高频聚焦超声声场和温度场的仿真研究*

为探究临床常用的7 MHz高频聚焦超声在多层生物组织中的声传播以及毫秒级时间内的生物传热规律问题,基于Westervelt方程和Pennes传热方程,使用有限元方法建立高频聚焦超声辐照多层组织的非线性热黏性声传播及传热模型。首先分析了线性模型和非线性模型之间的差异,然后在非线性模型下探究换能器的参数对声场和温度场的影响。仿真结果显示：在7 MHz频率下,当换能器输出声功率超过5 W时,声波传播的非线性效应不可忽视(p <0.05);当声功率从5 W增大到15 W时,非线性模型与线性模型预测的温度偏差从20%增加到34.703%;高频聚焦超声波的非线性行为比低频更加显著,基频能量向高次谐波转移的程度增大,声功率为10 W和15 W时4次谐波与基波之比分别达到7.33%和12.12%;高频换能器参数的改变对组织中声场和温度场分布的影响较大,换能器焦距从12 mm减小到11.2 mm,焦点处最高温度增加了77%。结果表明,7 MHz聚焦超声的非线性声传播需要考虑到4次谐波的影响。该文提出的多层组织非线性仿真模型可为高频聚焦超声换能器参数优化及制定安全、有效的术前治疗方案提供理论参考。     

Carbene-catalyzed activation of cyclopropylcarbaldehydes for mannich reaction and δ-lactam formation: remote enantioselecitvity control and dynamic kinetic asymmetric transformation

An N-heterocyclic carbene(NHC)-catalyzed enantioselective Mannich reaction of the remote γ-carbon of cyclopropylcarbaldehydes is disclosed for the first time. Diastereo-and enantiomerically enriched multicyclic δ-lactam compound is afforded as the main product from 8 possible stereo-specific isomers through dynamic kinetic asymmetric transformation(DYKAT) processes. Multiple chiral functional molecules can be afforded from the lactam products through simple protocols with retentions of the optical purities.     

Rutin Inhibits Ox-LDL-Mediated Macrophage Inflammation and Foam Cell Formation by Inducing Autophagy and Modulating PI3K/ATK Signaling

Atherosclerosis (AS) is one of the leading causes of death among the elderly, and is primarily caused by foam cell generation and macrophage inflammation. Rutin is an anti-inflammatory, anti-oxidant, anti-allergic, and antiviral flavonoid molecule, known to have anti-atherosclerotic and autophagy-inducing properties, but its biological mechanism remains poorly understood. In this study, we uncovered that rutin could suppress the generation of inflammatory factors and reactive oxygen species (ROS) in ox-LDL-induced M2 macrophages and enhance their polarization. Moreover, rutin could decrease foam cell production, as shown by oil red O staining. In addition, rutin could increase the number of autophagosomes and the LC3II/I ratio, while lowering p62 expression. Furthermore, rutin could significantly inhibit the PI3K/ATK signaling pathway. In summary, rutin inhibits ox-LDL-mediated macrophage inflammation and foam cell formation by inducing autophagy and modulating PI3K/ATK signaling, showing potential in treating atherosclerosis.     

A Novel Gelatin-Based Sustained-Release Molluscicide for Control of the Invasive Agricultural Pest and Disease Vector Pomacea canaliculata

Pomacea canaliculata, one of the 100 most destructive invasive species in the world, and it is an important intermediate host of Angiostrongylus cantonensis. The molluscicides in current use are an effective method for controlling snails. However, most molluscicides have no slow-release effect and are toxic to nontarget organisms. Thus, these molluscicides cannot be used on a large scale to effectively act on snails. In this study, gelatin, a safe and nontoxic substance, was combined with sustained-release molluscicide and was found to reduce the toxicity of niclosamide to nontarget organisms. We assessed the effects of gelatin and molluscicide in controlling P. canaliculata snails and eggs. The results demonstrated that the niclosamide retention time with 1.0% and 1.5% gelatin sustained-release agents reached 20 days. Additionally, the mortality rate of P. canaliculata and their eggs increased as the concentration of the niclosamide sustained-release agents increased. The adult mortality rate of P. canaliculata reached 50% after the snails were exposed to gelatin with 0.1 mg/L niclosamide for 48 h. The hatching rate of P. canaliculata was only 28.5% of the normal group after the treatment was applied. The sustained-release molluscicide at this concentration was less toxic to zebrafish, which means that this molluscicide can increase the safety of niclosamide to control P. canaliculata in aquatic environments. In this study, we explored the safety of using niclosamide sustained-release agents with gelatin against P. canaliculata. The results suggest that gelatin is an ideal sustained-release agent that can provide a foundation for subsequent improvements in control of P. canaliculata.     

Simultaneous Determination of Six Immunosuppressants in Human Whole Blood by HPLC-MS/MS Using a Modified QuEChERS Method

A high-performance liquid chromatography-tandem mass spectrometry method was established for the simultaneous determination of mycophenolic acid, mycophenolate mofetil, tacrolimus, rapamycin, everolimus and pimecrolimus in human whole blood by optimizing the QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) preparation method. Whole blood was extracted into ethyl acetate, salted out with anhydrous magnesium sulfate, and purified with ethylenediamine-N-propyl silane adsorbent. The supernatant was evaporated under nitrogen until dry and finally reconstituted in methanol. Chromatographic separation was performed on an Agilent Poroshell 120 EC-C18 column in methanol (mobile phase A)-water (optimized for 0.1% acetic acid and 10 mM ammonium acetate, mobile phase B) at a 0.3 mL·min⁻¹ flow rate. Electrospray ionization and positive ion multiple reaction monitoring were used for detection. The time for of analysis was 13 min. The calibration curves range of tacrolimus, rapamycin, everolimus and pimecrolimus were in the range of 1–100 ng·mL⁻¹, mycophenolate mofetil in the range of 0.1–10 ng·mL⁻¹ and mycophenolic acid at 10–1000 ng·mL⁻¹. All correlation coefficients were >0.993. The coefficients of variation (CV, %) for inter-day and intra-day precision were less than 10%, while the spiked recoveries were in the range of 92.1% to 116%. Our method was rapid, sensitive, specific, and reproducible for the simultaneous determination of six immunosuppressants in human whole blood. Importantly, our approach can be used to monitor drug concentrations in the blood to facilitate disease treatment.     

Piezo channels in the urinary system

The Piezo channel family, including Piezo1 and Piezo2, includes essential mechanosensitive transduction molecules in mammals. Functioning in the conversion of mechanical signals to biological signals to regulate a plethora of physiological processes, Piezo channels, which have a unique homotrimeric three-blade propeller-shaped structure, utilize a cap-motion and plug-and-latch mechanism to gate their ion-conducting pathways. Piezo channels have a wide range of biological roles in various human systems, both in vitro and in vivo. Currently, there is a lack of comprehensive understanding of their antagonists and agonists, and therefore further investigation is needed. Remarkably, increasingly compelling evidence demonstrates that Piezo channel function in the urinary system is important. This review article systematically summarizes the existing evidence of the importance of Piezo channels, including protein structure, mechanogating mechanisms, and pharmacological characteristics, with a particular focus on their physiological and pathophysiological roles in the urinary system. Collectively, this review aims to provide a direction for future clinical applications in urinary system diseases.Subject terms: Bladder disease, Bladder cancer, Prostate cancer, Oncogenesis     

Structural and Bonding Properties of AlnC4-/0 (n=2-4) Clusters:Anion Photoelectron Spectroscopy and Theoretical Calculations

We measured the photoelectron spectra of AlnC4-(n=2-4) clusters by using size-selected anion photoelectron spectroscopy.The structures of AlnC4-/0 (n=2-4) clust...     

Anisotropic Superconducting Properties of Kagome Metal CsV_3Sb_5

We systematically measure the superconducting(SC) and mixed state properties of high-quality CsV_3 Sb_5 single crystals with T_c～3.5 K.We find that the upper critical field H_(c2)(T) exhibits a large anisotropic ratio of H_(c2)~(ab)/H_(c2)~c～9 at zero temperature and fitting its temperature dependence requires a minimum two-band effective model.Moreover,the ratio of the lower critical field,H_(c1)~(ab)/H_(c1)~c,is also found to be larger than 1,which indicates that the in-plane energy dispersion is strongly renormalized near Fermi energy.Both H_(c1)(T) and SC diamagnetic signal are found to change little initially below T_c～3.5 K and then to increase abruptly upon cooling to a characteristic temperature of ～2.8 K.Furthermore,we identify a two-fold anisotropy of in-plane angular-dependent magnetoresistance in the mixed state.Interestingly,we find that,below the same characteristic T～2.8 K,the orientation of this two-fold anisotropy displays a peculiar twist by an angle of 60° characteristic of the Kagome geometry.Our results suggest an intriguing superconducting state emerging in the complex environment of Kagome lattice,which,at least,is partially driven by electron-electron correlation.     

Luminescence interference-free lifetime nanothermometry pinpoints in vivo temperature

Luminescence nanothermometry makes non-invasive and real-time temperature readings possible in living animals. However,the spectral fluctuation in tissues and fluids, as well as the interaction between fluorophores and environment hinders accuracy of the thermometry. Here, we report a luminescence lifetime-based nanothermometry which specifically addresses this problem. A temporal based calibration(lifetime sensing) in the NIR range, an endogenous thermal response as well as a polymer encapsulation evading environmental factors, altogether help to pinpoint temperature in vivo. Thanks to the highly condensed NdYb ions in a well-protected tiny core-shell nanocrystal(overall 11 nm), a temperature sensitivity about 2.07% K~(-1)(with 5% Yb~(3+) doped nanoparticles) and an accuracy of 0.27 K(with 25% Yb~(3+) doped nanoparticles) in biological fluids are achieved.Hopefully, combining thermally activated energy transfer nanothermometer with anti-interference lifetime thermometry would provide a more accurate temperature measurement for biological and preclinical studies.