Impact of Microbubble Degradation and Flow Velocity on Subharmonic-aided Pressure Estimation (SHAPE): An Experimental Investigation.

OBJECTIVE: This study aimed to investigate the impact of microbubble degradation and flow velocity on Sub-Harmonic Aided Pressure Estimation (SHAPE), and to explore the correlation between subharmonic amplitude and pressure as a single factor. METHODS: We develop an open-loop vascular phantom platform system and utilize a commercial ultrasound machine and microbubbles for subharmonic imaging. Subharmonic amplitude was measured continuously at constant pressure and flow velocity to assess the impact of microbubble degradation. Flow velocity was varied within a range of 4-14 cm/s at constant pressure to investigate its relationship to subharmonic amplitude. Furthermore, pressure was varied within a range of 10-110 mm Hg at constant flow velocity to assess its isolated effect on subharmonic amplitude. RESULTS: Under constant pressure and flow velocity, subharmonic amplitude exhibited a continuous decrease at an average rate of 0.221 dB/min, signifying ongoing microbubble degradation during the experimental procedures. Subharmonic amplitude demonstrated a positive correlation with flow velocity, with a variation ratio of 0.423 dB/(cm/s). Under controlled conditions of microbubble degradation and flow velocity, a strong negative linear correlation was observed between pressure and subharmonic amplitude across different Mechanical Index (MI) settings (all R2 > 0.90). The sensitivity of SHAPE was determined to be 0.025 dB/mmHg at an MI of 0.04. CONCLUSION: The assessment of SHAPE sensitivity is affected by microbubble degradation and flow velocity. Excluding the aforementioned influencing factors, a strong linear negative correlation between pressure and subharmonic amplitude was still evident, albeit with a sensitivity coefficient lower than previously reported values.

Nucleophile-Controlled Trapping of Gold Carbene by Nitriles and Water: Synthesis of 5H-Pyrimido[5,4-b]indoles and 2-Benzylidene-3-indolinones.

A gold-catalyzed, nucleophile-controlled cascade reaction of N-(2-azidophenyl-ynyl)methanesulfonamides with nitriles and water is described that provides structurally diverse 5H-pyrimido[5,4-b]indoles and 2-benzylidene-3-indolinones in good to excellent yields. Mechanistic studies indicate that the ß-sulfonamido-α-imino gold carbene is the key intermediate which is generated through the gold-catalyzed cyclization of N-(2-azidophenyl-ynyl)methanesulfonamides and undergoes formal [4 + 2] cascade annulation with nitriles and intramolecular SN2' type reaction with water, respectively.

Quantification of the renal sinus fat and exploration of its relationship with ectopic fat deposition in normal subjects using MRI fat fraction mapping.

Purpose: To determine the renal sinus fat (RSF) volume and fat fraction (FF) in normal Chinese subjects using MRI fat fraction mapping and to explore their associations with age, gender, body mass index (BMI) and ectopic fat deposition. Methods: A total of 126 subjects were included in the analysis. RSF volume and FF, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) area, and hepatic and pancreatic FFs were measured for each subject. The comparisons in gender were determined using two-tailed t-tests or the nonparametric Mann-Whitney U-test for normally or non-normally distributed data for continuous variables and the chi-square test for categorical variables. Comparisons of RFS volume and FF between right and left kidneys were determined using paired sample t-tests. Multivariable logistic models were performed to confirm whether RSF differences between men and women are independent of VAT or SAT area. When parameters were normally distributed, the Pearson correlation coefficient was used; otherwise, the Spearman correlation coefficient was applied. Results: The RSF volumes (cm3) of both kidneys in men (26.86 ± 8.81 for right and 31.62 ± 10.32 for left kidneys) were significantly bigger than those of women (21.47 ± 6.90 for right and 26.03 ± 8.55 for left kidneys) (P < 0.05). The RSF FFs (%) of both kidneys in men (28.33 ± 6.73 for right and 31.21 ± 6.29 for left kidneys) were significantly higher than those of the women (23.82 ± 7.74 for right and 27.92 ± 8.15 for left kidneys) (P < 0.05). The RSF differences between men and women are independent of SAT area and dependent of VAT area (except for right RSF volume). In addition, the RSF volumes and FFs in both kidneys in the overall subjects show significant correlations with age, BMI, VAT area, hepatic fat fraction and pancreatic fat fraction (P < 0.05). However, the patterns of these correlations varied by gender. The RSF volume and FF of left kidney were significantly larger than those of the right kidney (P < 0.05). Conclusion: The association between renal sinus fat and ectopic fat deposition explored in this study may help establish a consensus on the normal values of RSF volume and FF for the Chinese population. This will facilitate the identification of clinicopathological changes and aid in the investigation of whether RSF volume and FF can serve as early biomarkers for metabolic diseases and renal dysfunction in future studies.

Vascular toxicity of multi-walled carbon nanotubes targeting vascular endothelial growth factor.

Multiwalled carbon nanotubes (MWCNTs) are currently widely used and are expected to be used as drug carriers and contrast agents in clinical practice. Previous studies mainly focused on their lung toxicity; therefore, their effects on the vascular endothelium are unclear. In this study, a human angiogenesis array was used to determine the effect of MWCNTs on the expression profile of angiogenic factors in endothelial cells and to clarify the role of vascular endothelial growth factor (VEGF) in MWCNT-induced endothelial cell injury at the cellular and animal levels. The results indicated that MWCNTs (20-30 nm and 30-50 nm) could enter endothelial cells and disrupt human umbilical vein endothelial cell (HUVECs) activity in a concentration-dependent manner. MWCNTs disrupted the tube formation ability and cell migration function of HUVECs. The results from a Matrigel Plug experiment in mice showed that angiogenesis in the MWCNT experimental group was significantly reduced. The results of a protein chip analysis indicated that VEGF expression in the MWCNT treatment group was decreased, a finding that was validated by ELISA results. The protein expression levels of AKT and eNOS in the MWCNT treatment group were significantly decreased; the administration of recombinant VEGF significantly alleviated the migration ability and tube formation ability of endothelial cells injured by MWCNTs, upregulated the protein expression of AKT and eNOS, and increased the number of neovascularization in mice in the MWCNT treatment group. This study demonstrated that MWCNTs affect angiogenesis via the VEGF-Akt-eNOS axis which can be rescued by VEGF endothelial treatment.

[Sedimentary Diatom Records Reveal the Succession of Ecosystem in Lake Xihu, Dali over the Past 50 Years].

In recent decades, intense human activities have caused a decline in many lake ecosystems in Yunnan Province, rendering the transformation of the lake from a clear macrophyte-dominated state to a turbid phytoplankton-dominated state. Improved understanding of the ecological changes in lake ecosystem has significant implications for management. In this study, a small lake in Dali Prefecture of Yunnan Province, i.e., Lake Xihu, was selected. Combined with diatom records and physicochemical proxies from the lake sediments, this paper focuses on the long-term ecological changes in Lake Xihu, Dali since the mid-1960s. The results show that the Lake Xihu, Dali has undergone a significant shift in stable states over the past 50 years. Prior to 2000, the benthic-epiphytic species (i.e., Cocconeis placentula, Staurosira construens, Gomphonema angustum, and Achnanthidium minutissimum) dominated in diatom assemblages, indicating oligotrophic conditions; since 2000, benthic-epiphytic species (i.e., Encyonopsis microcephala and Navicula cryptocephala) and planktonic species (i.e., Cyclotella atomus, Cyclotella meneghiniana, Stephanodiscus hantzschii, and Aulacoseira granulata) dominated successively, indicating mesotrophic to eutrophic conditions. Principal component analysis based on the diatom assemblages in temporal scale showed the response of diatoms succession to nutrients. Redundancy analysis also confirmed that nutrient enrichment was the main driving force for the succession of diatom assemblages in Lake Xihu, Dali. In the past 50 years, climate change and human activities (i.e., agricultural reclamation, fertilization, animal husbandry, and fishery) have enhanced the accumulation of nutrients in the lake. The continuous loading of nutrients promoted the propagation of planktonic algae, and also the productivity of the lake, rendering the transformation to a turbid phytoplankton-dominated state.

Metoprolol rescues endothelial progenitor cell dysfunction in diabetes.

Added risk portended by diabetes in addition to hypertension has been related to an amplification of endothelial dysfunction. ß-blockers are widely used for cardiovascular diseases and improve the endothelial function compared with a placebo. However, the effect of ß-blockers on the endothelial progenitor cells (EPCs) function in diabetes is still unknown. Five ß-blockers (metoprolol, atenolol, propranolol, bisoprolol, and nebivolol) were tested in EPC functional screening. Metoprolol improved EPC function significantly among the five ß-blockers and was chosen for the in vivo tests in STZ induced diabetic mice. Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements were performed using the Endo-PAT2000 device in diabetic patients. Metoprolol, but not other ß-blockers, improved EPC function in both tube formation and migration assay. EPC function was significantly decreased in diabetic mice, and metoprolol treatment restored damaged EPC migration capabilities and circulation EPC number. Metoprolol treatment promoted wound healing and stimulated angiogenesis in diabetic mice. Furthermore, metoprolol significantly enhanced eNOS phosphorylation and decreased O2 - levels in EPCs of diabetic mice. In clinical trials, the RH-PAT index was significantly higher in metoprolol-treated versus bisoprolol-treated diabetics. Metoprolol could accelerate wound healing in diabetic mice and improve endothelial function in diabetic subjects, which may be mediated in part by improving impaired EPC function.

Robust and nanostructured chitosan-silica hybrids for bone repair application.

In this study, chitosan-silica hybrids (CSHs) with superior mechanical strength and homogeneous dispersion of nano-sized silica particles were synthesized via a facile sol-gel method aiming for bone regeneration. The effects of varied acidic conditions of sol-gel reaction and inorganic/organic ratios on the performance of the hybrid were investigated. CSHs synthesized under weak acidic conditions (acetic acid, pH 4.0) showed a homogeneous nanostructure and robust strength (maximum compressive strength: 42.6 ± 3.3 MPa and 271 ± 31 MPa in wet and dry forms, respectively). However, those developed under the strong acidic condition (HCl, pH 4.0) and the strong acid condition plus lower pH (HCl, pH 2.8) tended to aggregate and exhibited inferior mechanical properties (compressive strength: 6.3 ± 0.3 MPa in wet form at pH 2.8). Under the latter conditions, the interactions between silica and chitosan were weak. Moreover, the mechanical properties of the CSHs could be tuned in a wide range by conveniently varying the inorganic/organic composition ratio between 50% and 70%. In vitro cytocompatibility study indicated that CSHs were non-cytotoxic. These results suggested that the weak acidic sol-gel process were essential for fabricating chitosan-silica hybrids with high mechanical strength, which had potential to be applied as a bone substitute.

Effects of probiotics and prebiotics on intestinal microbiota in mice with acute colitis based on 16S rRNA gene sequencing.

BACKGROUND: Imbalance of intestinal microbiota was closely related to colitis. Under these circumstances, regulation of enteric flora may be beneficial to the repair of inflammation. We aimed to investigate the effects of probiotics (Bifidobacterium and Lactobacillus), prebiotics and their combination on inflammation, and microflora in mice of acute colitis. METHODS: C57BL/6J mice were divided into six groups randomly (blank control group, model control group, probiotics group, synbiotics group, lactitol group and probiotics + lactitol group). Each group was given 2.5% dextran sulfate sodium drinking water for 5 days other than the blank control group. Except for the model control group, the other four groups were intervened with probiotics, synbiotics (probiotics and inulin), lactitol, and probiotics + lactitol. Mice were sacrificed after 1 week of gavage, and pathologic scores were calculated. The feces of different periods and intestinal mucosa samples were collected to analyze the differences of intestinal microbiota by 16S rRNA sequencing. Differences of two groups or multiple groups were statistically examined through unpaired Student t test and analysis of variance (ANOVA), respectively. ANOVA, Tukey, Anosim, and metastats analysis were used to compare differences of microbiota among different groups. RESULTS: After gavage for 1 week, the pathologic scores of groups with the intervention were significantly lower than those in the model control group, and the difference was statistically significant (P < 0.05). The model control group was higher in the genus of Bacteroides (relative abundance: 0.3679 vs. 0.0099, P = 0.0016) and lower in Lactobacillus (relative abundance: 0.0020 vs. 0.0122, P = 0.0188), Roseburia (relative abundance: 0.0004 vs. 0.0109, P = 0.0157), compared with the blank control group. However, the same phenomenon was not found in groups gavaged with probiotics and lactitol. Compared with model control group, mice with intervention were increased with Bifidobacterium (relative abundance: 0.0172 vs. 0.0039, P = 0.0139), Lachnospiraceae_NK4A136_group (relative abundance: 0.1139 vs. 0.0320, P = 0.0344), Lachnospiraceae_UCG-006 (relative abundance: 0.0432 vs. 0.0054, P = 0.0454), and decreased with Alistipes (relative abundance: 0.0036 vs. 0.0105, P = 0.0207) in varying degrees. The mucosal flora was more abundant than the fecal flora, and genus of Mucispirillum (relative abundance: 0.0207 vs. 0.0001, P = 0.0034) was more common in the mucosa. Lactitol group showed higher level of Akkermansia than model control group (relative abundance: 0.0138 vs. 0.0055, P = 0.0415), probiotics group (relative abundance: 0.0138 vs. 0.0022, P = 0.0041), and synbiotics group (relative abundance: 0.0138 vs. 0.0011, P = 0.0034), while probiotics + lactitol group had more abundant Akkermansia than synbiotics group (relative abundance: 0.0215 vs. 0.0013, P = 0.0315). CONCLUSIONS: Probiotics and prebiotics reduce the degree of inflammation in acute colitis mice obviously. Mice with acute colitis show reduced beneficial genera and increased harmful genera. Supplementation of probiotics and prebiotics display the advantage of increasing the proportion of helpful bacteria and regulating the balance of intestinal microbiota. Lactitol might promote the proliferation of Akkermansia.

Systematic identification of Celastrol-binding proteins reveals that Shoc2 is inhibited by Celastrol.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer. Celastrol exhibits anti-tumor activities in a variety of cancers. However, the effect of Celastrol on human CRC and the underlying mechanisms still need to be elucidated. The present study aimed to use in vitro and in vivo methods to clarify the anti-tumor effect of Celastrol and use protein microarrays to explore its mechanisms. We demonstrated that Celastrol effectively inhibited SW480 CRC cell proliferation. Two weeks of Celastrol gavage significantly inhibited the growth of xenografts in nude mice. A total of 69 candidate proteins were identified in the protein microarray experiment, including the most highly enriched protein Shoc2, which is a scaffold protein that modulates cell motility and metastasis through the ERK pathway. Celastrol significantly inhibited ERK1/2 phosphorylation in cell lines and xenograft tumors. Down-regulation of Shoc2 expression using Shoc2 siRNA also inhibited ERK1/2 phosphorylation. Furthermore, down-regulation of Shoc2 expression also significantly inhibited proliferation, colony formation, and migration functions of tumor cells. In addition, the LD0 of Celastrol by gavage is equal or more than 80 mg/kg in C57 male mice. In summary, we unraveled the anti-CRC function of Celastrol and confirmed for the first time that it inhibited the ERK1/2 pathway through binding to Shoc2.

[The X-Ray Fluorescence Spectrometer Based on Pyroelectric Effect].

Pyroelectric X-ray generator is implemented, and an X-ray fluorescence spectrometer is accomplished by combining the pyroelectric X-ray generator with a high energy resolution silicon drift detector. Firstly, the parameters of the X-ray generator are decided by analyzing and calculating the influence of the thickness of the pyroelectriccrystal and the thickness of the target on emitted X-ray. Secondly, the emitted X-ray is measured. The energy of emitted X-ray is from 1 to 27 keV, containing the characteristic X-ray of Cu and Ta, and the max counting rate is more than 3 000 per second. The measurement also proves that the detector of the spectrometer has a high energy resolution which the FWMH is 210 eV at 8. 05 keV. Lastly, samples of Fe, Ti, Cr and high-Ti basalt are analyzed using the spectrometer, and the results are agreed with the elements of the samples. It shows that the spectrometer consisting of a pyroelectric X-ray generator and a silicon drift detector is effective for element analysis. Additionally, because each part of the spectrometer has a small volume, it can be easily modified to a portable one which is suitable for non-destructive, on-site and quick element analysis.

[Near infrared distance sensing method for Chang'e-3 alpha particle X-ray spectrometer].

Alpha particle X-ray spectrometer (APXS) is one of the payloads of Chang'E-3 lunar rover, the scientific objective of which is in-situ observation and off-line analysis of lunar regolith and rock. Distance measurement is one of the important functions for APXS to perform effective detection on the moon. The present paper will first give a brief introduction to APXS, and then analyze the specific requirements and constraints to realize distance measurement, at last present a new near infrared distance sensing algorithm by using the inflection point of response curve. The theoretical analysis and the experiment results verify the feasibility of this algorithm. Although the theoretical analysis shows that this method is not sensitive to the operating temperature and reflectance of the lunar surface, the solar infrared radiant intensity may make photosensor saturation. The solutions are reducing the gain of device and avoiding direct exposure to sun light.

[Temperature effect correction for Chang'E-3 alpha particle X-ray spectrometer].

Alpha particle X-ray spectrometer (APXS) is one of the payloads of Chang'E-3 lunar rover of China's Lunar Exploration Project. The present paper introduces briefly the components of APXS, how it works and its working environment on the lunar surface. The environmental temperature effect has been studied with simulations and experiments, and the results show that the temperature of the APXS sensor will be varying during the measuring on the lunar surface. And another experiment reveals that the energy resolution becomes worse if the sensor's temperature is varying. In this paper, a correction method based on Pearson's chi-squared test is presented. The method can improve the energy resolution when the sensor's temperature is varying. We have tested the method with the spectra acquired by APXS in the temperature varying period of Temperature Cycling Test, and the results show that the method is efficient and reliable.

[Antioxidant activity and spectroscopic behavior study with DNA of several Salen Mn(II), Eu(III) complexes].

Five kinds of Salen Mn(II) and two kinds of Eu(III) complexes were synthesized. Under the system of NBT/L-methionine, which creates and detects O2*-, the complexes of antioxidant activity were studied, and the conclusion revealed that all Mn(II) complexes have obvious antioxidant activity. The fluorescence study indicated that all the Salen metal complexes could bind with DNA, which shows their potential anticancer activity.