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Liver tumor-initiating cells (TICs) are involved in liver tumorigenesis, metastasis, drug resistance and relapse, but the regulatory mechanisms of liver TICs are largely unknown. Here, we have identified a functional circular RNA, termed circRNA activating MAFF (cia-MAF), that is robustly expressed in liver cancer and liver TICs. cia-MAF knockout primary cells and cia-maf knockout liver tumors harbor decreased ratios of TICs, and display impaired liver tumorigenesis, self-renewal and metastatic capacities. In contrast, cia-MAF overexpression drives liver TIC propagation, self-renewal and metastasis. Mechanistically, cia-MAF binds to the MAFF promoter, recruits the TIP60 complex to the MAFF promoter, and finally promotes MAFF expression. Loss of cia-MAF function attenuates the combination between the TIP60 complex and the MAFF promoter. MAFF is highly expressed in liver tumors and liver TICs, and its antisense oligo (ASO) has therapeutic potential in treating liver cancer without MAFA/MAFG gene copy number alterations (CNAs). This study reveal an additional layer for liver TIC regulation as well as circRNA function, and also provide an additional target for eliminating liver TICs, especially for liver tumor without MAFA/MAFG gene CNAs.

Rapid and effective determination of biomechanical properties is important in examining and diagnosing skin thermal injury. Among the methods used, viscoelasticity quantification is one of the most effective methods in determining such properties. This study aims to rapidly determine skin viscoelasticity by optically tracking the local surface wave. New elastic and viscous coefficients were proposed to indicate skin viscoelasticity based on a single impulse response of the skin. Experiments were performed using fresh porcine skin samples. Surface wave was generated in a single impulse using a vibrator with a ball-tipped device and was detected using a laser Doppler vibrometer. The motions along the depth direction were monitored using an ultrasound system. The ultrasound monitoring results indicated the multi-layered viscoelasticity of the epidermis and dermis. The viscoelastic coefficients from four healthy samples show a potential viscoelasticity variation of porcine skin. In one sample, the two coefficients were evidently higher than those in a healthy area if the skin was slightly burned. These results indicate that the proposed method is sensitive, effective, and quick in determining skin viscoelasticity.

A novel approach combining dual frequency and split focus approaches is proposed to substantially enhance heating in treatment by using a prototype broadband splitfocus transducer. Using a dual-frequency mode in which the higher frequency is twice the lower frequency, the superimposition of two frequency pressures in the confocal region can enhance nucleation cavitation and inertial cavitation activity. Ex vivo liver or gel phantom experiments using the dual frequencies of 1.2 and 2.4 MHz confirmed a lesion size about two times larger than that obtained using a single 1.6 MHz frequency. The mean square indicating inertial cavitation energy from filtered passive cavitation detection (PCD) data demonstrated that the inertial cavitation activity dominated the enhanced heating rate and that the extra frequency components in the dual-frequency case contributed to increasing the lesion size. The dual-frequency, split-focus protocol takes great advantages of temporally and spatially enhanced-cavitation heating. The results revealed that the dual-frequency, split-focus method enhanced the heating rate one order of magnitude more than other methods. The inertial cavitation energy waveform revealed that the strong inertial cavitation action was involved in enhanced heating in the entire 22 s treatment. The greater spatial area of preformed bubble-layer surface reflection (or scatter ultrasound) regime in the dual-frequency, split-focus protocol enhanced the proximal acoustic field and enlarged the enhanced-pressure field toward the transducer about 3 times in the axial original-focal dimension, as well as laterally. This regime supported the sustained inertial cavitation during a 22 s treatment. An increased pulse-repetition frequency (PRF) protocol was formed using dual frequency and split focus, increasing PRF from 1 to 10, 20, and 40 Hz to take advantage of pulse-induced cavitation. The experiments demonstrated that the lesion size with 20 Hz PRF was about 2.5 times that obtained with 1 Hz PRF, and possessed quick 0.2 s lesioninception time. Within the high-frequency band, the inertialcavitation frequency integral was approximately proportional to the lesion size of 1, 10, 20, and 40 Hz PRF respectively, indicating higher frequency contribution to enhanced heating.

A plasma jet ignition technology was studied for aeroengine combustor. The advantages of compact structure and advanced performance of air-cooled plasma jet igniter had been tested and verified in the opening test. The plasma jet igniter could produce a continuous plasma jet, stable and reliable ignition. The influence factors of plasma jet ignition aerodynamic and structure were studied in the opening test. Continuous plasma jet was closely related to inlet pressure and flow, simultaneously to the igniter nozzle geometry and throat size. Based on the stable continuous plasma jet, some methods were explored in order to reduce plasma output power, optimize the structure design, and improve the thermal protective. The plasma jet igniter applied to aeroengine combustor was identified initially. For combustion chamber with the igniter, altitude ignition performance were experimented for the inlet pressure of plasma ignition from 10 kPa to 50 kPa, the flow of plasma jet not more than 0.20 g/s, and energy output of ignition from 800 W to 1500 W. The test results were compared with that of conventional aeroengine high energy ignition system. The results show that the plasma jet igniter is better than the conventional one.

To substantially enhance heating in HIFU treatment, several methods such as split foci, multi foci, and dual-frequency modes are used. The enhanced-cavitation heating protocols are implemented experimentally in BSA gel-phantom using four-element split-focus array. Using dual frequency of 1.2 and 2.4 MHz, the superimposing of two frequency pressures at confocal region can enhance nucleation cavitation and inertial cavitation activity. When using 135° phase shift combined with dual frequency of 1.2 and 2.4 MHz, the peak negative pressure reach maximum due to peak-negative pressures of two frequencies occur at same time, resulting strong cavitation activities. When using dual frequency of 1.2 and 2.4 MHz, 25-Hz pulse-repetition frequency (PRF), both 135° and 180° phase shift protocols, the experiment results show the largest lesion size of 10.5 × 10.5 × 11 mm3, quickest lesion inception time of less than 0.2 s, therefore, both 135° and 180° phase shift protocols are most efficient in enhanced-cavitation heat...

A two-stage treatment was performed to explore the feasibility of generating histotripsy using hundred-microsecond pulses. A single-element 1.06-MHz transducer was used at 8 MPa peak negative pressure with shockwaves. Stage 1 was performed to accelerate the rupture of local tissue structure by boiling bubbles. The pulse group had 500-µs/400-µs pulse duration (PD) and 100-Hz pulse repetition frequency (PRF) with 4.9%/3.9% duty cycle (DC). Stage 2 involved the mechanical homogenization of the lesion by inertial cavitation. Several locations in the lesion axial direction were treated simultaneously by the bubble clusters induced by multiple reflection of shocks. The pulse group had 500-µs/400-µs PD with 100-Hz PRF and 200-µs PD with 200-Hz PRF with 1%/0.88% DC. Experiments were conducted on polyacrylamide phantoms with bovine serum albumin and on rabbit liver tissues ex vivo. Final lesions had a cylindrical shape with smooth borders and total homogenate inside. These results demonstrated that hundred-microsecond pulses enabled controllable histotripsy with a lower acoustic pressure.

This study aims at enhancing cavitation heating by using dual-frequency modes of second-harmonic and third-harmonic superimposition for high-efficient focused-ultrasound surgery. By controlling the ratio of dual-frequency acoustic powers, the superimposing of two frequency pressures result in split foci along beam axial within confocal region, and the maximal peak intensity of split focus can reach about 2 times the sum of two frequency intensities, indicating strong wave interference. The 1.1 MHz/3.3 MHz and 1.1 MHz/2.2 MHz experiments implemented in BSA gel-phantom, and lesion inception time is about 0.3 s, which is 10 times shorter than that in single frequency mode. The boiling bubbles occur frequently in each lesion formation, beneficiating increase the lesion size. In 1.1 MHz/3.3 MHz modes, lesions developed in a symmetrical manner in ellipsoid shapes. The 12-s lesion size of 1.1 MHz/3.3 MHz modes is nearly two times as large as the lesion size of 1.1 MHz/2.2 MHz modes. Although in 20% DC case, the acoustic power dose is only a half that used in 80% DC case, the 12-s lesion size with 20% DC is nearly same as that with 80% DC for both 1.1 MHz/3.3 MHz and 1.1 MHz/2.2 MHz conditions. The inertial-cavitation-energy waveforms reveal that the strong inertial-cavitation activities involve in all cases.

A new strategy is proposed in this study to rapidly generate mechanical homogenized lesions using hundred-microsecond-long pulses. The pulsing scheme was divided into two stages: generating sufficient bubble seed nuclei via acceleration by boiling bubbles and efficiently forming a mechanically homogenized and regularly shaped lesion with a homogenate inside via inertial cavitation. The duty cycle was set at 4.9%/3.9% in stage 1 and 1%/0.88% in stage 2 by changing the pulse duration (PD) and off-time independently. The pulse sequence was 500-μs/400-μs PD with a 100-Hz pulse repetition frequency (PRF) in stage 1, followed by 500-μs/400-μs PD with a 100-Hz PRF and 200-μs PD with a 200-Hz PRF in stage 2. Experiments were conducted on polyacrylamide phantoms with bovine serum albumin and on ex vivo porcine kidney tissues using a single-element 1.06-MHz transducer at an 8-MPa peak negative pressure with shock waves. The lesion evolution and dynamic elastic modulus variation in the phantoms and the histology in the tissue samples were investigated. The results indicate that the two-stage treatment using hundred-microsecond-long pulses can efficiently produce mechanically homogenized lesions with smooth borders, long tear shapes and the total homogenate inside. The time to generate a single mechanically homogenized lesion is shortened from >50 s to 17.1 s.

Purpose. To investigate the correlation between aqueous and serum levels of pigment epithelium-derived factor (PEDF) and macular choroidal thickness in high myopia patients, both with and without choroidal neovascularization (CNV).Methods. Serum and aqueous levels of PEDF were measured by enzyme-linked immunosorbent assay in 36 high myopia patients (36 eyes) with no CNV (non-CNV group), 14 high myopia patients (14 eyes) with CNV (CNV group), and 42 nonmyopia patients (42 eyes) (control group). Macular choroidal thickness was measured by enhanced-depth imaging optical coherence tomography.Results. Aqueous levels of PEDF were significantly higher in CNV group compared with non-CNV (P<0.001) and control (P<0.001) groups. Macular choroidal thicknesses were significantly decreased in the non-CNV and CNV groups compared with the control (P<0.001) group. A statistically significant difference (P=0.012) was found between the CNV and non-CNV groups. There was a positive correlation between aqueous PEDF and macular choroidal thickness in the non-CNV group (P=0.005), but no correlation with the CNV group. No correlation between serum PEDF and macular choroidal thickness was detected in the three groups.Conclusion. Variations in aqueous PEDF levels coincide with changes in macular choroidal thickness in high myopia patients with no CNV, while no such relationship exists in high myopia patients with CNV.

A Monte Carlo method of multiple scattered coherent light with the information of shear wave propagation in scattering media is presented. The established Monte-Carlo algorithm is mainly relative to optical phase variations due to the acoustic-radiation-force shear-wave-induced displacements of light scatterers. Both the distributions and temporal behaviors of optical phase increments in probe locations are obtained. Consequently, shear wave speed is evaluated quantitatively. It is noted that the phase increments exactly track the propagations of shear waves induced by focus-ultrasound radiation force. In addition, attenuations of shear waves are demonstrated in simulation results. By using linear regression processing, the shear wave speed, which is set to 2.1 m/s in simulation, is estimated to be 2.18 m/s and 2.35 m/s at time sampling intervals of 0.2 ms and 0.5 ms, respectively.

We concentrate on the nondissipative mechanism induced shear wave in inhomogenous tissue. The shear wave equation of radiation force in inhomogeneous media is solved numerically with a finite-difference time-domain method. A rarely studied nondissipative mechanism of shear displacement due to a smooth medium inhomogeneity is evaluated. It is noted that unlike the dissipative effect, the nondissipative action on a localized inhomogeneity with its hardness parameter changing smoothly along the beam axis, compresses or stretches the focus area. The shear waves in nondissipative inhomogeneous media remain the property of sharp turn with 100% peak positive displacement and 64% peak negative displacement. This action is useful in discerning the water-like lesion.