Research on Inherent Frequency and Vibration Characteristics of Sandwich Piezoelectric Ceramic Transducer.

Great progress has been made in the field of ultrasonic processing in recent years, and piezoelectric ceramic transducers have been widely used as drive sources. In this paper, a sandwich piezoelectric ceramic transducer is designed, and the vibration of each part of the transducer is analyzed by elastic mechanics and piezoelectric theory. According to its mechanical and electrical boundary conditions, the vibration model of the piezoelectric transducer was established. Based on the equivalent elastic modulus method for simplifying the pre-stressed bolts into a one-dimensional transducer vibration model, the relationship between the one-dimensional axial response frequency of the transducer and the length of each component was obtained. Based on the half wavelength theory, a transducer with the vibration node in the crystal stack and an inherent frequency of 15 kHz was designed and fabricated. In order to verify the natural frequency and vibration characteristics of the piezoelectric transducer, a laser vibration measurement system was built in this study. The vibration characteristics of the transducer under different parameters such as voltage and frequency were analyzed, and the accuracy of the vibration model was verified. The vibration states of the end surface of the transducer and the radial surface were evaluated at the first-order inherent frequency and second-order inherent frequency. The results show that the equivalent simplified model established in this study can effectively design the inherent frequency of the transducer, and the operation at the first-order inherent frequency meets the one-dimensional assumptions of this study. The transducer operating conditions measured in this study also provide a more detailed reference for ultrasonic processing applications.

Sequentially sustained release of anticarcinogens for postsurgical chemoimmunotherapy.

Postsurgical treatment is of great importance to combat tumor recurrence and metastasis. Anti-CD47 antibodies (aCD47) can block the CD47-signal regulatory protein-alpha (CD47-SIRPα) pathway to restore immunity. Here, an in-situ gel implantation was engineered by crosslinking chitosan (CS) and pullulan (Pul) for postsurgical treatment. A highly selected chemotherapeutic, cyclopamine (Cyc), encapsulated in liposomes (Cyc-Lip) was co-loaded with aCD47 in gels for chemoimmunotherapy. Importantly, a sequential drug release kinetics can be achieved. Nanotherapeutics were confirmed to be released prior to aCD47 in a burst-release manner, which was benefit for immediately killing residual tumor cells followed by releasing tumor antigens. Meanwhile, aCD47 was released in a sustained-release manner to restore macrophage functions and exert anti-tumor immune responses. Afterwards, the efficacy of in-situ chemoimmunotherapy was confirmed on 4T1 mouse breast cancer models, which could not only efficiently augment anti-tumor effect to inhibit tumor recurrence but also establish a long-term immune memory to combat tumor metastasis.

Intranasal delivery of icariin via a nanogel-thermoresponsive hydrogel compound system to improve its antidepressant-like activity.

Although icariin has been reported to have antidepressant-like effects in different animal models, its poor oral bioavailability and low efficiency of delivery to the brain limit its application. In this study, icariin nanogels were prepared by reverse microemulsion methods to improve its poor water solubility. Then, we developed an icariin nanogel loaded self-assembled thermosensitive hydrogel system (icariin-NGSTH) to deliver icariin via a noninvasive, direct nose-to-brain delivery route for the treatment of depression. The in vivo distribution was investigated by fluorescence imaging with rhodamine B-labeled nanogels. The antidepressant efficacy of icariin-NGSTH was evaluated in behavioral despair tests and the chronic unpredictable mild stress (CUMS) model. The results showed that icariin-NGSTH had a zero-order kinetics release in the first 10 h. Icariin-NGSTH led to rapid brain distribution within 30 min. Icariin-NGSTH significantly reduced the duration of immobility in the tail suspension test (TST) and forced swim test (FST). Compared with oral administration, intranasally administered icariin-NGSTH had a fast-acting antidepressant effect in the TST and FST. Moreover, icariin-NGSTH increased body weight and sucrose preference, reversed abnormal plasma levels of testosterone, interleukin-6 (IL-6) and prostaglandin E2 (PGE2), and repaired neuronal damage in the hippocampi of CUMS rats. These results indicated that icariin-NGSTH at a low dose produced a significant antidepressant effect. As a complex drug delivery system, intranasally administered icariin-NGSTH is a rapid and effective treatment for depression, increasing the antidepressant-like activity of icariin.

Dan-Lou Prescription Inhibits Foam Cell Formation Induced by ox-LDL via the TLR4/NF-κB and PPARγ Signaling Pathways.

Atherosclerosis is the major worldwide cause of mortality for patients with coronary heart disease. Many traditional Chinese medicine compound prescriptions for atherosclerosis treatment have been tried in patients. Dan-Lou prescription, which is improved from Gualou-Xiebai-Banxia decoction, has been used to treat chest discomfort (coronary atherosclerosis) for approximately 2,000 years in China. Although the anti-inflammatory activities of Dan-Lou prescription have been proposed previously, the mechanism remains to be explored. Based on the interaction between inflammation and atherosclerosis, we further investigated the effect of Dan-Lou prescription on macrophage-derived foam cell formation and disclosed the underlying mechanisms. In the oxidative low-density lipoprotein (ox-LDL) induced foam cells model using murine macrophage RAW 264.7 cells, the ethanol extract from Dan-Lou prescription (EEDL) reduced ox-LDL uptake and lipid deposition by inhibiting the protein and mRNA expression of Toll-like receptor (TLR)4 and scavenger receptor (SR)B1. After stimulation with ox-LDL, the metabolic profile of macrophages was also changed, while the intervention of the EEDL mainly regulated the metabolism of isovalerylcarnitine, arachidonic acid, cholesterol, aspartic acid, arginine, lysine, L-glutamine and phosphatidylethanolamine (36:3), which participated in the regulation of the inflammatory response, lipid accumulation and cell apoptosis. In total, 27 inflammation-related gene targets were screened, and the biological mechanisms, pathways and biological functions of the EEDL on macrophage-derived foam cells were systemically analyzed by Ingenuity Pathway Analysis system (IPA). After verification, we found that EEDL alleviated ox-LDL induced macrophage foam cell formation by antagonizing the mRNA and protein over-expression of PPARγ, blocking the phosphorylation of IKKα/ß, IκBα and NF-κB p65 and maintaining the expression balance between Bax and Bcl-2. In conclusion, we provided evidences that Dan-Lou prescription effectively attenuated macrophage foam cell formation via the TLR4/NF-κB and PPARγ signaling pathways.

The Combination of icariin and constrained dynamic loading stimulation attenuates bone loss in ovariectomy-induced osteoporotic mice.

Osteoporosis is a disease characterized by low bone mass and progressive destruction of bone microstructure, resulting in increasing the risk of fracture. Icariin (ICA) as a phytoestrogen shows osteogenic effects, and the mechanical stimulation has been demonstrated the improving effect on osteoporosis. The objective of this study was to investigate the effect of ICA in combination with constrained dynamic loading (CDL) stimulation on osteoporosis in ovariectomized (OVX) mice. The serum hormone levels, bone turnover markers, trabecular architecture, ulnar biomechanical properties, and the expression of osteoblast-related gene (alkaline phosphatase, ALP; osteocalcin, OCN; bone morphogenetic protein-2, BMP-2; Collagen I (α1), COL1; osteoprotegerin, OPG) and osteoclast-related genes (receptor activators of NF-κB ligand, RANKL; tartrate-resistant acid phosphatase, TRAP) were analyzed. The results showed that ICA + CDL treatment could increase the osteocalcin (20.85%), estradiol levels (20.61%) and decrease the TRAP activity (26.27%) significantly than CDL treatment. The combined treatment attenuated bone loss and biomechanical decrease more than single use of CDL treatment. ICA + CDL treatment significantly up-regulated the level of osteoblast-related gene expression and down-regulated the osteoclast-related genes expression; moreover, the combined treatment increased the ratio of OPG/RANKL significantly compared to ICA (72.83%) or CDL (65.63%) treatment alone. The present study demonstrates that icariin in combination with constrained dynamic loading treatment may have a therapeutic advantage over constrained dynamic loading treatment alone for the treatment of osteoporosis, which would provide new evidence for the clinical treatment of osteoporosis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1415-1424, 2018.