In Situ Observation of Dark Current Emission in a High Gradient rf Photocathode Gun.

Undesirable electron field emission (also known as dark current) in high gradient rf photocathode guns deteriorates the quality of the photoemission current and limits the operational gradient. To improve the understanding of dark current emission, a high-resolution (∼100 µm) dark current imaging experiment has been performed in an L-band photocathode gun operating at ∼100 MV/m of surface gradient. Scattered strong emission areas with high current have been observed on the cathode. The field enhancement factor ß of selected regions on the cathode has been measured. The postexaminations with scanning electron microscopy and white light interferometry reveal the origins of ∼75% strong emission areas overlap with the spots where rf breakdown has occurred.

Tunable High-Intensity Electron Bunch Train Production Based on Nonlinear Longitudinal Space Charge Oscillation.

High-intensity trains of electron bunches with tunable picosecond spacing are produced and measured experimentally with the goal of generating terahertz (THz) radiation. By imposing an initial density modulation on a relativistic electron beam and controlling the charge density over the beam propagation, density spikes of several-hundred-ampere peak current in the temporal profile, which are several times higher than the initial amplitudes, have been observed for the first time. We also demonstrate that the periodic spacing of the bunch train can be varied continuously either by tuning launching phase of a radio-frequency gun or by tuning the compression of a downstream magnetic chicane. Narrow-band coherent THz radiation from the bunch train was also measured with µJ-level energies and tunable central frequency of the spectrum in the range of ∼0.5 to 1.6 THz. Our results pave the way towards generating mJ-level narrow-band coherent THz radiation and driving high-gradient wakefield-based acceleration.

Observation of Field-Emission Dependence on Stored Energy.

Field emission from a solid metal surface has been continuously studied for a century over macroscopic to atomic scales. It is general knowledge that, other than the surface properties, the emitted current is governed solely by the applied electric field. A pin cathode has been used to study the dependence of field emission on stored energy in an L-band rf gun. The stored energy was changed by adjusting the axial position (distance between the cathode base and the gun back surface) of the cathode while the applied electric field on the cathode tip is kept constant. A very strong correlation of the field-emission current with the stored energy has been observed. While eliminating all possible interfering sources, an enhancement of the current by a factor of 5 was obtained as the stored energy was increased by a factor of 3. It implies that under certain circumstances a localized field emission may be significantly altered by the global parameters in a system.

Gallic acid enhances anti-lymphoma function of anti-CD19 CAR-T cells in vitro and in vivo.

Chimeric antigen receptor T (CAR-T) cell targeting CD19 antigen has achieved exhilarative clinical efficacy in B-cell malignancies. However, challenges still remain for the currently approved anti-CD19 CAR-T therapies, including high recurrence rates, side effects and resistance. Herein, we aim to explore combinatorial therapy by use of anti-CD19 CAR-T immunotherapy and gallic acid (GA, an immunomodulatory natural product) for improving treatment efficacy. We assessed the combinatorial effect of anti-CD19 CAR-T immunotherapy with GA in cell models and a tumor-bearing mice model. Then, the underlying mechanism of GA on CAR-T cells were investigated by integrating network pharmacology, RNA-seq analysis and experimental validation. Furthermore, the potential direct targets of GA on CAR-T cells were explored by integrating molecular docking analysis with surface plasmon resonance (SPR) assay. The results showed that GA significantly enhanced the anti-tumor effects, cytokine production as well as the expansion of anti-CD19 CAR-T cells, which may be mainly through the activation of IL4/JAK3-STAT3 signaling pathway. Furthermore, GA may directly target and activate STAT3, which may, at least in part, contribute to STAT3 activation. Overall, the findings reported here suggested that the combination of anti-CD19 CAR-T immunotherapy with GA would be a promising approach to increase the anti-lymphoma efficacy.

Development of a compact linear accelerator to generate ultrahigh dose rate high-energy X-rays for FLASH radiotherapy applications.

PURPOSE: In recent years, the FLASH effect, in which ultrahigh dose rate (UHDR) radiotherapy (RT) can significantly reduce toxicity to normal tissue while maintaining antitumor efficacy, has been verified in many studies and even applied in human clinical cases. This work evaluates whether a room-temperature radio-frequency (RF) linear accelerator (linac) system can produce UHDR high-energy X-rays exceeding a dose rate of 40 Gy/s at a clinical source-surface distance (SSD), exploring the possibility of a compact and economical clinical FLASH RT machine suitable for most hospital treatmentrooms. METHODS: A 1.65 m long S-band backward-traveling-wave (BTW) electron linac was developed to generate high-current electron beams, supplied by a commercial klystron-based power source. A tungsten-copper electron-to-photon conversion target for UHDR X-rays was designed and optimized with Monte Carlo (MC) simulations using Geant4 and thermal finite element analysis (FEA) simulations using ANSYS. EBT3 and EBT-XD radiochromic films, which were calibrated with a clinical machine Varian VitalBeam, were used for absolute dose measurements. A PTW ionization chamber detector was used to measure the relative total dose and a plane-parallel ionization chamber detector was used to measure the relative normalized dose of each pulse. RESULTS: The BTW linac generated 300-mA-pulse-current 11 MeV electron beams with 29 kW mean beam power, and the conversion target could sustain this high beam power within a maximum irradiation duration of 0.75 s. The mean energy of the produced X-rays was 1.66 MeV in the MC simulation. The measured flat-filter-free (FFF) maximum mean dose rate of the room-temperature linac exceeded 80 Gy/s at an SSD of 50 cm and 45 Gy/s at an SSD of 67.9 cm, both at a 2.1 cm depth of the water phantom. The FFF radiation fields at 50 cm and 67.9 cm SSD at a 2.1 cm depth of the water phantom showed Gaussian-like distributions with 14.3 and 20 cm full-width at half-maximum (FWHM) values, respectively. CONCLUSION: This work demonstrated the feasibility of UHDR X-rays produced by a room-temperature RF linac, and explored the further optimization of system stability. It shows that a simple and compact UHDR X-ray solution can be facilitated for both FLASH-RT scientific research and clinical applications.

Effectiveness and safety of moxibustion for vascular dementia: A systematic review and meta-analysis.

BACKGROUND: Vascular dementia (VD) is the only type of dementia that can be prevented and treated. Compared to conventional treatment methods, moxibustion therapy is more effective for VD. This study evaluated the effectiveness and safety of moxibustion in the treatment of VD through a meta-analysis, to provide a complete overview to the advantages of traditional Chinese medicine and provide guidance for clinical application. METHODS: Clinical trials on the therapeutic effects of moxibustion or moxibustion combined with acupuncture on VD were retrieved from the VIP information database, Wanfang, CNKI, PubMed, EMBase, and other resources. The included studies were conducted from January 2000 to October 2020. Among the retrieved studies, the content met the standards upon being collated and extracted, and RevMan5.3 was used for meta-analysis. RESULTS: Thirteen randomized controlled trials (RCTs) were included with 997 patients. The RevMan bias risk assessment revealed that the quality of the studies was generally low. The meta-analysis showed that compared to conventional treatments, moxibution therapy in terms of effective rate, posttreatment Hasegawa Dementia Scale, Mini-Mental State Examination (MMSE), Activity of Daily Living Scale (ADL), Somatostatin (SS), Arginine Vasopressin (AVP), and Syndrome Differentiation Scale of VD were more favorable, and the difference in efficacy was statistically significant. Furthermore, no adverse events were observed in either group. Sensitivity analysis showed strong homogeneity and stable results, whereas funnel plot analysis revealed no significant publication bias. CONCLUSIONS: Moxibustion is effective and safe in the treatment of VD, but more high-quality evidence from further studies is required to support this.

Diffraction based method to reconstruct the spectrum of the Thomson scattering x-ray source.

As Thomson scattering x-ray sources based on the collision of intense laser and relativistic electrons have drawn much attention in various scientific fields, there is an increasing demand for the effective methods to reconstruct the spectrum information of the ultra-short and high-intensity x-ray pulses. In this paper, a precise spectrum measurement method for the Thomson scattering x-ray sources was proposed with the diffraction of a Highly Oriented Pyrolytic Graphite (HOPG) crystal and was demonstrated at the Tsinghua Thomson scattering X-ray source. The x-ray pulse is diffracted by a 15 mm (L) ×15 mm (H)× 1 mm (D) HOPG crystal with 1° mosaic spread. By analyzing the diffraction pattern, both x-ray peak energies and energy spectral bandwidths at different polar angles can be reconstructed, which agree well with the theoretical value and simulation. The higher integral reflectivity of the HOPG crystal makes this method possible for single-shot measurement.

Note: Single-shot continuously time-resolved MeV ultrafast electron diffraction.

We have demonstrated single-shot continuously time-resolved MeV ultrafast electron diffraction using a static single crystal gold sample. An MeV high density electron pulse was used to probe the sample and then streaked by an rf deflecting cavity. The single-shot, high quality, streaked diffraction pattern allowed structural information within several picoseconds to be continuously temporally resolved with an approximately 200 fs resolution. The temporal resolution can be straightforwardly improved to 100 fs by increasing the streaking strength. We foresee that this system would become a powerful tool for ultrafast structural dynamics studies.

Experimental demonstration of high quality MeV ultrafast electron diffraction.

The simulation optimization and an experimental demonstration of improved performances of mega-electron-volt ultrafast electron diffraction (MeV UED) are reported in this paper. Using ultrashort high quality electron pulses from an S-band photocathode rf gun and a polycrystalline aluminum foil as the sample, we experimentally demonstrated an improved spatial resolution of MeV UED, in which the Debye-Scherrer rings of the (111) and (200) planes were clearly resolved. This result showed that MeV UED is capable to achieve an atomic level spatial resolution and a approximately 100 fs temporal resolution simultaneously, and will be a unique tool for ultrafast structural dynamics studies.