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.

A drug-loaded composite coating to improve osteogenic and antibacterial properties of Zn-1Mg porous scaffolds as biodegradable bone implants.

Zinc (Zn) alloy porous scaffolds produced by additive manufacturing own customizable structures and biodegradable functions, having a great application potential for repairing bone defect. In this work, a hydroxyapatite (HA)/polydopamine (PDA) composite coating was constructed on the surface of Zn-1Mg porous scaffolds fabricated by laser powder bed fusion, and was loaded with a bioactive factor BMP2 and an antibacterial drug vancomycin. The microstructure, degradation behavior, biocompatibility, antibacterial performance and osteogenic activities were systematically investigated. Compared with as-built Zn-1Mg scaffolds, the rapid increase of Zn2+, which resulted to the deteriorated cell viability and osteogenic differentiation, was inhibited due to the physical barrier of the composite coating. In vitro cellular and bacterial assay indicated that the loaded BMP2 and vancomycin considerably enhanced the cytocompatibility and antibacterial performance. Significantly improved osteogenic and antibacterial functions were also observed according to in vivo implantation in the lateral femoral condyle of rats. The design, influence and mechanism of the composite coating were discussed accordingly. It was concluded that the additively manufactured Zn-1Mg porous scaffolds together with the composite coating could modulate biodegradable performance and contribute to effective promotion of bone recovery and antibacterial function.

Computerized dynamic occlusal analysis and its correlation with static characters in post-orthodontic patients using the T-Scan system and the ABO objective grading system.

OBJECTIVES: This study was conducted to detect the overall performance of both static and dynamic occlusion in post-orthodontic patients using quantified methods, and to ascertain the correlation between the two states of occlusion. MATERIALS AND METHODS: A total of 112 consecutive patients evaluated by ABO-OGS were included in this study. Based on the pre-treatment Angle's classification of the malocclusion, samples were divided into four groups. After removing orthodontic appliances, each patients underwent the American Board of Orthodontic objective grading system (ABO-OGS) and T-Scan evaluations. All the scores were compared within these groups. Statistical evaluation included reliability tests, multivariate ANOVA, and correlation analyses (p < 0.05 was considered significant). RESULTS: The mean ABO-OGS score was satisfactory and did not differ by Angle classifications. The indices making substantial contributions to ABO-OGS were occlusal contacts, occlusal relationships, overjet, and alignment. Disocclusion time in post-orthodontic patients was longer than normal. Occlusion time, disocclusion time, and force distribution during dynamic motions were considerably influenced by static ABO-OGS measurements, especially occlusal contacts, buccolingual inclination, and alignment. CONCLUSION: Post-orthodontic cases that passed the static evaluation of clinicians and ABO-OGS may nevertheless be left with dental casts interference in dynamic motions. Both static and dynamic occlusion should be extensively evaluated before ending orthodontic treatment. Further research is needed on dynamic occlusal guidelines and standards.

Effect of local application of bone morphogenetic protein -2 on experimental tooth movement and biological remodeling in rats.

Background: This study attempts to detect the potential effects of local bone morphogenetic protein -2 (BMP-2) on orthodontic tooth movement and periodontal tissue remodeling. Methods: Forty adult SD rats were randomly divided into four groups: blank control group, unilateral injection of BMP-2 on the pressure side or tension side of orthodontic teeth and bilateral injection of BMP-2. Their maxillary first molar was moved by a 30 g constant force closed coil spring. 60 µL of BMP-2 with a concentration of 0.5 µg/mL was injected into each part at a time. In addition, three rats were selected as healthy control rats without any intervention. Fluorescent labeled BMP-2 was used to observe the distribution of exogenous BMP-2 in tissues. Micro-CT was used to measure the microscopic parameters of tooth displacement, trabecular bone and root absorption volume. Three different histological methods were used to observe the changes of tissue remodeling, and then the number of osteoclasts and the content of collagen fibers were calculated. Results: Compared with the blank control group, BMP-2 injection reduced the movement distance and increased the collagen fiber content and bone mass (p < 0.01). There was no significant difference in tooth movement distance, BV/TV ratio and BMD between injection sites in unilateral injection group (p > 0.05). In the case of bilateral injection of BMP-2, the osteogenesis is enhanced. Unilateral injection of BMP-2 did not promote root resorption, but double injection showed root resorption (p < 0.01). Conclusion: Our study does show that the osteogenesis of BMP-2 is dose-dependent rather than site-dependent when a certain amount of BMP-2 is applied around orthodontic teeth. Local application of BMP-2 around orthodontic teeth in an appropriate way can enhance bone mass and tooth anchorage without increasing the risk of root absorption volume. However, high levels of BMP-2 may cause aggressive root resorption. These findings are of great significance, that is, BMP-2 is an effective target for regulating orthodontic tooth movement.

Single-pulse characterization of the focal spot size of X-ray free-electron lasers using coherent diffraction imaging.

The characterization of X-ray focal spots is of great significance for the diagnosis and performance optimization of focusing systems. X-ray free-electron lasers (XFELs) are the latest generation of X-ray sources with ultrahigh brilliance, ultrashort pulse duration and nearly full transverse coherence. Because each XFEL pulse is unique and has an ultrahigh peak intensity, it is difficult to characterize its focal spot size individually with full power. Herein, a method for characterizing the spot size at the focus position is proposed based on coherent diffraction imaging. A numerical simulation was conducted to verify the feasibility of the proposed method. The focal spot size of the Coherent Scattering and Imaging endstation at the Shanghai Soft X-ray Free Electron Laser Facility was characterized using the method. The full width at half-maxima of the focal spot intensity and spot size in the horizontal and vertical directions were calculated to be 2.10 ± 0.24 µm and 2.00 ± 0.20 µm, respectively. An ablation imprint on the silicon frame was used to validate the results of the proposed method.

Thermal effects of beam profiles on X-ray photon correlation spectroscopy at megahertz X-ray free-electron lasers.

X-ray free-electron lasers (XFELs) with megahertz repetition rates enable X-ray photon correlation spectroscopy (XPCS) studies of fast dynamics on microsecond and sub-microsecond time scales. Beam-induced sample heating is one of the central concerns in these studies, as the interval time is often insufficient for heat dissipation. Despite the great efforts devoted to this issue, few have evaluated the thermal effects of X-ray beam profiles. This work compares the effective dynamics of three common beam profiles using numerical methods. Results show that under the same fluence, the effective temperatures increase with the nonuniformity of the beam, such that the Gaussian beam profile yields a higher effective temperature than the donut-like and uniform profiles. Moreover, decreasing the beam sizes is found to reduce beam-induced thermal effects, in particular the effects of beam profiles.

Three-Dimensional Quantitative Coherent Diffraction Imaging of Staphylococcus aureus Treated with Peptide-Mineralized Au-Cluster Probes.

Characterizing interactions between microbial cells and their specific inhibitory drugs is essential for developing effective drugs and understanding the therapeutic mechanism. Functional metal nanoclusters can be effective inhibitory agents against microorganisms according to various characterization methods, but quantitative three-dimensional (3D) spatial structural analysis of intact cells is lacking. Herein, using coherent X-ray diffraction imaging, we performed in situ 3D visualization of unstained Staphylococcus aureus cells treated with peptide-mineralized Au-cluster probes at a resolution of ∼47 nm. Subsequent 3D mass-density mapping and quantitative structural analyses of S. aureus in different degrees of destruction showed that the bacterial cell wall was damaged and cytoplasmic constituents were released from cells, confirming the significant antibacterial effects of the Au-cluster probe. This study provides a promising nondestructive approach for quantitative imaging and paves the way for further research into microbe-inhibitor drug interactions.

Quantitative, in situ visualization of intracellular insulin vesicles in pancreatic beta cells.

Characterizing relationships between Zn2+, insulin, and insulin vesicles is of vital importance to the study of pancreatic beta cells. However, the precise content of Zn2+ and the specific location of insulin inside insulin vesicles are not clear, which hinders a thorough understanding of the insulin secretion process and diseases caused by blood sugar dysregulation. Here, we demonstrated the colocalization of Zn2+ and insulin in both single extracellular insulin vesicles and pancreatic beta cells by using an X-ray scanning coherent diffraction imaging (ptychography) technique. We also analyzed the elemental Zn2+ and Ca2+ contents of insulin vesicles using electron microscopy and energy dispersive spectroscopy (EDS) mapping. We found that the presence of Zn2+ is an important characteristic that can be used to distinguish insulin vesicles from other types of vesicles in pancreatic beta cells and that the content of Zn2+ is proportional to the size of insulin vesicles. By using dual-energy contrast X-ray microscopy and scanning transmission X-ray microscopy (STXM) image stacks, we observed that insulin accumulates in the off-center position of extracellular insulin vesicles. Furthermore, the spatial distribution of insulin vesicles and their colocalization with other organelles inside pancreatic beta cells were demonstrated using three-dimensional (3D) imaging by combining X-ray ptychography and an equally sloped tomography (EST) algorithm. This study describes a powerful method to univocally describe the location and quantitative analysis of intracellular insulin, which will be of great significance to the study of diabetes and other blood sugar diseases.

Quantitative analysis of the effect of radiation on mitochondria structure using coherent diffraction imaging with a clustering algorithm.

Radiation damage and a low signal-to-noise ratio are the primary factors that limit spatial resolution in coherent diffraction imaging (CDI) of biomaterials using X-ray sources. Introduced here is a clustering algorithm named ConvRe based on deep learning, and it is applied to obtain accurate and consistent image reconstruction from noisy diffraction patterns of weakly scattering biomaterials. To investigate the impact of X-ray radiation on soft biomaterials, CDI experiments were performed on mitochondria from human embryonic kidney cells using synchrotron radiation. Benefiting from the new algorithm, structural changes in the mitochondria induced by X-ray radiation damage were quantitatively characterized and analysed at the nanoscale with different radiation doses. This work also provides a promising approach for improving the imaging quality of biomaterials with XFEL-based plane-wave CDI.

A comparison of Remdesivir versus gold cluster in COVID-19 animal model: A better therapeutic outcome of gold cluster.

While gold compound have been approved for Rheumatoid arthritis treatment as it well suppresses inflammatory cytokines of patients, no such treatment is currently available for COVID-19 treatment in vivo . We firstly disclose gold cluster yields better therapeutic outcome than Remdesivir in COVID-19 hamster treatments as it is armed with direct inhibition viral replication and intrinsic suppression inflammatory cytokines expression. Crystal data reveals that Au (I), released from gold cluster (GA), covalently binds thiolate of Cys145 of SARS-CoV-2 Mpro. GA directly decreases SARS-CoV-2 viral replication and intrinsically down-regulates NFκB pathway therefore significantly inhibiting expression of inflammatory cytokines in cells. The inflammatory cytokines in GA-treated COVID-19 transgenic mice are found to be significantly lower than that of control mice. When COVID-19 golden hamsters are treated by GA, the lung inflammatory cytokines levels are significantly lower than that of Remdesivir. The pathological results show that GA treatment significantly reduce lung inflammatory injuries when compared to that of Remdesivir-treated COVID-19 hamsters.

Comparison of Biological Characteristics of Different Paranasal Sinus Mucosa in Goats.

BACKGROUND/PURPOSE: Prosthetic implants are the primary treatment for patients with edentulism. This study aims to explore and compare the biological characteristics of mucosal thickness and tensile strength of the paranasal sinuses (maxillary and frontal sinuses) in goats, thereby providing a theoretical basis and guidance for mucosa-related problems involved in maxillary sinus lifting. MATERIALS AND METHODS: The paranasal sinus mucosa (maxillary sinus crest, maxillary sinus floor and frontal sinus mucosa) was obtained from the goats for use in maxillary sinus lifting. The mucosa was made into tissue section specimens and evaluated by a computer with built-in screenshot software and an optical microscope with a graduated eyepiece. A total of 3 readings were randomly selected and recorded. The mucosa was clamped with a laboratory-made clamp device. After connecting the push-pull meter, the mucosa exposed by the inner ring of the clamp device was pressed vertically and uniformly until it ruptured. The strength value was read and recorded. The left and right ends of the mucosa were connected with the clamp device; horizontal tension was applied evenly to the mucosa until the mucosa ruptured. The strength value was read and recorded. The normality test, analysis of variance, LSD pairwise comparison and linear regression were performed for each group of data. RESULTS: The thicknesses of the maxillary sinus crest mucosa, floor mucosa and frontal sinus mucosa in goats were 410.03 ± 65.97 um, 461.33 ± 91.37 um and 216.90 ± 46.47 um, respectively. There were significant differences between the maxillary sinus crest and frontal sinus and the maxillary sinus floor and frontal sinus (P < .05). The range of tensile strength of the maxillary sinus crest mucosa, floor mucosa and frontal sinus mucosa in goats was 0.48 ± 0.10 kg, 0.54 ± 0.11kg and 0.20 ± 0.05kg, respectively. There were significant differences between the maxillary sinus crest and frontal sinus and the maxillary sinus floor and frontal sinus (P < .05). Tensile strength was positively correlated with the thickness of the mucosa of the maxillary and frontal sinuses (P < .05). CONCLUSION: The mucosal thickness and tensile strength of the maxillary sinus crest and floor were greater than those of the frontal sinus mucosa. There was a positive correlation between the tensile strength and the thickness of the mucosa.

Inducing thermodynamically blocked atomic ordering via strongly driven nonequilibrium kinetics.

Ultrafast light-matter interactions enable inducing exotic material phases by promoting access to kinetic processes blocked in equilibrium. Despite potential opportunities, actively using nonequilibrium kinetics for material discovery is limited by the poor understanding on intermediate states of driven systems. Here, using single-pulse time-resolved imaging with x-ray free-electron lasers, we found intermediate states of photoexcited bismuth nanoparticles that showed kinetically reversed surface ordering during ultrafast melting. This entropy-lowering reaction was further investigated by molecular dynamics simulations to reveal that observed kinetics were thermodynamically buried in equilibrium, which emphasized the critical role of electron-mediated ultrafast free-energy modification in inducing exotic material phases. This study demonstrated that ultrafast photoexcitations of electrons provide an efficient strategy to induce hidden material phases by overcoming thermodynamic barriers via nonequilibrium reaction pathways.

VEGF as a potential molecular target in periodontitis: a meta-analysis and microarray data validation.

BACKGROUND: Anti-vascular endothelial growth factor (VEGF) has been used as a therapeutic drug for the treatment of some human diseases. However, no systematic evidence is performed for assessing the role of VEGF in periodontitis. We carried out a comprehensive analysis to explore the role of VEGF in patients with periodontitis. METHODS: Multiple databases were searched for eligible studies. The pooled standardized mean difference (SMD) and odds ratio (OR) with the corresponding 95% confidence interval (CI) were applied to evaluate the effect sizes. Clinical data validation from microarray analysis was used. Pathway and process enrichment analysis were also investigated. RESULTS: Finally, 16 studies were included in this analysis. Overall, there was a significantly higher level of VEGF expression in periodontitis than in healthy control groups (OR = 16.64, 95% CI = 6.01-46.06, P < 0.001; SMD = 2.25, 95% CI = 1.25-3.24, P < 0.001). Subgroup analysis of ethnicity showed that VEGF expression was still correlated with periodontitis in the Asian and European populations. No correlation was observed between VEGF expression and age, gender, and pathological type. A large clinical sample data (427 periodontitis patients and 136 healthy controls) further validated that VEGF expression was higher in periodontitis than in healthy control groups (P = 0.023). VEGF was involved in many functions such as blood vessel development, response to growth factor, cell proliferation, and cell adhesion. CONCLUSIONS: High levels of VEGF were credible implications for the development of periodontitis. Anti-VEGF therapy may be valuable for the treatment of periodontitis in clinical management.

Nanoscale Detection of Subcellular Nanoparticles by X-Ray Diffraction Imaging for Precise Quantitative Analysis of Whole Cancer Cells.

Nanoparticles show great potential for drug delivery systems in cancer treatment and diagnosis, which mainly rely on the interaction between nanoparticles and living cells. However, there is still a lack of accurate and large field-of-view imaging techniques to reveal the aggregation and distribution behavior of nanoparticles in whole cancer cells without being destroyed. Here, we demonstrated quantitative imaging of unstained and intact mouse breast cancer cells (4T1) containing 50 nm gold nanoparticles (Au@citrate NPs) using an X-ray scanning coherent diffraction imaging (ptychography) technique in a large field-of-view. A two-dimensional spatial resolution of 17 nm was achieved on the 4T1 cell. We combine X-ray ptychography and equally sloped tomography (EST) to perform three-dimensional structural mapping, distribution, and aggregation behavior of Au@citrate NPs in cancer cells. By taking full advantage of the large field-of-view, high-resolution, and quantitative imaging technique, the single intracellular Au@citrate NPs are observed and the amount of Au@citrate NPs in aggregations can be accurately quantified. In addition, the morphological changes of lysosomes containing Au@citrate NPs can be observed in the high-contrast mass density images. This study provides an approach for exploring quantitative analysis and physiological delivery of nanomaterials in intact cancer cells at nanoscale resolution, which may greatly benefit the interdisciplinary research of material science, nanomedicine, and nanotoxicology.

Preventing nickel-titanium rotary instrument from breakage by continuous irrigation with different fluids during root canal preparation.

ABSTRACT: To study the effect of continuous irrigation of rotating nickel-titanium instrument with several common clinical fluids on the diameter, breaking length and breaking position of nickel-titanium instrument, so as to provide some reference and theoretical basis for clinical operation and instrument improvement.A standardized curved root canal model was established, and ProTaper Universal (PTU) F1 instrument was selected for root canal preparation. The nickel-titanium F1 instrument was flushed with distilled water, 0.9% NaCl, 0.2% chlorhexidine, 1% sodium hypochlorite and 5% sodium hypochlorite, and the diameter, length and position of the instrument before and after breakage were recorded.Only 5% sodium hypochlorite influenced the diameter of 6 mm marker points under different irrigation conditions (P < .05). There was no statistical difference in the length of broken instruments among all the groups, and torsional deformation mainly occurred at the end of broken instruments. The broken positions of instruments in all the groups were located at the bending segment of the root canal. The breaking frequency of the 5% sodium hypochlorite group was the highest in the area 3-5.5 mm away from apical foramen, while the other 4 groups had the highest breaking frequency in the area 0 to 1.5 mm away from apical foramen.External irrigation with different fluids did not influence the breaking length of instruments. The closer to the apical foramen was, the higher the breaking frequency of instruments was. However, only 5% sodium hypochlorite can affect the diameter of rotary nickel-titanium instruments, and may lead to early breakage of the instrument, indicating that the use of disinfectants, except 5% sodium hypochlorite, cannot reduce breakage resistance of nickel-titanium instrument compared with distilled water flushing. Furthermore, 5% hypochlorite could not be recommended for irrigation in clinical practice.

Characterizing the intrinsic properties of individual XFEL pulses via single-particle diffraction.

With each single X-ray pulse having its own characteristics, understanding the individual property of each X-ray free-electron laser (XFEL) pulse is essential for its applications in probing and manipulating specimens as well as in diagnosing the lasing performance. Intensive research using XFEL radiation over the last several years has introduced techniques to characterize the femtosecond XFEL pulses, but a simple characterization scheme, while not requiring ad hoc assumptions, to address multiple aspects of XFEL radiation via a single data collection process is scant. Here, it is shown that single-particle diffraction patterns collected using single XFEL pulses can provide information about the incident photon flux and coherence property simultaneously, and the X-ray beam profile is inferred. The proposed scheme is highly adaptable to most experimental configurations, and will become an essential approach to understanding single X-ray pulses.

[Comparison of stripping of steep sheep maxillary sinus mucosal with new-type memory elastic silk sleeve stripper and umbrella stripper].

OBJECTIVE: This work aims to investigate the effect of stripping of steep sheep maxillary sinus by using 0.012 or 0.014 model new-type memory elastic silk sleeve stripper and umbrella stripper. METHODS: Goats with sinus floor gradients of 60° to 90° were selected by computed tomography of sheep head. A total of 72 animal models were established and randomized into three groups (n=24): group A (0.012 model), B (0.014 model) and C (umbrella stripper). Alveolar and maxillary sinus mucosa were stripped after crowning, and stripping length was measured when the stripping limit was reached or mucosal perforation occurred. RESULTS: The average stripping length of mucosa in group A was 11.3 mm±4.6 mm, and three cases experienced perforation of sinus floor mucosa. The average stripping length of mucosa in group B was 17.5 mm±5.0 mm, and one case experienced perforation of sinus floor mucosa. The average stripping length of mucosa in group C was 4.2 mm±1.3 mm, and four cases experienced perforation of sinus floor mucosa. The difference among the three groups was statistically significant (P<0.01) according to variance analysis. Moreover, the comparison between any two means was also statistically significant according to Dunnett's T3 test (P<0.05). CONCLUSIONS: The new-type memory elastic silk sleeve stripper effectively stripped steep maxillary sinus mucosa. The 0.014 model exhibited superior peeling effect and was relatively safe.

Enhancement of phase retrieval capability in ptychography by using strongly scattering property of the probe-generating device.

In common ptychographic coherent diffractive imaging (PCDI) systems, the probe-generating devices typically exhibit strong scattering, which is not fully used. Here, we report the reasonableness of using the diffraction pattern of the probe-generating device as the frequency-domain information of the scanning probe located in the sample plane, and we propose a method introducing this frequency-domain information into an iterative process to improve the imaging quality of PCDI. The new method was demonstrated using both a visible laser source and a synchrotron radiation X-ray source; the proposed method significantly improved the imaging quality in both demonstrations.

Necessary Experimental Conditions for Single-Shot Diffraction Imaging of DNA-Based Structures with X-ray Free-Electron Lasers.

It has been proposed that the radiation damage to biological particles and soft condensed matter can be overcome by ultrafast and ultraintense X-ray free-electron lasers (FELs) with short pulse durations. The successful demonstration of the "diffraction-before-destruction" concept has made single-shot diffraction imaging a promising tool to achieve high resolutions under the native states of samples. However, the resolution is still limited because of the low signal-to-noise ratio, especially for biological specimens such as cells, viruses, and macromolecular particles. Here, we present a demonstration single-shot diffraction imaging experiment of DNA-based structures at SPring-8 Angstrom Compact Free Electron Laser (SACLA), Japan. Through quantitative analysis of the reconstructed images, the scattering abilities of gold and DNA were demonstrated. Suggestions for extracting valid DNA signals from noisy diffraction patterns were also explained and outlined. To sketch out the necessary experimental conditions for the 3D imaging of DNA origami or DNA macromolecular particles, we carried out numerical simulations with practical detector noise and experimental geometry using the Linac Coherent Light Source (LCLS) at the SLAC National Accelerator Laboratory, USA. The simulated results demonstrate that it is possible to capture images of DNA-based structures at high resolutions with the technique development of current and next-generation X-ray FEL facilities.