Design and first-round commissioning result of the SASE beamline at the Shanghai Soft X-ray FEL facility.

The Shanghai Soft X-ray Free-Electron Laser (SXFEL) is the first X-ray free-electron laser facility in China. The SASE beamline, which consists of a pink-beam branch and a mono-beam branch, is one of the two beamlines in the Phase-I construction. The pink-beam branch opened for users in 2023 after successful first-round beamline commissioning. In this paper, the design of the beamline is presented and the performance of the pink-beam branch is reported. The measured energy-resolving power of the online spectrometer is over 6000 @ 400 eV. The focusing spot size of the pink beam is less than 3 µm in both the horizontal and vertical at the endstation.

Fabrication of large-area photonic crystal-modified X-ray scintillator imager for optical coding imaging.

The limited pattern area of periodic nanostructures limits the development of practical devices. This study introduces an X-ray interference lithography (XIL) stitching technique to fabricate a large-area (1.5 cm × 1.5 cm) two-dimensional photonic crystal (PhC) on the YAG: Ce scintillator, which functions as an encoder in a high numerical aperture optical encoding imaging system to effectively capture high-frequency information. An X-ray imaging experiment revealed a substantial 7.64 dB improvement in the signal-to-noise ratio (SNR) across a large field of view (2.6 mm × 2.6 mm) and achieved comparable or superior image quality with half the exposure dose. These findings have significant implications for advancing practical applications of X-ray imaging.

Analysis of partially coherent light propagation through the soft X-ray interference lithography beamline at SSRF.

The mutual optical intensity (MOI) model is extended to the simulation of the interference pattern produced by extreme ultraviolet lithography with partially coherent light. The partially coherent X-ray propagation through the BL08U1B beamline at Shanghai Synchrotron Radiation Facility is analysed using the MOI model and SRW (Synchrotron Radiation Workshop) method. The fringe intensity at the exposure area is not uniform but has similar envelope lines to Fresnel diffraction, which is explained by the diffraction from the finite grating modelled as a single aperture. By balancing the slit size and photon stop size, the fringe visibility, photon flux and intensity slope can be optimized. Further analysis shows that the effect of pink light on the aerial images is negligible, whereas the third-harmonic light should be considered to obtain a balance between high fringe visibility and high flux. Two grating interference exposure experiments were performed in the BL08U1B beamline. The aerial image depth showed that the polymethyl methacrylate photoresist depth was determined by the X-ray coherence properties.

Hybrid application of laser-focused atomic deposition and extreme ultraviolet interference lithography methods for manufacturing of self-traceable nanogratings.

A novel hybrid method that combines the laser-focused atomic deposition (LFAD) and extreme ultraviolet (EUV) interference lithography has been introduced. The Cr grating manufactured by LFAD has advantages of excellent uniformity, low line edge roughness and its pitch value determined directly by nature constants (i.e. self-traceable). To further enhance the density of the Cr grating, the EUV interference lithography with 13.4 nm wavelength was employed, which replicated the master Cr grating onto a Si wafer with its pitch reduced to half. In order to verify the performance of the gratings manufactured by this novel method, both mask grating (Cr grating) and replicated grating (silicon grating) were calibrated by the metrological large range scanning probe microscope (Met.LR-SPM) at Physikalisch-Technische Bundesanstalt (PTB). The calibrated results show that both gratings have excellent short-term and long-term uniformity: (i) the calibrated position deviation (i.e. nonlinearity) of the grating is below ±1 nm; (ii) the deviation of mean pitch values of 6 randomly selected measurement locations is below 0.003 nm. In addition, the mean pitch value of the Cr grating is calibrated as 212.781 ± 0.008 nm (k = 2). It well agrees with its theoretical value of 212.7787 ± 0.0049 nm, confirming the self-traceability of the manufactured grating by the LFAD. The mean pitch value of the Si grating is calibrated as 106.460 ± 0.012 nm (k = 2). It corresponds to the shrinking factor of 0.500 33 of the applied EUV interference lithographic technique. This factor is very close to its theoretical value of 0.5. The uniform, self-traceable gratings fabricated using this novel approach can be well applied as reference materials in calibrating, e.g. the magnification and uniformity of almost all kinds of high resolution microscopes for nanotechnology.

A variable fixed-focus constant optimization method for a variable-included-angle varied-line-spacing plane-grating monochromator.

Variable-included-angle varied-line-spacing plane-grating monochromators (VIA-VPGM) have been applied to many beamlines because of the self-focusing and aberration-correction function of the varied-line-spacing grating. Unfortunately, to optimize the variable-line-spacing coefficient of the grating, the fixed-focus constant (Cff) has to be fixed first in the VIA-VPGM. In this way, some of the advantages of these monochromators are lost, such as the flexibility of choosing a different energy-resolving power by varying the Cff. In this work, a variable Cff optimization method is introduced for a VIA-VPGM. By adopting this method, the Cff could be arbitrarily selected in the VIA-VPGM.

Parallel direct writing achromatic talbot lithography: a method for large-area arbitrary sub-micron periodic nano-arrays fabrication.

Metasurfaces with complex periodic nanoarrays have attracted a large amount of attention over the past decades due to their pronounced plasmonic and photonic properties. Though various metasurface properties have been theoretically and experimentally investigated, the realization of practical metasurface applications remains a big challenge due to very limited large-area complex nanostructure fabrication. In this paper, we demonstrate a parallel direct writing achromatic Talbot lithography (DW-ATL) technique for large-area arbitrary sub-micron periodic nano-arrays fabrication. By using a laser interferometer, the sparse hole/dot arrays obtained by ATL could be stitched precisely between discrete multiple exposures. Complex sub-micron periodic nanoarrays, such as elliptical discs, rods, L-shaped and Y-shaped periodic nanoarrays, with a sub-hundred nm resolution were fabricated over an area of ∼mm2.

Thickness-dependent structural characteristics for a sputtering-deposited chromium monolayer and Cr/C and Cr/Sc multilayers.

The interior structure, morphology and ligand surrounding of a sputtering-deposited chromium monolayer and Cr/C and Cr/Sc multilayers are determined by various hard X-ray techniques in order to reveal the growth characteristics of Cr-based thin films. A Cr monolayer presents a three-stage growth mode with sudden changes occurring at a layer thickness of ∼2 nm and beyond 6 nm. Cr-based multilayers are proven to have denser structures due to interfacial diffusion and layer growth mode. Cr/C and Cr/Sc multilayers have different interfacial widths resulting from asymmetry, degree of crystallinity and thermal stability. Cr/Sc multilayers present similar ligand surroundings to Cr foil, whereas Cr/C multilayers are similar to Cr monolayers. The aim of this study is to help understand the structural evolution regulation versus layer thickness and to improve the deposition technology of Cr-based thin films, in particular for obtaining stable Cr-based multilayers with ultra-short periods.

The wave optical whole process design of the soft X-ray interference lithography beamline at SSRF.

A new spatially coherent beamline has been designed and constructed at the Shanghai Synchrotron Radiation Facility. Here, the design of the beamline is introduced and the spatial coherence is analyzed throughout the whole process by wave optics. The simulation results show good spatial coherence at the endstation and have been proven by experiment results.

Guided-mode resonance assisted directional emission of a wavelength-shifting film for application in scintillation detection.

Thin-film luminescent layers as wavelength shifters using in the scintillation detection system suffer with low efficiency due to the total internal reflection and the non-directional emission. In the present work, we design and fabricate a photonic crystal on the surface of LuTaO(4):Eu(3+) thin-film which is a newly developed luminescent material using in radiation detection systems. The entire structure shows guided-mode resonances with only one TE and TM mode. As a result, the emitting light is effectively extracted. Furthermore, due to only two modes existing in the layer, the directionality of emission is strongly controlled. This result enables the structured LuTaO(4):Eu(3+) thin-film to be a potential wavelength shifter with high-efficiency.

Applications of VUV extra-focus mechanism: high-performance dual-mode monochromator from VUV to soft X-ray.

A new monochromator scheme is presented in which an extra-focus constant-included-angle varied-line-spacing cylindrical-grating monochromator (extra-focus CIA-VCGM) is conveniently combined with a variable-included-angle varied-line-spacing plane-grating monochromator (VIA-VPGM). This dual-mode solution delivers high performance in the energy range from vacuum ultraviolet (VUV) to soft X-ray. The resolving power and the efficiency of this dual-mode grating monochromator are analyzed in detail based on realistic parameters. Comparisons with the commonly used variable-included-angle plane-grating monochromator and normal-incidence monochromator (VIA-PGM/NIM) hybrid monochromator are made.

A new extra-focus monochromator designed for high-performance VUV beamlines.

A new monochromator called an extra-focus constant-included-angle varied-line-spacing (VLS) cylindrical-grating monochromator (extra-focus CIA-VCGM) is described. This monochromator is based on the Hettrick-Underwood scheme where the plane VLS grating is replaced by a cylindrical one in order to zero the defocus at three reference photon energies in the vacuum-ultraviolet range. It has a simple mechanical structure and a fixed focus spot with high performance over a wide energy range. Furthermore, its mechanical compatibility with a standard VLS plane-grating monochromator allows convenient extension into the soft-X-ray range.

Numerical analysis of partially coherent radiation at soft x-ray beamline.

A new model for numerical analysis of partially coherent x-ray at synchrotron beamlines is presented. The model is based on statistical optics. Four-dimensional coherence function, Mutual Optical Intensity (MOI), is applied to describe the wavefront of the partially coherent light. The propagation of MOI through optical elements in the beamline is deduced with numerical calculation. The coherence of x-ray through beamlines can be acquired. We applied the model to analyze the coherence in the STXM beamline at SSRF, and got the coherence length of the beam at the endstation. To verify the theoretical results, the diffraction experiment of a single slit was performed and the diffraction pattern was simulated to get the coherence length, (31 ± 3.0) µm × (25 ± 2.1) µm (H × V), which had a good agreement with the theoretical results, (30.7 ± 0.6) µm × (31 ± 5.3) µm (H × V). The model is applicable to analyze the coherence in synchrotron beamlines.

Camrelizumab for the treatment of advanced cervical adenocarcinoma: a case report and literature review.

Cervical adenocarcinoma belongs to an invasive subtype of cervical carcinoma, presenting poorly prognostic status. Chemotherapy treatment for recurrent cervical carcinoma are thought to be limited and supposed to be noncurative. Because of the poor prognosis of patients with recurrent cervical carcinoma, however, the benefits of second-line chemotherapy have not yet reached a consensus. Immunotherapy is a split-new tactic of overwhelming carcinomas that relies on the instinct of the immune system to recognize and directly kill neoplasm cells. Here, we reported a 55-year-old female patient with clinical stage IVB cervical adenocarcinoma. The patient received four cycles of systematic therapy, with the regimen of docetaxel plus carboplatin in combined with bevacizumab anti-vascular therapy. The progressive disease (PD) was assessed by imaging evaluation and PD was confirmed once more after four cycles of chemotherapy of albumin paclitaxel plus cisplatin. The patient exhibited a good response during the twelve-cycle of immunotherapy of Camrelizumab, whereas PD was observed upon termination of her immunotherapy. This case with the treatment of PD-1 inhibitor Camrelizumab exhibits a good curative effect and tolerable adverse reactions. In addition, some clinical markers and biomarkers expression levels can be served as the predictors of the effect of anti-PD-1 immunotherapy.

Optimal Treatments for NSCLC Patients Harboring Primary or Acquired MET Amplification.

Background: In non-small cell lung cancer (NSCLC) patients harboring MET mutations, MET-tyrosine kinase inhibitors (TKIs) have been proven to achieve a good response. However, the relative efficacy of different therapeutics in primary NSCLC patients with MET amplification and the treatment options for patients harboring acquired MET amplification after the failure of epidermal growth factor receptor (EGFR)-TKIs remain unclear. Methods: In total, 33 patients harboring primary MET amplification and 9 patients harboring acquired MET alterations identified by next-generation sequencing were enrolled. A retrospective analysis was conducted to compare the efficacy of different therapeutics. In addition, studies reporting various treatments for patients harboring MET alterations were included in the meta-analysis. Results: In our cohort of patients harboring primary MET amplification, crizotinib displayed better efficacy than immunotherapy and chemotherapy, as demonstrated both in first-line (P = .0378) and second-line treatment regimens (P = .0181). The disease control rates for crizotinib, immunotherapy, and chemotherapy were 81.8%, 72.7%, and 63.6%, respectively. In particular, the median progression-free survival (PFS) time after immunotherapy in patients harboring MET amplification and high programed death ligand 1 (PD-L1) expression (>50%) was only 77.5 days. The meta-analysis revealed that the median PFS times after crizotinib and immunotherapy were 4.57 and 2.94 months, respectively. In patients harboring acquired MET amplification, chemotherapy plus bevacizumab had superior efficacy (310.0 days vs 73.5 days, P = .0360) compared with MET-TKIs ± EGFR-TKIs. Conclusions: Immunotherapy showed a low response in patients harboring MET alterations, even those with concurrent high PD-L1 expression. MET-TKIs might be an optional treatment with worth-expecting efficacy. However, chemotherapy plus bevacizumab could benefit the subpopulation of patients harboring acquired MET amplification after the failure of EGFR-TKIs.

Nrf2 attenuates ferroptosis-mediated IIR-ALI by modulating TERT and SLC7A11.

Acute lung injury (ALI) carries a mortality rate of ~50% and is a hot topic in the world of critical illness research. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical modulator of intracellular oxidative homeostasis and serves as an antioxidant. The Nrf2-related anti-oxidative stress is strongly associated with ferroptosis suppression. Meanwhile, telomerase reverse transcriptase (TERT), the catalytic portion of the telomerase protein, is reported to travel to the mitochondria to alleviate ROS. In our study, we found that TERT was significantly reduced in lung tissue of Nrf2-/- mice in the model of intestinal ischemia/reperfusion-induced acute lung injury (IIR-ALI). In addition, MDA levels showed marked increase, whereas GSH and GPX4 levels fell drastically in ALI models. Moreover, typical-related structural changes were observed in the type II alveolar epithelial cells in the IIR model. We further employed the scanning transmission X-ray microscopy (STXM) to examine Fe levels and distribution within cells. Based on our observations, massive aggregates of Fe were found in the MLE-12 cells upon OGD/R (oxygen and glucose deprivation/reperfusion) induction. Additionally, Nrf2 silencing dramatically reduced TERT and SLC7A11 levels, and further exacerbated cellular injuries. In contrast, TERT-overexpressing cells exhibited marked elevation in SLC7A11 levels and thereby inhibited ferroptosis. Collectively, these data suggest that Nrf2 can negatively regulate ferroptosis via modulation of TERT and SLC7A11 levels. The conclusion from this study brings insight into new candidates that can be targeted in future IIR-ALI therapy.

Association between G-protein coupled receptor 4 expression and microvessel density, clinicopathological characteristics and survival in hepatocellular carcinoma.

G-protein coupled receptor 4 (GPR4) acts as a proton-sensing receptor and plays a role in regulating angiogenesis. Endoglin/CD105 is a marker of cell proliferation in vascular endothelial cells, particularly in tumor vasculature cells. Although there have been several studies investigating angiogenesis in hepatocellular carcinoma (HCC), none have investigated the association between GPR4 and microvessel density (MVD)-CD105 in this type of cancer. In the present study, CD105 and GPR4 were found to be expressed in benign and malignant liver tissues by immunofluorescence staining and laser confocal microscopy. Compared with levels in benign tissues, CD105 and GPR4 were highly expressed in neoplastic tissues. Furthermore, the average fluorescence intensity of GPR4 and MVD-CD105 was positively correlated. GPR4 and CD105 were found to be co-localized in the vascular endothelium in tumor tissues. Furthermore, the expression of GPR4 was higher in the marginal region of tumor tissues compared with the central region. These findings suggest that the expression of GPR4 in tumor microvessels in HCC may be implicated in tumor angiogenesis and development. Furthermore, the association between the expression of GPR4 and the clinicopathological features of patients with HCC further suggests a role for GPR4 in tumor angiogenesis and growth. Overall, these results suggest the potential of GPR4 as a prognostic factor and as an antiangiogenic target in patients with HCC.

Endocrine Therapy for Ductal Carcinoma In Situ (DCIS) of the Breast with Breast Conserving Surgery (BCS) and Radiotherapy (RT): a Meta-Analysis.

The management of ductal carcinoma in situ (DCIS) with endocrine therapy remains controversial. A meta-analysis was conducted to evaluate the role of endocrine therapy for DCIS with breast conserving surgery (BCS) and radiotherapy (RT). A total of 7 articles with randomized controlled trials were included. Five articles compared the effects of BCS and RT followed by tamoxifen (TAM) or not (BCS + RT + TAM vs BCS + RT) and 2 compared the effects of TAM and anastrozole (ANA). TAM obviously reduced the rates of recurrence of ipsilateral breast cancer (IBCR), recurrence of contralateral breast cancer (CBCR), recurrence of ipsilateral invasive breast cancer (IBCR-INV) and recurrence of contralateral DCIS (CBCR-DCIS), and increased the rate of event-free survival (EFS). While ANA reduced the rates of CBCR and recurrence of contralateral invasive breast cancer (CBCR-INV). Patients with ANA had higher incidence of arthralgia, osteoporosis, hypercholesteremia, headache and vaginal dryness, but lower incidence of deep-vein thrombosis, pulmonary embolism, vasomotor or gynaecological, hot flushes, vaginal haemorrhage, vaginal discharge and vaginal candidiasis than TAM. In conclusion, DCIS patients with positive hormone receptors should be recommended to receive endocrine therapy. Selection of TAM or ANA is based on clinical characteristics and underlying disease of patients, as well as the side-effects of drugs.

Dosimetric comparison between IMRT and VMAT in irradiation for peripheral and central lung cancer.

The aim of the present study was to compare intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) in irradiation of lung cancer. Plans of 14 patients were compared. The results demonstrated that in peripheral lung cancer, V5 (%) of the lung in partial-arc (PA)-VMAT was decreased compared with IMRT, single-arc (SA)-, and double partial-arc (2PA)-VMAT. V30 (%) of the lung in IMRT was decreased compared with SA-, PA- and 2PA-VMAT. In the case of planning target volume (PTV) not encompassing the mediastinum in central lung cancer, the conformality index (CI) and heterogeneity index (HI) of SA-VMAT was improved compared with IMRT, PA-, and 2PA-VMAT. The received dose of heart in SA-VMAT was higher compared with IMRT, PA- and 2PA-VMAT. V30 (%) and V5 (%) of the lung in IMRT was higher compared with SA-, PA- and 2PA-VMAT; V10 (%) of the lung in 2PA was decreased compared with IMRT, SA- and PA. In the case of PTV encompassing the mediastinum in central lung cancer, the HI and CI of 2PA was improved compared with IMRT, SA- and PA-VMAT. The received dose of heart in 2PA was higher compared with IMRT, SA- and PA-VMAT. V30 (%) and V5 (%) of the lung in 2PA-VMAT was higher compared with IMRT, SA- and PA-VMAT. V20 (%) of the lung in 2PA was decreased compared with IMRT, SA- and PA-VMAT. In conclusion, it may be necessary to classify the radiotherapy plans of lung cancer into three categories including peripheral lung cancer, PTV not encompassing the mediastinum of central lung cancer, and PTV encompassing the mediastinum of central lung cancer. Each of IMRT, SA-VMAT, PA-VMAT, 2PA-VMAT strategy had individual advantages, and therefore it may be crucial to employ different planning techniques for different disease classifications and OAR requirements.

Directional emission of plastic luminescent films using photonic crystals fabricated by soft-X-ray interference lithography and reactive ion etching.

In this report, a novel method to prepare photonic crystals based on the combination of soft-X-ray interference lithography (XIL) and reactive ion etching (RIE) with a bi-layer photoresist system was developed. XIL can be utilized to prepare periodic structures with high efficiency but the depth of etch is limited due to the strong absorption of photoresist for soft-X-ray. Based on the pattern prepared by XIL, RIE can be utilized to further etch a second layer of photoresist, so that one can obtain a large depth of etch. Controlling the dispersion relation of the prepared photonic crystals, strongly directional emission of plastic luminescent films was demonstrated. A wavelength-integrated enhancement of 2.64-folds enhancement in the range of 420 to 440 nm in the normal direction was obtained. Guided-mode resonance and Fabry-Perot resonance could be the critical factors to control the directional emission. Devices based on directional emission films have a variety of applications in such as detectors, optical communication and display screens.

Development of broadband X-ray interference lithography large area exposure system.

The single-exposure patterned area is about several 10(2) × 10(2) µm(2) which is mainly decided by the mask area in multi-beam X-ray interference lithography (XIL). The exposure area is difficult to stitch to a larger one because the patterned area is surrounded by 0th diffraction exposure areas. To block the 0th diffraction beams precisely and effectively, a new large area exposure technology is developed in the Shanghai Synchrotron Radiation Facility by applying an order-sorting aperture with a new in situ monitoring scheme in the XIL system. The patterned area could be stitched readily up to several square centimeters and even bigger by this technology.