Berberine (BBR) has been confirmed to have multiple bioactivities in clinic, such as cholesterol-lowering, anti-diabetes, cardiovascular protection and anti- inflammation. However, BBR's plasma level ...is very low; it cannot explain its pharmacological effects in patients. We consider that the in vivo distribution of BBR as well as of its bioactive metabolites might provide part of the explanation for this question. In this study, liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MS(n)-IT-TOF) as well as liquid chromatography that coupled with tandem mass spectrometry (LC-MS/MS) was used for the study of tissue distribution and pharmacokinetics of BBR in rats after oral administration (200 mg/kg). The results indicated that BBR was quickly distributed in the liver, kidneys, muscle, lungs, brain, heart, pancreas and fat in a descending order of its amount. The pharmacokinetic profile indicated that BBR's level in most of studied tissues was higher (or much higher) than that in plasma 4 h after administration. BBR remained relatively stable in the tissues like liver, heart, brain, muscle, pancreas etc. Organ distribution of BBR's metabolites was also investigated paralleled with that of BBR. Thalifendine (M1), berberrubine (M2) and jatrorrhizine (M4), which the metabolites with moderate bioactivity, were easily detected in organs like the liver and kidney. For instance, M1, M2 and M4 were the major metabolites in the liver, among which the percentage of M2 was up to 65.1%; the level of AUC (0-t) (area under the concentration-time curve) for BBR or the metabolites in the liver was 10-fold or 30-fold higher than that in plasma, respectively. In summary, the organ concentration of BBR (as well as its bioactive metabolites) was higher than its concentration in the blood after oral administration. It might explain BBR's pharmacological effects on human diseases in clinic.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Berberine (BBR) has been confirmed to show extensive bioactivities for the treatments of diabetes and hypercholesterolemia in clinic. However, there are few pharmacokinetic studies to elucidate the ...excretions of BBR and its metabolites. Our research studied the excretions of BBR and its metabolites in rats after oral administration (200 mg/kg). Metabolites in bile, urine, and feces were detected by liquid chromatography coupled to ion trap time‐of‐flight mass spectrometry; meanwhile, a validated liquid chromatography coupled with tandem mass spectrometry method was developed for their quantifications. Sixteen metabolites, including 10 Phase I and six Phase II metabolites were identified and clarified after dosing in vivo. Total recovered rate of BBR was 22.83% (19.07% of prototype and 3.76% of its metabolites) with 9.2 × 10−6% in bile (24 h), 0.0939% in urine (48 h), and 22.74% in feces (48 h), respectively. 83% of BBR was excreted as thalifendine (M1) from bile, whereas thalifendine (M1) and berberrubine (M2) were the major metabolites occupying 78% of urine excretion. Most of BBR and its metabolites were found in feces containing 84% of prototype. In summary, we provided excretion profiles of BBR and its metabolites after oral administration in rats in vivo.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
This paper describes perturbation analysis of nonlinear signal generation in apodized film bulk acoustic resonators using a multi-branch
LCR
equivalent circuit where all necessary simulation ...parameters are derived by the two-dimensional (2D) scalar wave model. Nonlinear signals are evaluated by adding two voltage sources representing nonlinear strain and electric flux, and their amplitude is determined by currents in the circuit for linear analysis. Simulated second and third harmonic responses agree well with experimental ones. The magnification mechanism of spurious resonances is also discussed.
Abstract
This paper proposes the use of a two-dimensional scalar wave model for fast analysis of apodized AlN-based radio frequency bulk acoustic wave devices. First, the working principle and model ...setup is introduced. Only one particular Lamb mode (S
1−
) is considered, and its behavior is modeled by a simple scalar wave equation looking from the top surface. Multiple layers are added to the side boundaries so that mode conversion to other modes is treated as leakage to surroundings. The wavenumber of field distribution for each resonance mode is calculated, and then its excitation coefficient, quality factor, and resonance frequency are derived. The device input admittance is calculated by applying derived parameters to the equivalent circuit. A series of oval-shaped AlN-based film bulk acoustic resonator devices are simulated and compared with experimental results. The theoretical results agreed well with the experimental ones, and accuracy and effectiveness of the present analysis are verified.
Abstract
This paper describes the design and fabrication of spurious-free thickness-shear bulk acoustic resonators (TSBARs) using the lithium niobate (LN) plate. Previously, the authors conjected ...from the experiment on the TSBAR that cut-off edges with crystal LN
x
plane serve as ideal reflectors for the piston mode operation, and complete suppression is possible by adding the standard piston mode design to the other edges normal to the
X
-axis. Following this conjecture, the traditional piston mode structure is designed by the traditional two-dimensional finite element method, and the TSBAR is fabricated following the design. The experiment showed complete suppression of the transverse mode resonances, and the conjecture was verified.
Aims
Failure of neural tube closure resulting from excessive apoptosis leads to neural tube defects (NTDs). NADPH oxidase 4 (NOX4) is a critical mediator of cell growth and death, yet its role in ...NTDs has never been characterized. NOX4 is a potential target of miR‐322, and we have previously demonstrated that miR‐322 was involved in high glucose‐induced NTDs. In this study, we investigated the effect of NOX4 on the embryonic neuroepithelium in NTDs and reveal a new regulatory mechanism for miR‐322 that disrupts neurulation by ameliorating cell apoptosis.
Methods
All‐trans‐retinoic acid (ATRA)‐induced mouse model was utilized to study NTDs. RNA pull‐down and dual‐luciferase reporter assays were used to confirm the interaction between NOX4 and miR‐322. In mouse neural stem cells and whole‐embryo culture, Western blot and TUNEL were carried out to investigate the effects of miR‐322 and NOX4 on neuroepithelium apoptosis in NTD formation.
Results
NOX4, as a novel target of miR‐322, was upregulated in ATRA‐induced mouse model of NTDs. In mouse neural stem cells, the expression of NOX4 was inhibited by miR‐322; still further, NOX4‐triggered apoptosis was also suppressed by miR‐322. Moreover, in whole‐embryo culture, injection of the miR‐322 mimic into the amniotic cavity attenuated cell apoptosis in NTD formation by silencing NOX4.
Conclusion
miR‐322/NOX4 plays a crucial role in apoptosis‐induced NTD formation, which may provide a new understanding of the mechanism of embryonic NTDs and a basis for potential therapeutic target against NTDs.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
The Cambrian Series 2–Miaolingian transition is a pivotal period during Earth history, which witnessed the decline of biodiversity and the reduction in biomass, i.e., the redlichiid–olenellid ...trilobite extinction. The notable δ13C excursion (RECE) near the Cambrian Series 2–Miaolingian boundary in east Gondwana and China apparently corresponds with the redlichiid trilobite extinction. To better understand the causal mechanism of this biotic crisis, we report the carbon isotope stratigraphy and facies changes from Cambrian Series 2–Miaolingian transition of the Mantou Formation on the southern North China Craton. The carbon isotope excursions at the Cambrian Series 2–Miaolingian transition in the study area are 0.7‰ in the Chishanhe section and −0.2‰ in the Luoquan section, respectively, showing a weak negative excursion or even no negative excursion. The sedimentary environments in the study area gradually changed through time from a clastic tidal flat to a carbonate platform across the transition, which indicated a gradual rise in sea level, with anoxic conditions occurring predominantly before the RECE δ13C excursion. Microbially induced sedimentary structures and oncoids occurred widely at the top of Cambrian Series 2. Abundant metazoan trace fossils were preserved in the Miaolingian Series of the study area. The evolution of biogenic structures across the Cambrian Series 2–Miaolingian transition indicates the emergence of harsh environments associated with the proliferation of MISS and oncoids at the RECE horizon and the recovery of benthic metazoan fauna after the RECE biotic crisis.
Full text
Available for:
CEKLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Pneumonia caused by the 2019 novel Coronavirus (COVID‐2019) shares overlapping signs and symptoms, laboratory findings, imaging features with influenza A pneumonia. We aimed to identify ...their clinical characteristics to help early diagnosis.
Methods
We retrospectively retrieved data for laboratory‐confirmed patients admitted with COVID‐19–induced or influenza A–induced pneumonia from electronic medical records in Ningbo First Hospital, China. We recorded patients' epidemiological and clinical features, as well as radiologic and laboratory findings.
Results
The median age of influenza A cohort was higher and it exhibited higher temperature and higher proportion of pleural effusion. COVID‐19 cohort exhibited higher proportions of fatigue, diarrhea and ground‐glass opacity and higher levels of lymphocyte percentage, absolute lymphocyte count, red‐cell count, hemoglobin and albumin and presented lower levels of monocytes, c‐reactive protein, aspartate aminotransferase, alkaline phosphatase, serum creatinine. Multivariate logistic regression analyses showed that fatigue, ground‐glass opacity, and higher level of albumin were independent risk factors for COVID‐19 pneumonia, while older age, higher temperature, and higher level of monocyte count were independent risk factors for influenza A pneumonia.
Conclusions
In terms of COVID‐19 pneumonia and influenza A pneumonia, fatigue, ground‐glass opacity, and higher level of albumin tend to be helpful for diagnosis of COVID‐19 pneumonia, while older age, higher temperature, and higher level of monocyte count tend to be helpful for the diagnosis of influenza A pneumonia.
Fatigue, ground‐glass opacity and higher level of albumin tend to be helpful for diagnosis of COVID‐19 pneumonia, while older age, higher temperature, and higher level of monocytes count tend to be helpful for the diagnosis of influenza A pneumonia.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The large yellow croaker (Larimichthys crocea) is among the most important commercial aquaculture fish species in China. Although croakers are known to produce sounds, especially during the spawning ...season, the relationship between vocal behavior and spawning activity in this species remains largely unknown. In this study, sound production of cultured sexually mature L. crocea was monitored before and during the spawning periods. We estimated the spawning time of L. crocea by examining the embryonic development of fertilized eggs, and divided reproductive stages into four periods (T1-T4) based on the timing of hormonal treatment and spawning of L. crocea. A total of 1340 calls from four periods were analyzed to investigate the relationship between the call characteristics and the different spawning periods. The results demonstrated that L. crocea produced low-frequency pulsed sounds, and sound features differed significantly across reproductive stages in all four periods. During the spawning periods (T3 and T4), longer sounds were produced, with a higher number of pulses per call, a shorter pulse period, and a higher peak frequency than those produced before the spawning periods (T1 and T2). ‘Chorus’ calling was closely related to spawning activity. During the ‘chorus’ periods, the sound pressure level of soundscape in the tank increased by ~30 dB compared to prior no ‘chorus’ periods. Therefore, L. crocea vocalizations can be used as important indicators to determine spawning states and spawning time. We demonstrate that passive acoustic monitoring of L. crocea can provide information about the species spawning time, which will aid in improving both aquaculture management and discovery and protection of spawning habitats of wild L. crocea populations.
•Larimichthys crocea is a typical soniferous fish species.•The spawning time is estimated by microscopic observations of the eggs.•L. crocea calls' characteristics vary across different reproductive states.•L. crocea vocalizations can inform about reproductive states.•Acoustic monitoring of L. crocea calls can promote aquaculture management.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PDF
