G6PD inhibits ferroptosis in hepatocellular carcinoma by targeting cytochrome P450 oxidoreductase.

Ferroptosis is an important cell necrosis and has been a focus in cancer related research.Increcsing studies have focused on the phenotype and function of ferroptosis in tumorigenesis, but the underlying mechanism remains poorly understood. Here, we used bioinformatics approaches to identify differentially expressed genes associated with HCC and ferroptosis. We found that G6PD (glucose-6-phosphate dehydrogenase) was highly expressed in HCC and was associated with poor prognosis. G6PD promoted the proliferation, migration and invasion, as well as inhibited ferroptosis in HCC cells. Pathway and functional enrichment analyses revealed that G6PD was related to the P450 metabolic pathway. POR (cytochrome P450 oxidoreductase) was downregulated in HCC and was significantly correlated with the prognosis. G6PD inhibited ferroptosis inin HCC cells through POR. Knockdown of G6PD reduced the tumor volume and tumor weight in vivo. Our study demonstrated that G6PD deficiency suppresses cell growth, metastasis, and tumorigenesis via upregulating POR, suggesting that G6PD may be used as a biomarker for the treatment of HCC in the future.

A new contrast-to-noise ratio for image quality characterization of a coded-aperture γ camera.

The gamma-ray imaging technique was developed and is widely used in several nuclear engineering fields. Specifically, compared with the traditional point-by-point radiation detector, the coded-aperture gamma camera has advantages of a wide field of view, high angular resolution, and high efficiency. Several methods for characterizing image quality, including the figure of merit (FOM) method and the contrast-to-noise ratio (CNR) method, were assessed and developed. These methods have their respective drawbacks depending on the circumstances. The FOM lacks reliability in exhibiting the impact of background noise fluctuation on the purity of a real image. The CNR characterizes image quality with inconsistent sensitivity while the source moves along the X and Y directions. Therefore, a new CNR method was proposed to achieve better performance and greater consistency in real imaging. With our coded-aperture imaging system developed in the laboratory, we performed simulations within the MATLAB and Geant4 platforms and real imaging experiments to analyze and compare images and the results of these three characterization methods. The results show that the new CNR method is reliable and practical in regard to real imaging performance.

Design of an Am-Be neuron source experimental platform at Sichuan University.

Am-Be neutron sources are widely used in nuclear laboratories. It is important to design adequate shielding for Am-Be neutron sources, in order to protect experimenters from being irradiated by neutrons and their associated γ-rays. When designing shielding, it is also much desired for the source assembly to provide sufficient neutron moderation, and furnish access channels for both thermal and fast neutrons directly from the source. Such a neutron source assembly may be called a "neutron source experimental platform". This paper presents the design details of an Am-Be neutron source experimental platform at Sichuan University. The experimental platform is designed to be a Φ 100 cm × 100 cm paraffin cylinder with the Am-Be source at the center. The paraffin cylinder is inside a 0.5 cm thick stainless-steel container lined with 2 cm thick borated polyethylene. The platform has multiple access channels for thermal neutrons, and one access channel for fast neutrons. The design calculations were performed with Geant4.

Development of an isocentric rotating chair positioner to treat patients of head and neck cancer at upright seated position with multiple nonplanar fields in a fixed carbon-ion beamline.

PURPOSE: An isocentric rotating chair for a positioner was developed as a nongantry solution to provide multiple nonplanar radiation fields with a maximum tilt of 20 ∘ for treating head and neck cancer patients at an upright seated position in a fixed carbon-ion beamline. METHODS: The preclinical validation of the chair was present for this study funded by a grant through the Shanghai Proton and Heavy Ion Center (SPHIC) in Shanghai, China. The chair was installed in SPHIC. A concept of parallel kinematic was adopted to build the chair. Three movement subunits of the chair are a Stewart hexapod platform and two modules for three-dimensional translation and 360 ∘ rotation. This chair can position patients with a tilt up to 20 ∘ over a continuous 360 ∘ rotation. Any weak structures within each subunit were investigated by industrial static/dynamic simulations of used materials. After manufactured subunits were assembled in a factory, a series of executed six degree-of-freedom (DoF) displacements were measured by using a laser-based dynamic tracking system (LDTS) for the initial validation. Deviations between measured and required displacements, referred to as displacement deviation, were used to evaluate the displacement accuracy of the chair. After satisfying the initial validation in the factory, the chair was disassembled and installed in our treatment room. The displacement accuracy of the chair was revalidated by using the LDTS. Then, an integration validation of the chair was conducted to position a head phantom by using our image-guided radiotherapy (IGRT) system. Because the positioning accuracy of our IGRT system achieved a clinical tolerance of 1.0 mm and 1.0 ∘ only for a pitch/roll of <5 ∘ , the integration validation was conducted on 36 planned fields with a 5 ∘ tilt evenly over 360 ∘ rotation. RESULTS: To fulfill the general purpose of positioner, the chair allows the execution of any displacement over a cubic treatment volume with a length of 500 mm. Materials selected by simulations met required strengths under all circumstances of the clinical usage. The displacement accuracy of the chair satisfied the tolerance of 0.3 mm in-translation and 0.3 ∘ in-rotation during the initial validation in the factory. After the chair was installed in our institute, a linear displacement deviation of +/-0.6 mm was observed over +/-200 mm displacements in horizontal X/Y axes. After correcting the linear deviation, the displacement deviations of the chair for horizontal and vertical X/Y/Z axes were within 0.5 mm and 0.5 ∘ for its revalidation. During the integration validation, the displacement deviation of the chair was 0.8 mm and 0.6 ∘ when positioning a head phantom for the 36 fields with a 5 ∘ tilt. CONCLUSIONS: The chair achieved the required clinical tolerance for the clinical application. The tilt angle was limited to within 5 ∘ to treat patients through a specific treatment workflow with a proper daily quality assurance program during a clinical trial, started in May 2019. An integration validation with a 20 ∘ tilt will be conducted in the near future to realize the full potential of the isocentric rotating chair.

Generation of a human control PBMC derived iPS cell line TUSMi001-A from a healthy male donor of Han Chinese genetic background.

A 59-year old healthy man of Han Chinese genetic background donated his peripheral blood mononuclear cells (PBMC). The non-integrating episomal vector system was used to reprogram his PBMCs with the human OSKM (Oct4, Sox2, Kl4 and c-Myc) transcription factors. The pluripotency of transgene-free iPSCs was confirmed by immunocytochemistry for pluripotency markers and by the ability of the iPSCs to differentiate spontaneously into 3 germ layers in vitro. In addition, the iPSC line displayed a normal karyotype. In the studies of disease mechanism, the iPSC line can be used as a control.

Study of sampling rate influence on neutron-gamma discrimination with stilbene coupled to a silicon photomultiplier.

Choosing a digitizer with an appropriate sampling rate is often a trade-off between performance and economy. The influence of sampling rates on the neutron-gamma Pulse Shape Discrimination (PSD) with a solid stilbene scintillator coupled to a Silicon Photomultiplier was investigated in this work. Sampling rates from 125MSPS to 2GSPS from a 10-bit digitizer were used to collect detector pulses produced by the interactions of a Cf-252 source. Due to the decreased signal-to-noise ratio (SNR), the PSD performance degraded with reduced sampling rates. The reason of PSD performance degradation was discussed. Then, an efficient combination of filtering and digital signal processing (DSP) was then applied to suppress the timing noise and electronic background noise. The results demonstrate an improved PSD performance especially at low sampling rates, down to 125MSPS. Using filtering and DSP, the ascribed Figure of Merit (FOM) at 125keVee (± 10keVee) increased from 0.95 to 1.02 at 125MSPS. At 300keVee and above, all the FOMs are better than 2.00. Our study suggests that 250MSPS is a good enough sampling rate for neutron-gamma discrimination in this system in order to be sensitive to neutrons at and above ~ 125keVee.

Design, development and evaluation of a resistor-based multiplexing circuit for a 20×20 SiPM array.

One technical challenge in developing a large-size scintillator detector with multiple Silicon Photomultiplier (SiPM) arrays is to read out a large number of detector output channels. To achieve this, different signal multiplexing circuits have been studied and applied with different performances and cost-effective tradeoffs. Resistor-based multiplexing circuits exhibit simplicity and signal integrity, but also present the disadvantage of timing shift among different channels. In this study, a resistor-based multiplexing circuit for a large-sized SiPM array readout was developed and evaluated by simulation and experimental studies. Similarly to a multiplexing circuit used for multi-anode PMT, grounding and branching resistors were connected to each SiPM output channel. The grounding resistor was used to simultaneously reduce the signal crosstalk among different channels and to improve timing performance. Both grounding and branching resistor values were optimized to maintain a balanced performance of the event energy, timing, and positioning. A multiplexing circuit was implemented on a compact PCB and applied for a flat-panel detector which consisted of a 32×32 LYSO scintillator crystals optically coupled to 5×5 SiPM arrays for a total 20×20 output channels. Test results showed excellent crystal identification for all 1024 LYSO crystals (each with 2×2×30 mm3 size) with 22Na flood-source irradiation. The measured peak-to-valley ratio from typical crystal map profile is around 3:1 to 6.6:1, an average single crystal energy resolution of about 17.3%, and an average single crystal timing resolution of about 2 ns. Timing shift among different crystals, as reported in some other resistor-based multiplexing circuit designs, was not observed. In summary, we have designed and implemented a practical resistor-based multiplexing circuit that can be readily applied for reading out a large SiPM array with good detector performance.

Natural and artificial radionuclide measurements and radioactivity assessment of soil samples in eastern Sichuan province (China).

The activity concentrations of natural and artificial radionuclides were measured in the eastern region of Sichuan province (China). One hundred and ninety-three soil samples from this region were collected and analysed by high-purity germanium gamma spectrometry. The measured results show that the average radioactivity concentrations of (226)Ra, (232)Th, (40)K and (137)Cs in the soil samples are 26, 49, 440 and 6 Bq kg(-1), respectively. The calculated average radium equivalent activity is 130 Bq kg(-1), which is less than the recommended limit of 370 Bq kg(-1). The absorbed dose rate and annual effective dose are 60 nGy h(-1) and 74 µSv, respectively. This is the first time the absorbed dose rate in the east region of Sichuan has been mapped. Overall, the environmental radiation background is greater in the southern part of the area studied than in the northern.

Protective effects of inosine on mice subjected to lethal total-body ionizing irradiation.

Mammals can barely survive total-body ionizing irradiation greater than 10 Gy. To date, there are few drugs available for radioprotective therapy under such circumstances. Inosine, a natural derivative of adenosine, has been known to provide powerful protection for many kinds of cells and tissues against various insults both in vitro and in vivo. In the present study, we examined whether inosine was also beneficial for mammals subjected to an absolutely lethal total-body ionizing irradiation. Immediately after adult Balb/c mice were exposed to (60)Co gamma-rays at a single dose of 12 Gy, a moiety of them were administered daily with inosine or adenosine, either at doses of 375 or 750 micromol/kg up to death, and their body weight and survival time were recorded. Some irradiated mice were administered inosine or adenosine daily at doses of 750 micromol/kg and assessed for spatial memory abilities using the Morris water maze. The results demonstrated that, although inosine could not prevent body weight loss in irradiated mice, it was able to significantly prolong their survival time at doses of 750 micromol/kg. Moreover, inosine but not adenosine could suppress spatial memory deficit in irradiated mice. The data suggested that inosine had protective effects on mammals suffering from total-body ionizing irradiation at a single lethal dose.