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Small cell lung cancer (SCLC) is characterized by a high relapse rate, drug tolerance, and limited treatment choices. Chimeric antigen receptor (CAR)‐modified NK cells represent a promising immunotherapeutic modality for cancer treatment. However, their potential applications have not been explored in SCLC. Delta‐like ligand 3 (DLL3) has been reported to be overexpressed in SCLC and may be a rational target for CAR NK immunotherapy. In this study, we developed DLL3‐specific NK‐92 cells and explored their potential in the treatment of SCLC. A coculture of DLL3+SCLC cell lines with DLL3‐CAR NK‐92 cells exhibited significant in vitro cytotoxicity and cytokine production. DLL3‐CAR NK‐92 cells induced tumor regression in an H446‐derived pulmonary metastasis tumor model under a good safety threshold. The potent antitumor activities of DLL3‐CAR NK‐92 cells were observed in subcutaneous tumor models of SCLC. Moreover, obvious tumor‐infiltrated DLL3‐CAR NK‐92 cells were detected in DLL3+SCLC xenografts. These findings indicate that DLL3‐CAR NK‐92 cells might be a potential strategy for the treatment of SCLC. DLL3‐CAR NK‐92 cells showed significant anti‐tumor effect on small cell lung cancer both in vitro and in vivo.

•A CDC7 inhibitor XL413 effectively enhanced the chemotherapeutic effect of carboplatin.•Mechanistically, the CDC7 inhibitor XL413 increases the accumulation of chemotherapy-induced DNA damage by inhibiting homologous recombination repair activity and delaying the recovery of DNA double-strand breaks.•XL413 reduced relapses after treatment with carboplatin in vitro and in vivo.

Acute myeloid leukemia (AML) is caused by the abnormal proliferation and differentiation of a clonal population of myeloid progenitors. EBF1 is a key transcriptional factor in regulating hematopoiesis and has been linked to acute lymphoblastic leukemia (ALL). However, the relationship between AML and EBF1mutation has not yet been studied. Recent research has shown that deleting EBF1results in myeloid-biased progenitors and decreased HSC quiescence and repopulation capacity. This suggests that EBF1 is involved in earlier hematopoiesis and has additional functions beyond B-cell committed development.

Nonlinear photothermal microscopy, in which the intensity of the pump heating beam is modulated at f and the photothermal signal is extracted from the probe beam with a lock-in amplifier referred to 2f, is applied to the imaging of mouse melanoma without any staining. The pump and probe pulses, with central wavelengths of 488 and 632 nm, and a pulse duration of ∼100  ps, are filtered from a compact commercial supercontinuum fiber laser source. An auto-balanced detector is applied to accumulate the signal and remove the laser noise of the probe. The spatial resolution of the nonlinear photothermal imaging is enhanced by ∼18% in both theoretical calculations and experiments, compared with a linear photothermal mechanism, and the resolution enhancement is theoretically ∼42% compared with conventional optical microscopy. This imaging technique shows possibilities for the clinical evaluation of melanoma with a high contrast and spatial resolution.

Abstract: In this paper, a learning-based high-speed reconstruction system for ultra-low resolution faces is implemented using a software/hardware co-design paradigm. The hardware component working at 60 MHz contains a field programmable gate array, which is reconfigured to contain parallel processing units, and multiple memories to create parallel data. The hardware component effectively handles generating and sorting computationally intensive similarity metrics. This solves the processing speed problem in learning-based super-resolution reconstruction for ultra-low resolution faces. The system can reconstruct faces using 8×6, 16×12, and 32×24 sized images, with 4×4, 8×8, or 16×16 times magnification. The experimental results verify the effectiveness of our system in terms of both visual effect and low root mean square errors. The processing speed can be improved up to a maximum of 7900 times faster than a pure software implementation using C.

Acute myeloid leukemia(AML) is characterized by an accumulation of myeloid progenitors. This disease can be caused by various germline mutations, including runx1 and asxl1. Recently several reports showed that mutations of ASXL1 and RUNX1 tend to coexist in AML patients. However, the impact on hematopoiesis remained uncertain. Thus far, lack of an animal model was the main limitation to study the function of the double mutations. In this work, we studied the combination role of runx1 and asxl1 by establishing a novel in vivo zebrafish model. First, we identified the characterization of 6646 patients with myeloid maliganacies in the cbioprotal database. Second, we generated a zebrafish model with double mutations by crossing the ENU-induced runx1 mutant and the CRISPR-CAS9 edited asxl1 mutant. Our results showed that truncation was the most frequent mutation type in RUNX1-mutated patients(56.3%) and ASXL1-mutated patients(87.8%). Besides, the median survival time of patients carrying double mutations was shorter than those with single RUNX1 mutation(9.61 months vs. 16.06 months ) or single ASXL1 mutation(9.61 months vs. 14.47 months). In zebrafish models, we found that the pu.1(myeloid precursor marker) positive cells increased while the gata1(proerythrocyte marker) didn't change in double mutants . Furthermore, mpo and lyz (neutrophil marker) positive cells further reduced while mpeg1 and mfap4(monocyte marker) positive cells didn't show significant difference in double mutants.Overall, we demonstrated that ASXL1 mutation cooperating with RUNX1 mutation further impeded the differentiation of the myeloid progenitors into mature neutrophils and it possibly explained the cause for a worse prognosis of patients with double mutations.

No relevant conflicts of interest to declare.

Sub-20-fs deep ultraviolet (DUV) pulses are generated by using nondegenerate, chirped-pulse four-wave mixing of the fundamental and second-harmonic pulses from a commercial Ti:sapphire amplifier in a CaF_2 plate. The energy of the DUV pulses is 3.8 μJ, with a conversion efficiency from total pump energy to DUV of ∼3.8%. The DUV pulse is compressed using a pre-chirp, introduced via a fused silica window in the fundamental beam. The central wavelength of the DUV spectrum can be tuned from 257 to 277 nm by adjusting the cross angle between the two pump beams. The spectrum can reach a width of 16.8 nm, which can support a pulse duration of 8.7 fs.

Diode-pumped laser action of a new crystal Yb^3+:_2Si_2O_7 (LPS) is demonstrated for the first time to our knowledge. An output power of 2.22 W at 1070 nm and a slope efficiency of 34.7% were achieved with a 5 at.-% Yb: LPS sample. The tuning can cover the range form 1034 to 1080 nm.

The brushless doubly-fed induction generator (BDFIG) provides an interesting alternative to the commonly applied conventional doubly-fed induction generator in wind turbines. In this paper, a novel voltage control strategy of stand-alone operation BDFIG for variable speed constant frequency wind energy conversion systems was presented. Based on the model of the generator, the power winding stator voltage and flux for stand-alone operation BDFIG are only determined by the equivalent PW stator magnetizing current which are independent of load, but PW stator terminal output power is only determined by load. An indirect PW stator flux orientated vector control scheme is employed to control the BDFIG by regulating the amplitude and frequency of the control winding stator current appropriately, and this results in constant generator terminal voltage and frequency for variations in both load and wind speed. In addition, simulation results prove the feasibility and validity of the proposed scheme, and excellent steady and dynamic state performance is achieved.

Multilevel current source converter has the benefits of high output capacity, low current switching stress and low harmonic or ripple content. This paper presents a new topology of three-level current-fed DC/DC converter for superconducting magnetic energy storage application. In this topology, a superconducting inductance acting as a constant current source and a shunt inductance acts as current divider ensure current flows through the power switch components equally to generate immediate level of current. A novel kind of pulse width modulation (PWM) switching strategy for the current instantaneous control of the current source converter was proposed. The modulation switching strategy proposed is able to effectively control the DC current output of the converter. Also, due to the both of proposed topology and control method are quite a simple, it can be easily realized in the practice. Simulation results prove the feasibility and validity of the proposed topology and modulation strategy

The frequency converter has been applied in the beam pumping unit, but the field application is still immature, and the energy saving effect is not ideal. This paper briefly analyzes the movement law of the beam pumping unit, and makes a proper simplification of the suspension point load. It derives the work done by the motor in one stroke of the steam head, and combines the oil recovery per unit time of the pumping unit. The operating law of the inverter when the ratio of motor energy consumption to oil production is the smallest. Finally, through simulation analysis, it is verified that the energy consumption of the slow and fast operation mode is lower than that of the constant speed operation mode.

A compact high-power picosecond regenerative amplifier based on continuous wave (CW) diode side-pumped Nd:YAG is demonstrated. Average power of 8.8 W is achieved at a repetition rate of 5 kHz at a wavelength of 1 064 nm with a pulse duration of 28 ps, corresponding to a pulse energy of 1.76 mJ and a peak power of 62.9 MW. The beam quality is close to the diffraction limit with M2x = 1.24, M2y =1.03. To the best of our knowledge, this is the highest pulse energy obtained from a CW diode pumped Nd:YAG picosecond regenerative amplifier.

An efficient high-power diode-pumped femtosecond Yb:KGW laser is repored. Through optimization of energy density by semiconductor saturable absorber mirror, output power achieved 2.4 W with pulse duration of 350 fs and repetition rate of 53 MHz at a pump power of 12.5 W, corresponding to an optical-to-optical efficiency of 19.2%. We believe that it is the highest optical-to-optical efficiency for single-diode-pumped bulk Yb:KGW femtosecond lasers to date.

We reports on a diode-pumped passively mode-locked Yb:SSO laser with a SESAM. Pulses duration as short as ~2 ps with a repetition rate of 53 MHz were generated. The output power achieved ~1.9 W at a pump power of 11.5 W.

Diode-pumped soliton and non-soliton mode-locked Yb:(Gd1-xYx) 2SiO5(x=0.5) lasers have been demonstrated together for the first time to the author's knowledge. For the non-soliton mode locking, output power could achieve ~1.2 W, and pulse width was about 20ps. For the soliton mode-locked operation, the pulse width was 1.4ps at the wavelength of 1056nm and 375fs at the wavelength of 1042nm, with a pair of SF10 prisms as the negative dispersion elements. The repetition rate was 48 MHz. The critical pulse energy in the soliton-mode locked operation against the Q-switched mode locking was much lower than the value in non-soliton mode-locked operation.