal stratum,along with other deep brain fibers.During the dissection,it was observed that there was a close connection between the AF,SLF Ⅱ,and the deep brain fibers.Furthermore,in the regions above the lateral fissure of the cerebral hemisphere,there was no direct connection of long association fibers between the gray matter cortex and the deep U fibers in the coronal plane.These findings were further supported by DTI studies. Conclusions: The AF and SLF are the major long association fibers that located in the superficial layers of the brain,and closely connect to the gray matter cortex and U fibers,even closely relate with deep brain fibers.In the regions above the lateral fissure of the hemisphere,only the AF and SLF Ⅱ and Ⅲ serve as superficial long association fibers in the anterior-posterior direction.These fibers are likely involved in the transmission of brain functional information between the top and bottom gray matter cortex in the coronal plane above the lateral fissure.

A tera-electron volt afterglow from a narrow jet in an extremely bright gamma-ray burst.

Some gamma-ray bursts (GRBs) have a tera-electron volt (TeV) afterglow, but the early onset of this has not been observed. We report observations with the Large High Altitude Air Shower Observatory (LHAASO) of the bright GRB 221009A, which serendipitously occurred within the instrument's field of view. More than 64,000 photons >0.2 TeV were detected within the first 3000 seconds. The TeV flux began several minutes after the GRB trigger and then rose to a peak ~10 seconds later. This was followed by a decay phase, which became more rapid ~650 seconds after the peak. We interpret the emission using a model of a relativistic jet with half-opening angle of ~0.8°. This is consistent with the core of a structured jet and could explain the high isotropic energy of this GRB.

Exploring Lorentz Invariance Violation from Ultrahigh-Energy γ Rays Observed by LHAASO.

Recently, the LHAASO Collaboration published the detection of 12 ultrahigh-energy γ-ray sources above 100 TeV, with the highest energy photon reaching 1.4 PeV. The first detection of PeV γ rays from astrophysical sources may provide a very sensitive probe of the effect of the Lorentz invariance violation (LIV), which results in decay of high-energy γ rays in the superluminal scenario and hence a sharp cutoff of the energy spectrum. Two highest energy sources are studied in this work. No signature of the existence of the LIV is found in their energy spectra, and the lower limits on the LIV energy scale are derived. Our results show that the first-order LIV energy scale should be higher than about 10^{5} times the Planck scale M_{Pl} and that the second-order LIV scale is >10^{-3}M_{Pl}. Both limits improve by at least one order of magnitude the previous results.

Constraints on Heavy Decaying Dark Matter from 570 Days of LHAASO Observations.

The kilometer square array (KM2A) of the large high altitude air shower observatory (LHAASO) aims at surveying the northern γ-ray sky at energies above 10 TeV with unprecedented sensitivity. γ-ray observations have long been one of the most powerful tools for dark matter searches, as, e.g., high-energy γ rays could be produced by the decays of heavy dark matter particles. In this Letter, we present the first dark matter analysis with LHAASO-KM2A, using the first 340 days of data from 1/2-KM2A and 230 days of data from 3/4-KM2A. Several regions of interest are used to search for a signal and account for the residual cosmic-ray background after γ/hadron separation. We find no excess of dark matter signals, and thus place some of the strongest γ-ray constraints on the lifetime of heavy dark matter particles with mass between 10^{5} and 10^{9} GeV. Our results with LHAASO are robust, and have important implications for dark matter interpretations of the diffuse astrophysical high-energy neutrino emission.

Peta-electron volt gamma-ray emission from the Crab Nebula.

The Crab Nebula is a bright source of gamma rays powered by the Crab Pulsar's rotational energy through the formation and termination of a relativistic electron-positron wind. We report the detection of gamma rays from this source with energies from 5 × 10-4 to 1.1 peta-electron volts with a spectrum showing gradual steepening over three energy decades. The ultrahigh-energy photons imply the presence of a peta-electron volt electron accelerator (a pevatron) in the nebula, with an acceleration rate exceeding 15% of the theoretical limit. We constrain the pevatron's size between 0.025 and 0.1 parsecs and the magnetic field to ≈110 microgauss. The production rate of peta-electron volt electrons, 2.5 × 1036 ergs per second, constitutes 0.5% of the pulsar spin-down luminosity, although we cannot exclude a contribution of peta-electron volt protons to the production of the highest-energy gamma rays.

Measurement of the Cosmic Ray Helium Energy Spectrum from 70 GeV to 80 TeV with the DAMPE Space Mission.

The measurement of the energy spectrum of cosmic ray helium nuclei from 70 GeV to 80 TeV using 4.5 years of data recorded by the Dark Matter Particle Explorer (DAMPE) is reported in this work. A hardening of the spectrum is observed at an energy of about 1.3 TeV, similar to previous observations. In addition, a spectral softening at about 34 TeV is revealed for the first time with large statistics and well controlled systematic uncertainties, with an overall significance of 4.3σ. The DAMPE spectral measurements of both cosmic protons and helium nuclei suggest a particle charge dependent softening energy, although with current uncertainties a dependence on the number of nucleons cannot be ruled out.

Rapid Qualitative and Quantitative Analysis of Caffeine and Sodium Benzoate in Annaca by Infrared Spectroscopy.

ABSTRACT: Objective To establish an infrared spectroscopic method for the rapid qualitative and quantitative analysis of caffeine and sodium benzoate in Annaka samples. Methods Qualitative and quantitative modeling samples were prepared by mixing high-purity caffeine and sodium benzoate. The characteristic absorption peaks of caffeine and sodium benzoate in Annaka samples were determined by analyzing the infrared spectra of the mixed samples. The quantitative model of infrared spectra was established by partial least squares （PLS）. Results By analyzing the infrared spectra of 17 mixed samples of caffeine and sodium benzoate （the purity of caffeine ranges from 10% to 80%）, the characteristic absorption peaks for caffeine were determined to be 1 698, 1 650, 1 237, 972, 743, and 609 cm-1. The characteristic absorption peaks for sodium benzoate were 1 596, 1 548, 1 406, 845, 708 and 679 cm-1. When the detection of all characteristic absorption peaks was the positive identification criteria, the positive detection rate of caffeine and sodium benzoate in 48 seized Annaka samples was 100%. The linear range of PLS quantitative model for caffeine was 10%-80%, the coefficient of determination （ R2） was 99.9%, the root mean square error of cross validation （RMSECV） was 0.68%, and the root mean square error of prediction （RMSEP） was 0.91%; the linear range of PLS quantitative model for sodium benzoate was 20%-90%, the R2 was 99.9%, the RMSECV was 0.91% and the RMSEP was 1.11%. The results of paired sample t test showed that the differences between the results of high performance liquid chromatography method and infrared spectroscopy method had no statistical significance. The established infrared quantitative method was used to analyze 48 seized Annaka samples, the purity of caffeine was 27.6%-63.1%, and that of sodium benzoate was 36.9%-72.3%. Conclusion The rapid qualitative and quantitative analysis of caffeine and sodium benzoate in Annaka samples by infrared spectroscopy method could improve identification efficiency and reduce determination cost.

Sex-Based Diverse Plaque Microbiota in Children with Severe Caries.

Severe early childhood caries (S-ECC) is a multifactorial disease that can lead to suffering and reduced oral health-related quality of life in young children. The bacterial and fungal composition of dental plaque and how children's sex is associated with S-ECC are largely unknown. In this study, V4-16S rRNA and ITS1 rRNA gene amplicon sequencing was used to compare the plaque bacteriome and mycobiome of children <72 mo of age: 40 with S-ECC (15 males, 25 females) and 40 caries-free (19 males, 21 females). Health- and nutrition-related questionnaire data were also investigated. This study aimed to analyze potential sex-based differences in the supragingival plaque microbiota of young children with S-ECC and those caries-free. Behavioral and nutritional habit differences were observed between children with S-ECC and those caries-free and between male and female children. Overall, higher levels of Veillonella dispar, Streptococcus mutans, and other bacterial species were found in the S-ECC group as compared with caries-free controls (P < 0.05). A significant difference in the abundance of Neisseria was observed between males and females with S-ECC (P < .05). Fungal taxonomic analysis showed significantly higher levels of Candida dubliniensis in the plaque of children with S-ECC as compared with those caries-free (P < 0.05), but no differences were observed with Candida albicans (P > 0.05). Significant differences in the relative abundance of Mycosphaerella, Cyberlindnera, and Trichosporon fungal species were also observed between the caries-free and S-ECC groups (P < 0.05). Machine learning analysis revealed the most important bacterial and fungal species for classifying S-ECC versus caries-free. Different patterns of crosstalk between microbial species were observed between male and female children. Our work demonstrates that plaque microbiota and sex may be important determinants for S-ECC and could be factors to consider for inclusion in caries risk assessment tools.

Measurement of the cosmic ray proton spectrum from 40 GeV to 100 TeV with the DAMPE satellite.

The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2 1/2 years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.

MicroRNA-409 promotes recovery of spinal cord injury by regulating ZNF366.

OBJECTIVE: To explore the role of microRNA-409 in spinal cord injury (SCI) recovery and its underlying mechanism. MATERIALS AND METHODS: The mouse SCI model was first established, and the difference in recovery of grip strength was detected. MicroRNA-409 expressions in mice tissues from sham operation group and SCI group were detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). We further increased microRNA-409 level in mice spinal cord by plasmids transfection. Luciferase activity was detected to verify the direct binding of microRNA-409 and ZNF366. RESULTS: The grip strength in both groups was temporarily decreased after surgery, while the grip strength in SCI group was always remarkably lower than that of the sham operation group since the first week after the surgery, suggesting the successful construction of mouse SCI model. MicroRNA-409 expression in the SCI group was gradually decreased from the postoperative 3rd day, which was remarkably lower than that of the sham group. Additionally, ZNF366 expression in the SCI group began to increase from the first day after the surgery, which was markedly higher than that of the sham group. After injection of exogenous microRNA-409, ZNF366 expression in the SCI group showed a remarkable decrease compared to that of the sham operation group. We also confirmed that ZNF366 was the target gene of microRNA-409 by bioinformatics analysis and luciferase activity assay. CONCLUSIONS: MicroRNA-409 is downregulated after spinal cord injury. Overexpression of microRNA-409 directly targets ZNF366 and promotes the recovery of spinal cord injury.

Study on the role of Hsa-miR-382-5p in epidural fibrosis.

OBJECTIVE: To investigate the role and potential mechanism of human serum albumin (hsa)-micro ribonucleic acid (miR)-382-5p in epidural fibrosis formation after laminectomy. MATERIALS AND METHODS: Cells were transfected with miR-382-5p mimic or miR-382-5p inhibitor. Then, 3-(4,5)-dimethylthiahiazol (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay was employed to detect the effect of miR-382-5p on proliferation, and Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to examine the expressions of miR-382-5p and fibrosis-related proteins after treatment with transforming growth factor beta (TGF-ß). Luciferase assay and immunofluorescent staining were done to confirm whether collagen I A1 is a target of miR-382-5p. RESULTS: MTT assay demonstrated that miR-382-5p had no significant effect on fibroblast proliferation. Expressions of miR-382-5p and fibrosis-related proteins were remarkably increased after TGF-ß treatment. Collagen I A1 was acknowledged as a target of miR-382-5p. MiR-382-5p mimic statistically enhanced the level of collagen I A1, and miR-382-5p enhanced the expressions of collagen I A1. CONCLUSIONS: Increased miR-382-5p promotes epidural fibrosis by increasing collagen I A1 expression, and miR-382-5p may be a potential novel molecular target for the treatment of epidural fibrosis.

Establishment and evaluation of an indirect immunofluorescence assay for the detection of salmonid alphavirus.

Salmonid alphaviruses (SAV) severely infect farmed salmonids and rainbow trout. Owing to the recent increase in fish import trade, several SAV unreported countries, such as China, may face serious threat of this infection. Thus, it is necessary to develop efficient detection methods for the prevention and diagnosis of SAV infection. In this study, we selected a conserved segment of the SAV E1 protein as a target immunogen for the preparation of monoclonal antibodies (mAbs) specific to SAV. A sensitive indirect immunofluorescence (IF) method was developed using 26E9C2 mAb that detected E1 protein and identified subtypes 1, 2 and 5 of SAV. Thus, this assay provides a sensitive and specific detection method, and an improved technical support for the clinical diagnosis and epidemiological study of SAV. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we successfully prepared two monoclonal antibodies (mAbs) against three subtypes of salmonid alphavirus (SAV), and established an indirect immunofluorescence assay that can be used to diagnose and prevent SAV from entering SAV unreported countries, such as China, through international trade. The application of this method will contribute to controlling SAV infection and reducing economic losses.

Protective effects of morphine preconditioning in delayed phase on myocardial ischemia-reperfusion injury in rabbits.

The aim of this study was to investigate the protective mechanisms of delayed-phase morphine preconditioning on myocardial ischemia-reperfusion injury. Thirty healthy male New Zealand white rabbits were randomly divided into three groups: a sham operation group (C), ischemia-reperfusion group (I/R), and delayed-phase morphine preconditioning group (M) (N = 10/group). Rabbits in the C group received thoracotomy for 160 min. Rabbits in the I/R group received left artery blockage for 40 min and reperfusion for 120 min. Rabbits in the M group received 1.0 mg/kg intravenous morphine 24 h prior to the identical treatment as the rabbits in the I/R group. In each group, the interleukin (IL)-10 and tumor necrosis factor (TNF)-α levels were detected at five time points: 20 min before the left coronary artery blockage (T1), 20 and 40 min after the left coronary artery blockage (T2 and T3, respectively), and 1 and 2 h after the myocardial reperfusion (T4 and T5, respectively). After reperfusion, the infarction size was measured with Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining. Compared with the C group, serum IL-10 and TNF-α concentrations increased in the I/R and M groups; the difference was significant (P < 0.05). When compared with the I/R group, the IL-10 concentrations in the M group were significantly increased (P < 0.05), but the infarction size and TNF-α concentrations were significantly decreased (P < 0.05). These results suggested that delayed-phase morphine preconditioning might achieve myocardial protection through the regulation and balance of inflammatory cytokines.

Effect of morphine preconditioning in the delayed phase on the expression of p38 mitogen-activated protein kinase in a rabbit model of myocardial ischemia-reperfusion injury.

This study aimed to investigate the protective effects of delayed morphine preconditioning on myocardial ischemia-reperfusion injury. We randomly divided 30 rabbits into three groups with 10 rab-bits in each group as follows: sham operation group (C group), isch-emia-reperfusion group (I/R group), and morphine pretreatment group (M group). Rabbits in C Group received left coronary without blocking for 160 min. The left descending artery of rabbits in the I/R group was blocked for 40 min and reperfused for 120 min. Rabbits in the M group received intravenous administration of 1.0 mg/kg morphine; after 24 h, rabbits in this group received the same treatment as that administered to the I/R group. We determined tumor necrosis factor alpha (TNF-α) levels in blood samples from the internal carotid artery of rabbits in each group 20 min before occlusion of the left descending coronary artery, 20 and 40 min after occlusion of the left descending coronary artery, and 1 and 2 h after myocardial reperfusion. After 120 min of reperfusion, immunoblotting was used to measure the activity levels of myocardial p38 mitogen-activated protein kinase (MAPK); in addition, the infarct size was measured. Compared to the I/R group, the M group showed a significant decrease in TNF-α levels, p38 MAPK activity, and the myocardial infarct size (I/R group 37.8% ± 1.7% vs 21.5% ± 2.4%; P < 0.05). Thus, morphine preconditioning in the delayed phase may exert protective effects on myocardial I/R injury by inhibiting myocar-dial p38 MAPK activity and decreasing TNF-α production.

Effects of isoflurane preconditioning in the delayed phase on myocardial tumor necrosis factor alpha levels and caspase-3 protein expression in a rabbit model of ischemia-reperfusion injury.

This study aimed to investigate the protective effects and the mechanisms underlying these effects of isoflurane preconditioning in the delayed phase of myocardial ischemia-reperfusion injury. We randomly divided 30 healthy male New Zealand white rabbits into three groups with 10 rabbits in each group as follows: sham operation group (C group), ischemia-reperfusion group (I/R group), and 2.0% isoflurane preconditioning group (S group). Rabbits in the C group received thoracotomy for 160 min. Rabbits in the I/R group underwent left coronary artery occlusion for 40 min and reperfusion for 120 min. Rabbits in the S group received inhalation of 2.0% isoflurane and 100% oxygen for 2 h; after 24 h, rabbits in this group received the same treatment as that administered to rabbits in the I/R group. We examined the tumor necrosis factor alpha (TNF-α) levels in each group 20 min before occlusion of the left coronary, 20 and 40 min after occlusion of the left coronary artery, and 1 and 2 h after myocardial reperfusion. After reperfusion, immunoblotting was used to measure the myocardial caspase-3 expression levels, and the infarct size was measured using Evans blue and tetrazolium chloride staining. The levels of TNF-α and caspase-3 were lower in the S group than in the I/R group, and the myocardial infarct size decreased in the S group. Thus, isoflurane preconditioning in the delayed phase exerted protective effects by decreasing the myocardial caspase-3 expression and TNF-α production in a rabbit model of ischemia-reperfusion injury.

Ginkgo biloba extract postconditioning reduces myocardial ischemia reperfusion injury.

We examined the protective effects of Ginkgo biloba extract (EGb761) postconditioning on myocardial ischemia reperfusion injury in rabbits. Four groups of 8 white rabbits were allocated to: pseudo surgery group: the left coronary was lined without blocking for 160 min after thoracotomy; ischemia and reperfusion group (IR): the left anterior descending coronary artery was blocked for 40 min and reperfused for 120 min; ischemic postconditioning group: the left anterior descending artery was ligated for 40 min, reopened for 30 s and ligated for 30 s, repeated three times, and then reperfused for 120 min; EGb761 postconditioning group (E): 100 mg/kg EGb761 was injected into a vein while the left coronary artery was opened for 1 min. The reperfusion took 120 min. Internal carotid arterial blood in each group was collected for cTnI measurement at five times: 20 min before occlusion of the left coronary artery, 20 min after left coronary artery occlusion, 40 min after left coronary artery occlusion, 1 h after myocardial reperfusion, and 2 h after myocardial reperfusion. Superoxide dismutase (SOD), malondialdehyde (MDA) in the centrifuged blood and myocardial infarction area were measured at the end of reperfusion. We found that the serum cTnI concentrations in the E group during reperfusion decreased significantly compared with those in the IR group. The infarction area was significantly lower in the E group than that in the IR group. The SOD activity in the E group was increased compared with that in the IR group; the MDA content decreased significantly in the E group compared with that in the IR group. We conclude that G. biloba extract postconditioning had myocardial protection effects by reducing the generation of oxygen-free radicals and increasing the antioxidant capacity of the myocardial cells.

Epigenetic DNA methylation in the promoters of peroxisome proliferator-activated receptor γ in chicken lines divergently selected for fatness.

Peroxisome proliferator-activated receptor γ is a master regulator of adipocyte differentiation and function. Expression of PPARγ in mammals is regulated by DNA methylation; however, it is currently unknown whether chicken PPARγ expression is regulated by DNA methylation. To enhance our understanding of molecular mechanisms underlying chicken adipose tissue development and adipogenesis, we investigated the promoter methylation status and gene expression of PPARγ gene in Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF). Deoxyribonucleic acid methylation was analyzed by bisulfite sequencing method, and mRNA expression was detected by real-time quantitative real time reverse-transcription polymerase chain reaction (RT-PCR). The analyzed region located from -1,175 to -301 bp upstream of the translation start codon ATG contains 6 CpG dinucleotides, which are located at positions -1,014, -796, -625, -548, -435, and -383 bp, respectively. The results revealed that the 3 CpGs at positions -548, -435, and -383 bp showed differential methylation between the lean and fat chicken lines, but the other 3 CpG sites at positions -1,014, -796, and -625 bp did not. PPARγ gene promoter methylation in both chicken lines decreased with age, and PPARγ promoter methylation levels were significantly higher in lean than fat broilers at 2 wk of age (79.9 to 64.5%; P < 0.0001), at 3 wk of age (66.7 to 58.3%; P < 0.0001), and at 7 wk of age (50.0 to 42.7%; P = 0.0004). Real-time quantitative RT-PCR analysis showed that, negatively correlated with DNA methylation (Pearson's r = -0.653, P = 0.0057), PPARγ expression was increased with age and significantly lower in lean than fat chicken lines at 2, 3, and 7 wk of age (P < 0.0001). In conclusion, our findings suggest that chicken PPARγ is regulated by DNA methylation during adipose tissue development.

Effect of quercetin on P-glycoprotein transport ability in Chinese healthy subjects.

OBJECTIVES: The aim of this study was to investigate the effect of quercetin on P-glycoprotein (P-gp) transport ability in vivo. SUBJECTS/METHODS: Genotype data were available from a total of 165 health volunteers. An open, randomized, two-period crossover clinical trial was performed in eighteen subjects with different MDR1 3435 C/T genotypes. All subjects took 500 mg quercetin or placebo daily from 1st to 13th day or from 43 st to 55th day, and 100 mg talinolol was given at the 14th or 56th day. The washout period is 28 days. RESULTS: In this study, we found the values of area under the curve (AUC)0-48 h, AUC0-∞ and Cmax of talinolol in all subjects significantly decreased (6496.6 ± 2389.9 vs 7809.5 ± 2386.8 ng.h/ml, P=0.04), (8414.7 ± 344.8 vs 10478.2 ± 4195.4 ng.h/ml, P=0.03), (412.9 ± 132.6 vs 543.3 ± 97.9 ng.h/ml, P=0.01) after administration of quercetin, respectively. There were no significant differences in tmax and t1/2 of talinolol. The results also showed AUC0-48 h (5598.6 ± 2202.1 vs 8229.4 ± 1491.7 ng.h/ml, P=0.02) and AUC0-∞ (7110.0 ± 3437.0 vs 12681.2 ± 4828.2 ng.h/ml, P=0.01) of talinolol to be significantly decreased in MDR1 3435 TT individuals administered of quercetin. The Cmax of talinolol in MDR1 3435 TT (382.4 ± 149.1 vs 584.9 ± 115.2 ng/ml, P=0.04) and MDR1 3435 CT (383.5 ± 104.9 vs 554.6 ± 80.6 ng/ml, P=0.01) individuals significantly decreased after the administration of quercetin. CONCLUSIONS: Quercetin significantly induced the activity of P-gp and this induced effect was more obvious in MDR1 3435 TT individuals.