Single-exposure multi-wavelength optical diffraction tomography based on space-angle dual multiplexing holography.

We present a space-angle dual multiplexing holographic recording system for realizing single-exposure multi-wavelength optical diffraction tomographic (ODT) imaging. This system is achieved by combining the principle of single-exposure multi-wavelength holographic imaging technique based on angle-division multiplexing with the principle of single-exposure ODT imaging technique based on microlens array multi-angle illuminations and space-division multiplexing. Compared with the existing multi-wavelength ODT imaging methods, it enables the holographic recording of all the diffraction tomography information of a measured specimen at multiple illumination wavelengths in a single camera exposure without any scan mechanism. Using our proposed data processing method, the multi-wavelength three-dimensional (3D) refractive index tomograms of a specimen can be eventually reconstructed from single recorded multiplexing hologram. Experimental results of a static polystyrene bead and a living C. elegans worm demonstrate the feasibility of this system.

Causality Assessment Between Idiopathic Inflammatory Myopathies and Lung Cancer: A Bidirectional 2-Sample Mendelian Randomization.

BACKGROUND: Although observational studies have revealed associations between idiopathic inflammatory myopathies (IIMs) and lung cancer (LC), they have not established a causal relationship between these 2 conditions. METHODS: We used a 2-sample Mendelian randomization approach to examine the bidirectional causal associations between IIMs and LC, using single-nucleotide polymorphisms selected from high-quality genome-wide association studies in the FinnGen database. Sensitivity analyses were conducted to assess potential heterogeneity and pleiotropy impacts on the Mendelian randomization results. RESULTS: Our analysis demonstrated a positive causal effect of genetically increased IIM risk on LC (odds ratio, 1.114; 95% confidence interval, 1.057-1.173; p = 5.63 × 10 -5 ), particularly on the lung squamous cell carcinoma subtype (odds ratio, 1.168, 95% confidence interval, 1.049-1.300, p = 0.00451), but not on lung adenocarcinoma or small cell lung cancer. No causal effect of LC on IIMs was identified. Sensitivity analyses indicated that horizontal pleiotropy was unlikely to influence causality, and leave-one-out analysis confirmed that the observed associations were not driven by a single-nucleotide polymorphism. CONCLUSION: Our findings offer compelling evidence of a positive causal relationship between IIMs and LC, particularly with regard to lung squamous cell carcinoma, in the European population. Conversely, there is no evidence of LC causing IIMs. We recommend that LC diagnosis consider the specific characteristics of IIMs.

Ankylosing spondylitis: acute/subacute vs. chronic iridocyclitis - a bidirectional two-sample Mendelian randomization study.

Background: Observational studies found associations between ankylosing spondylitis (AS) and iridocyclitis (IC), but the causality remained unconfirmed. Methods: We employed two-sample Mendelian randomization (MR) to investigate the bidirectional causal relationships between AS and IC. Single-nucleotide polymorphisms (SNPs) were chosen from the FinnGen database's genome-wide association studies (GWAS) following a rigorous evaluation of the studies' quality. Sensitivity analysis was performed to assess the potential influence of pleiotropy and heterogeneity on the MR findings. Results: Elevated genetic risk for AS showed positive causal effects on IC and its subtypes (IC, OR = 1.094, 95% CI = 1.035-1.157, P = 0.00156; Acute/Subacute IC, OR = 1.327, 95% CI = 1.266-1.392, P = 8.73×10-32; Chronic IC, OR = 1.454, 95% CI = 1.308-1.618, P = 5.19×10-12). Significant causal association was specifically observed between Acute/Subacute IC and AS (OR = 1.944, 95% CI = 1.316-2.873, P = 8.38×10-4). Sensitivity analysis suggested that horizontal pleiotropy was unlikely to influence the causality, and the leave-one-out analysis confirmed that a single SNP did not drive the observed associations. Conclusion: Our findings provide new proof of a positive causal relationship between AS and IC in the European population. Notably, it is Acute/Subacute IC, rather than IC as a whole or Chronic IC, that is associated with an elevated risk of AS. These results emphasize the significance of considering AS characteristics in the diagnosis of Acute/Subacute IC.

Time-Resolved Four-Channel Jones Matrix Measurement of Birefringent Materials Using an Ultrafast Laser.

A method for ultrafast time-resolved four-channel Jones matrix measurement of birefringent materials using an ultrafast laser is investigated. This facilitated the acquisition of a four-channel angular multiplexing hologram in a single shot. The Jones matrix information of a birefringent sample was retrieved from the spatial spectrum of a hologram. The feasibility of this approach was established by measuring the Jones matrix of starch granules in microfluidic chips and the complex amplitude distribution and phase delay distribution of liquid crystal cell at different voltages. Moreover, when the picosecond laser was switched to a femtosecond laser, ultrafast measurements were possible provided that the time interval between two detection pulses was larger than the pulse width.

Simple system for realizing single-shot ultrafast sequential imaging based on spatial multiplexing in-line holography.

We present a simple system for realizing single-shot ultrafast sequential imaging based on spatial multiplexing in-line holography. In this system, we propose to combine a specially designed mini-reflector delay-line array with digital in-line holography. The former including a group of adjustable mini-reflectors can easily generate an array of probe sub-pulses that can be controlled independently in the propagation direction and time delays. The object beams formed by the different sub-pulses will propagate and fall on different recording regions of the image sensor to generate a single-shot spatial-multiplexing in-line hologram. The geometry of the digital in-line holography can simplify the complexity of the system and enable complex amplitude imaging. In addition, the time resolution of this system is limited only by the pulse duration, which allows this system to study the dynamic processes with the femtosecond order. In an experiment about the laser-induced air plasma, our proposed system achieves nine frames sequential holographic images with the frame rate of 7.5 trillion frames per second (Tfps).

Cylindrical wave-based off-axis digital holography with long field of view.

We present a new, to the best of our knowledge, type of off-axis digital holographic imaging method with a long field of view (FOV). In the method, the pre-magnification recording geometry is realized by a cylindrical lens (CL) or cylindrical beam instead of a conventional objective or spherical beam in traditional off-axis digital holography (DH). At the same time, the reference beam is replaced by a divergent cylindrical beam. Theoretical analysis and experiments have justified that, in off-axis DHs, the adoption of the cylindrical beams can realize a one-dimensional pre-magnification of the object beam only in the off-axis direction to satisfy the bandwidth constraint, and at the same time the FOV of the reconstructed image in the orthogonal direction can remain unaffected. In comparison with existing off-axis DHs, this cylindrical wave-based DH (CWDH) method has a distinct advantage in expanding the FOV of the reconstructed image. The FOV feature of the CWDH makes it especially suitable for applications that require a long FOV such as imaging samples in microfluidic channels.

SDF-1α Facilitates Mesenchymal Stem Cells to Induce Regulatory B Cell Differentiation from Patients with Immune Thrombocytopenia.

B cells play a central role in the pathogenesis of immune thrombocytopenia (ITP) by participating in humoral immunity. Meanwhile, regulatory B cells (Bregs), one subset of B cells, express negative regulatory effect on ITP. Mesenchymal stem cells (MSCs) have been demonstrated in the ability to induce immunosuppression, and stromal cell-derived factor-1α (SDF-1α) plays an important role in the migration and survival of MSCs. To investigate the mechanism of SDF-1α in controlling umbilical cord-derived MSCs (UC-MSCs) in inducing regulatory B cell differentiation of patients with ITP, we reconfirmed that SDF-1α promotes the proliferation of MSCs at the low doses of 0.05 µg/mL and 0.1 µg/mL but inhibits the proliferation and promotes the apoptosis of UC-MSCs at the high doses 0.5 µg/mL and 1 µg/mL; when UC-MSCs are cocultured with SDF-1α at 0.1 µg/mL, the decreased proportion of CD19+/CD24hi/CD38hi cells and IL-10-producing B cells (B 10 cell), considered as the Breg subset from ITP significantly enhanced, and the content of IL-10 in the supernatant is also obviously increased. The proportion of Bregs and the IL-10 secretion could be further promoted by the UC-MSCs treated with 0.1 µg/mL SDF-1α, which could also promote the miRNA-133 expression of UC-MSCs in an exosome-dependent manner; moreover, while the UC-MSCs were transfected with the miR-133 inhibitor, the proportion of induced Bregs decreased obviously when cocultured with peripheral blood mononuclear cells (PBMCs) of ITP. We conclude that UC-MSCs could effectively enhance the decreased proportion of Bregs from ITP; at appropriate concentrations, SDF-1α may promote the proliferating and survival ability of UC-MSCs and improve the production of Bregs induced by UC-MSCs through controlling miRNA-133 expression in the exosomes.

TNF Receptor: Fc Fusion Protein Downregulates RANKL/OPG Ratio by Inhibiting CXCL16/CXCR6 in Active Ankylosing Spondylitis.

BACKGROUND: Clinical studies indicate that recombinant tumor necrosis factor receptor:Fc fusion protein (rhTNFR:Fc) quickly alleviates symptoms and physical signs of active Ankylosing Spondylitis (AS), improving the manifestation of spinal inflammation on radiological imaging. However, the regulatory mechanism of rhTNFR:Fc in the chemokine pathway is unclear. Thus we study the mechanism of phlogogenic activity of CXCL16/CXCR6 in AS and the related mechanism of rhTNFR: Fc treatment. METHODS: Thirty-two cases of active AS were treated with rhTNFR:Fc for 3 consecutive months. Clinical response was evaluated at baseline and after treatment. CXCL16/CXCR6 expression as well as Receptor Activator Of Nuclear Factor-Κb Ligand (RANKL)/Osteoprotegerin (OPG), essential molecules for osteoclast differentiation, were studied in AS before and after treatment. Further, the proliferation of lymphocytes and the RANKL level stimulated by recombinant human CXCL16 (rhCXCL16) were measured in vitro. RESULTS: Thirty cases responded to rhTNFR:Fc treatment. The RANKL level, RANKL/OPG ratio, CXCLl6 level in serum, and CXCLl6 and CXCR6 mRNA levels in active AS were higher than those in controls and treated patients (P<0.001). rhCXCL16 treatment increased lymphocyte proliferation and RANKL level in active AS (P<0.001), but not in controls or treated patients (P>0.05). A positive linear correlation was noted between CXCL16 serum levels and RANKL/OPG ratio and between CXCL16 levels and C-reactive protein results (P<0.001). CONCLUSIONS: Our findings suggest that rhTNFR:Fc suppresses inflammation and bone destruction of AS by reducing the RANKL/OPG ratio through inhibition of the CXCL16/CXCR6 pathway.

Gout: a disease involved with complicated immunoinflammatory responses: a narrative review.

Gout is a disease with acute and/or chronic inflammation and tissue damage induced by the precipitation of monosodium urate crystal (MSU) crystals in bone joints, kidneys, and subcutaneous sites. In recent years, with the continuous research on gout animal models and patient clinical investigations, the mechanism of inflammation activation of gout has been further discovered. Studies have shown that pro-inflammatory factors such as interleukin (IL)-1ß, IL-8 and IL-17, NLRP3 inflammasome, and tumor necrosis factor alpha (TNF-α), anti-inflammatory factors such as IL-10, IL-37 are all involved in the MSU-induced gout inflammatory process. And the immune cells in gout, including neutrophils, monocytes/macrophages, and lymphocytes, all play important roles in the pathogenesis of gout. In this review, we mainly emphasize the understanding of various cytokines, inflammasome, and immune cells involved in the onset of gout, in order to provide a systematic and theoretical basis for the novel exploration of inflammatory therapeutic targets for gout.

Polarization holographic microscope slide for birefringence imaging of anisotropic samples in microfluidics.

Birefringence is an important optical property of anisotropic materials arising from anisotropies of tissue microstructures. Birefringence parameters have been found to be important to understand optical anisotropic architecture of many materials and polarization imaging has been applied in many researches in the field of biology and medicine. Here, we propose a scheme to miniaturize a double-channel polarization holographic interferometer optics to create a polarization holographic microscope slide (P-HMS) suitable for integrating with microfluidic lab-on-a-chip (LoC) systems. Based on the P-HMS combined with a simple reconstruction algorithm described in the paper, we can not only simultaneously realize holographic imaging of two orthogonal polarization components of dynamic samples in a microfluidic channel but also quantitative measurement of 2D birefringence information, both including the birefringence phase retardation and optic-axis orientation. This chip interferometer allows for off-axis double-channel polarization digital holographic recording using only a single illumination beam without need of any beam splitter or mirror. Its quasi-common path configuration and self-aligned design also make it tolerant to vibrations and misalignment. This work about the P-HMS could play a positive role in promoting the application of birefringence imaging in microfluidic LoC technology.

Single-shot ultrafast sequential holographic imaging with high temporal resolution and a large field of view.

A compact system for single-shot sequential holographic imaging (SSSHI) with high temporal resolution and a large field of view is proposed. In this system, a specially designed sequence pulse train generator with a group of diffractive gratings inserted is adopted to simultaneously generate the probe pulse train and the reference pulse train required for recording a single-shot spatial frequency division multiplexing hologram. The system successfully overcomes the walk-off effect of the ultrashort pulse laser in SSSHI and, hence, effectively avoids the influence of the short coherence of ultrashort pulses on the spatial resolution (or field of view) of SSSHI; the complexity of the system and the difficulty in the precise synchronous alignment of the probe and the reference pulses also can be greatly reduced. An experimental setup of the system was constructed, and a SSSHI of dynamical air plasmas induced by a femtosecond pulse laser is successfully realized.

Heparin and aspirin combination therapy restores T-cell phenotype in pregnant patients with antiphospholipid syndrome-related recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) is the most common manifestation of anti-phospholipid syndrome (APS), and activated CD4+ T cells are involved in its pathogenesis. Treatment with low-molecular weight heparin (LMWH) and aspirin combination improves pregnancy outcome, however, its mechanism of action is unclear. We investigated the effect of this therapy on Th1/Th2 cells in 89 patients with APS-RPL. The results showed that serum cytokine levels, T cell phenotypes, and transcription factors' gene expression levels representing Th1 responses were higher, whereas those representing Th2 responses were lower in patients with APS-RPL at the time of early pregnancy. This Th1-bias was reversed in patients who had live birth after receiving the combination therapy at the time of delivery. Patients with miscarriages continued to exhibit Th1-bias. In conclusion, these data support a role of Th1-bias in the pathogenesis of APS-RPL and suggest restoring T-cell phenotype as a new immunomodulatory mechanism of LMWH/aspirin combination.

Single-shot quantitative birefringence microscopy for imaging birefringence parameters.

A method for realizing 2D single-shot measurements of birefringence parameters (including both retardation and optic axis orientation) of anisotropic materials using a simple recording setup and an efficient processing algorithm is proposed. The recording setup can be built simply by inserting a circular polarizer and a polarization beam splitter, respectively, in the object path and reference path of a conventional off-axis holographic imaging system, with no need for other adjustments. An algorithm for quantitatively retrieving the birefringence parameters from one single-shot hologram is proposed and demonstrated, in which a new quantity describing the birefringence, called complex birefringence parameter, is introduced, and a set of formulas used to extract the birefringence parameters is derived. Some experimental results are given for demonstrating the feasibility of the method that reveal that the method may provide another effective approach for investigating the birefringence properties of dynamic anisotropic materials, especially the birefringence induced by ultrafast pulse lasers.

Quantitative phase imaging system with slightly-off-axis configuration and suitable for objects both larger and smaller than the size of the image sensor.

We propose a quantitative phase imaging system with exact slightly-off-axis configuration and suitable for objects both smaller and larger than the size of the effective recording region of the image sensors. In this system, the object is illuminated by a convergent spherical beam and a specially designed aperture filter is placed on the spatial frequency plane of the object wave; at the same time, a point source emitting from the edge of the aperture is taken as the reference beam, so that the optimal frequency condition for reconstruction of slightly-off-axis digital holograms can be always guaranteed for both large and small objects as well as different magnification (or the field of view) configurations. At the same time, a 1x2 single-mode optical fiber splitter is used for generating the reference and the illumination beams. Benefited from such fiber-based slightly-off-axis design, the proposed system provides a low-cost way to convert a regular microscope into a slightly-off-axis holographic one for microbiological specimens with a high spatial resolution.

Fracture healing in a collagen-induced arthritis rat model: Radiology and histology evidence.

This research was designed to investigate the fracture healing pattern in a rheumatoid arthritis (RA) rat model. A mid-shaft femur fracture (RA + F) model and normal fracture (NF) model as control were established. Micro-CT, H&E staining, TB staining, SO staining, tartrate-resistant acid phosphates, and immunohistochemistry test were performed. In the micro-CT images and H&E stains, fracture gaps were evident in the RA + F group 4 and 8 weeks after fracture. In detail, the bone mineral density, the ratio of bone volume to tissue volume, and trabecular thickness of the RA + F group were significantly lower than those of the NF group at all time points. Trabecular number value was significantly lower in the RA + F group 4 weeks after surgery in comparison with that of the NF group. Furthermore, the structure model index test result of the RA + F group was significantly higher than that of the NF group at all time points. TB staining and SO staining test results showed that the NF group had more cartilaginous callus in the earlier stage of bone healing process (4 weeks), and less cartilage callus formation in the later stage (8 weeks) in comparison with that of the RA + F group. Osteoclasts statistics score in the NF group were obviously lower than that of the RA + F group at all time points. MMP-3 and OPN protein levels of the fracture area in the RA + F group were significantly higher than those in the NF group. This study improves the understanding of the bone healing characteristics in patients with RA. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2876-2885, 2018.