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.

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.

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.

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.

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.

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.

A multicenter randomized open-label study of rituximab plus rhTPO vs rituximab in corticosteroid-resistant or relapsed ITP.

This study aimed to compare the efficacy and safety of rituximab (RTX) plus recombinant human thrombopoietin (rhTPO) with RTX alone in patients with immune thrombocytopenia (ITP) who had failed to respond to corticosteroids or relapsed. Recruited patients were randomized at a ratio of 2:1 into 2 groups: the combination group (RTX + rhTPO, n = 77) and the monotherapy group (RTX, n = 38). Overall response was achieved in 79.2% of patients in the combination group vs 71.1% in the monotherapy group (P = .36), and the complete response (CR) rate was 45.4% in the combination group compared with 23.7% in the monotherapy group (P = .026). The combination group had significantly shorter time to response (TTR; median and range, 7 and 4-28 days) compared with the monotherapy group (28 and 4-90 days) (P < .01). There was no difference between these 2 groups in terms of the long-term response (P = .12). Our findings demonstrated that the combination of RTX and rhTPO significantly increased the CR rate and shortened TTR compared with RTX monotherapy in the treatment of corticosteroid-resistant or relapsed ITP but failed to show a beneficial effect on the long-lasting response. This study is registered at www.clinicaltrials.gov as #NCT01525836.

Fiber-based lensless polarization holography for measuring Jones matrix parameters of polarization-sensitive materials.

We report a fiber-based lensless holographic imaging system to realize a single-shot measurement of two dimensional (2-D) Jones matrix parameters of polarization-sensitive materials. In this system, a multi-source lensless off-axis Fresnel holographic recording geometry is adopted, and two optical fiber splitters are used to generate the multiple reference and illumination beams required for recording a four-channel angular-multiplexing polarization hologram (AMPH). Using this system and the method described in this paper, spatially resolved Jones matrix parameters of a polarization-sensitive material can be retrieved from one single-shot AMPH. We demonstrate the feasibility of the method by extracting a 2-D Jones matrix of a composite polarizer. Applications of the method to measure the Jones matrix maps of a stressed polymethyl methacrylate sample and a mica fragment are also presented. Benefit from the fiber-based and lensless off-axis holographic design, the system possesses a quite compact configuration, which provides a feasible approach for development of an integrated and portable system to measure Jones matrix parameters of polarization-sensitive materials.

One-shot time-resolved holographic polarization microscopy for imaging laser-induced ultrafast phenomena.

A time-resolved holographic polarization microscopy, based on angular multiplexing holographic technique, is proposed for imaging ultrafast phenomena in polarization-sensitive transparent materials. This method can retrieve and image the complex amplitude distributions of two orthogonal polarization components of two sequential vector wavefronts with ultrashort time interval by a single short recording. Some experimental results for imaging the pulse laser induced ultrafast events based on the method are given. It is demonstrated that this technique may provide a potential tool for characterizing ultrafast processes in polarization-sensitive materials, especially in the non-reproducible experiment conditions.

Double-channel angular-multiplexing polarization holography with common-path and off-axis configuration.

We propose a double-channel angular-multiplexing polarization holographic imaging system with common-path and off-axis configurations. In the system, its input plane is spatially divided into three windows: an object window and two reference windows, and two orthogonal linear polarizers are attached, respectively, on the two reference windows; a two-dimensional cross grating is inserted between the input and output planes of the system. Thus the object beam passing through the object window and the two orthogonal polarized reference beams passing through the two reference windows can overlap each other at the output plane of the system and form a double-channel angular-multiplexing polarization hologram (DC-AM-PH). Using this system, the complex amplitude distributions of two orthogonal polarized components from an object can be recorded and reconstructed by one single-shot DC-AM-PH at the same time. Theoretical analysis and experimental results demonstrated that the system can be used to measure the Jones matrix parameters of polarization-sensitive or birefringent materials.

Wavefront sensing based on a spatial light modulator and incremental binary random sampling.

A wavefront sensing method based on a spatial light modulator (SLM) and an incremental binary random sampling (IBRS) algorithm is proposed. In this method, the recording setup is built just by a transmittance SLM and an image sensor. The tested wavefront incident to the SLM plane can be quantitatively retrieved from the diffraction intensities of the wavefront passed through the SLM displaying a IBRS pattern. Because only two modulation states (opaque and transparent) of the SLM are used, the method does not need to know the concrete modulation function of the SLM in advance. In addition by introducing the concept of the incremental random sampling into wavefront sensing, the adaptability of phase retrieving based on the diffraction intensities is significantly improved. To the best of our knowledge, no previous study has used this concept for the same purpose. Some experimental results are given for demonstrating the feasibility of our method.

Influence of lanthanide ion energy levels on luminescence of corresponding metalloporphyrins.

Lanthanide (Ln) porphyrins exhibit diverse luminescence properties that have not been fully explained yet. A series of Ln ions (Ln ions = La3+, Ce3+, Pr3+, Nd3+, Sm3+, Eu3+, Gd3+, Tb3+, Dy3+, Ho3+, Er3+, Tm3+, Yb3+, and Lu3+) were coordinated with hematoporphyrin monomethyl ether (HMME), and their luminescence properties and related differences were studied. Spectral analysis indicated that all Ln-HMMEs exhibit fluorescence emission. Gd- and Lu-HMMEs were the only lanthanide-HMMEs displaying strong molecular π-π room-temperature phosphorescence (RTP) with quantum yield ΦP > 10-3. Tb3+ can also induce RTP from HMME but ΦP of Tb-HMME is much smaller (ΦP ∼ 10-4). The observed luminescence property differences were analyzed in detail, focusing on the 4f energy levels of Ln ions. These levels mostly lie below the lowest singlet (S1) and triplet (T1) excited states of HMME, resulting in energy transfer from the T1 state in HMME to Ln ions and, therefore, in the absence of RTP from the corresponding metalloporphyrins. Gd3+ and Lu3+ are the only lanthanide ions not possessing such 4f energy levels, avoiding T1 quenching in Gd- and Lu-HMMEs. Although Tb3+ has low-lying 4f energy levels, the corresponding transition from the ground state is partly forbidden, resulting in weak energy transfer from HMME to Tb3+ that accounts for the low RTP quantum yield of the corresponding complex. Thus, our results indicate that the luminescence property differences of lanthanide porphyrins are due to the disparate energy levels of the Ln ions.

Curcumin modulation of the activation of PYK2 in peripheral blood mononuclear cells from patients with lupus nephritis.

INTRODUCTION: Proline-rich tyrosine kinase 2 (PYK2) provides important signals during the activation of lymphocytes, which is essential in autoimmune diseases. Systemic lupus erythematosus (SLE) is a representative autoimmune disease, and lupus nephritis (LN) is one of its most severe complications. Although glucocorticoid-binding immuno-suppression is the first-line therapy for patients with LN, the common and severe side effects of such treatment call for new strategies to improve long-term prognosis and life quality for these patients. Curcumin has been used to treat autoimmune disease with good curative effect, but little is known about the effect of curcumin on LN patients. Our aim was to investigate the mechanism of curcumin for management of LN, specifically regarding the PYK2 pathways. MATERIAL AND METHODS: Freshly isolated peripheral blood mononuclear cells (PBMCs) from 20 LN patients and 20 healthy individuals were cultured and stimulated with either PMA, PMA+TyrA9 (PYK2 specific inhibitor), or PMA+Curcumin, and with PBS as control. After 48 hours of incubation, cells were harvested and the expression of PYK2, p-PYK2, CD40L, CTLA-4, and PBMCs proliferation were measured. Then the expression and activation of PYK2 was evaluated using Western blot, the expression of costimulatory molecules CD40L and CTLA-4 protein was evaluated using flow cytometry, and PBMC proliferation was assessed using a [3H]-thymidine incorporation assay. RESULTS: Curcumin inhibited the expression and activation of PYK2 in PBMCs in patients with LN in vitro. The inhibition rate of curcumin was negatively correlated with the level of serum complement, but positively correlated with 24-h proteinuria. Curcumin also suppressed the expression of costimulatory molecules CD40L and CTLA-4, as well as PBMC proliferation. Interestingly, these effects were not reproduced on PBMC cultures of healthy subjects. CONCLUSIONS: The inhibition of PYK2 signalling protein may be one of the mechanisms underlying the action of curcumin in LN treatment.

Pulsed high-dose dexamethasone modulates Th1-/Th2-chemokine imbalance in immune thrombocytopenia.

BACKGROUND: Chemokines and chemokine receptors play important roles in autoimmune diseases; however, their role in immune thrombocytopenia (ITP) is unclear. High-dose dexamethasone (HD-DXM) may become a first-line therapy for adult patients with ITP, but the effect of HD-DXM on chemokines in ITP patients is unknown. Our aim was to investigate the mechanism of pulsed HD-DXM for management of ITP, specifically regarding the chemokine pathways. METHODS: Th1-/Th2-associated chemokine and chemokine receptor profiles in ITP patients before and after pulsed HD-DXM was studied. Plasma levels of CCL5 and CXCL11 (Th1-associated) and of CCL11 (Th2-associated) were determined by ELISA. Gene expression of these three chemokines and their corresponding receptors CCR5, CXCR3, and CCR3, in peripheral blood mononuclear cells (PBMCs) was determined by quantitative RT-PCR. RESULTS: Thirty-three of the thirty-eight ITP patients responded effectively to HD-DXM (oral, 40 mg/day, 4 days). In ITP patients, plasma CXCL11 levels increased, while CCL11 and CCL5 decreased compared to controls (P < 0.05). Similarly, gene expression of CXCL11 and its receptor CXCR3 increased, while CCL11 and CCR3 decreased (P < 0.05). CCL5 expression did not significantly change; however, expression of its receptor CCR5 increased (P < 0.05). Interestingly, in the patients who responded to pulsed HD-DXM, CXCL11 and CXCR3 expression was down-regulated, while CCL11 and CCR3 expression was up-regulated (P < 0.05). Meanwhile, CCL5 expression was up-regulated and CCR5 was down-regulated by HD-DXM (P < 0.05). CONCLUSIONS: The abnormal profiles of Th1-/Th2-associated chemokines and chemokine receptors may play important roles in the pathogenesis of ITP. Importantly, regulating Th1 polarization by pulsed HD-DXM may represent a novel approach for immunoregulation in ITP.

Thalidomide corrects impaired mesenchymal stem cell function in inducing tolerogenic DCs in patients with immune thrombocytopenia.

Thalidomide (THD) is an immunomodulatory agent used to treat immune-mediated diseases. Immune thrombocytopenia (ITP) is an autoimmune disorder in which impaired mesenchymal stem cells (MSCs) are potentially involved. We demonstrated that MSCs in ITP patients had reduced proliferative capacity and lost their immunosuppressive function, which could be corrected with THD treatment. According to the gene profile, the downregulation of caspase-8 and caspase-10, and upregulation of oct3/4 and tgf-ß1, may be associated with THD modulation. Dendritic cells (DCs) played an important role in mediating the inhibitory activity of MSCs. To study the functional alteration of DCs elicited by MSCs, we sorted DCs after incubation with MSCs and performed T-lymphocyte reaction assays. The THD-modulated MSCs from ITP patients induced mature DCs to become tolerogenic DCs, whereas unmodulated MSCs had no effect. The induction of tolerogenicity in DCs by MSCs was dependent on the expression of TIEG1 in DCs. The study reveals the inability of MSCs from ITP patients to induce tolerogenic ability in DCs. THD could restore the regulatory effect of MSCs on DCs. These findings will help us understand the pathogenesis of ITP, and with appropriate safeguards, THD may benefit patients with ITP.