Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study.

Belumosudil, an investigational oral selective inhibitor of Rho-associated coiled-coil-containing protein kinase 2 (ROCK2), reduces type 17 and follicular T helper cells via downregulation of STAT3 and enhances regulatory T cells via upregulation of STAT5. Belumosudil may effectively treat patients with chronic graft-versus-host disease (cGVHD), a major cause of morbidity and late nonrelapse mortality after an allogeneic hematopoietic cell transplant. This phase 2 randomized multicenter registration study evaluated belumosudil 200 mg daily (n = 66) and 200 mg twice daily (n = 66) in subjects with cGVHD who had received 2 to 5 prior lines of therapy. The primary end point was best overall response rate (ORR). Duration of response (DOR), changes in Lee Symptom Scale score, failure-free survival, corticosteroid dose reductions, and overall survival were also evaluated. Overall median follow-up was 14 months. The best ORR for belumosudil 200 mg daily and 200 mg twice daily was 74% (95% confidence interval [CI], 62-84) and 77% (95% CI, 65-87), respectively, with high response rates observed in all subgroups. All affected organs demonstrated complete responses. The median DOR was 54 weeks; 44% of subjects have remained on therapy for ≥1 year. Symptom reduction with belumosudil 200 mg daily and 200 mg twice daily was reported in 59% and 62% of subjects, respectively. Adverse events (AEs) were consistent with those expected in patients with cGVHD receiving corticosteroids and other immunosuppressants. Sixteen subjects (12%) discontinued belumosudil because of possible drug-related AEs. Belumosudil, a promising therapy for cGVHD, was well tolerated with clinically meaningful responses. This trial was registered at www.clinicaltrials.gov as #NCT03640481.

Wavefront-splitting interferometer based on orbital angular momentum beams.

Orbital angular momentum (OAM) interferometers have attracted great attention in metrology. However, OAM interferometers usually have large sizes and are difficult to align. OAM-based wavefront-splitting interferometer (WSI-OAM) can achieve nano-displacement measurement with compact size and easy to align. In this manuscript, we propose and demonstrate a nano-displacement measurement system based on WSI-OAM. A resolution of 0.1 nm with an uncertainty of 0.013 nm is achieved with measurement accuracy higher than 99.87% and linearity close to 99%. This work offers a practical approach to miniaturize and integrate OAM interferometers in metrology.

Accurate method for correcting the translation position error of ptychography based on quantum particle swarm optimization.

In ptychography, the translation position error will cause the periodic grid deviation and tremendously decrease the reconstruction quality. It is crucial to attain the precise translation position of the probe with respect to the object. The current correction methods may fall into a local optimal value, and miss the better results. An accurate method based on the quantum particle swarm optimization is proposed to globally correct the translation position error and add the randomness to avoid trapping in local optimum. In our proposed method, particles in a quantum bound state can appear at any point in the solution space with a certain probability density. In order words, the corrected translation position can be spread over the searching space, which can acquire the possibility of jumping out of the local optimum. Experiments are conducted to verify that our proposed method can be used to enhance the correction accuracy of the translation position error as well as avoid local optimum.

Phase retrieval for single-frame interferogram with an irregular-shaped aperture based on deep learning.

This paper proposes a high-precision phase retrieval method based on deep learning to extract the Zernike coefficients from a single-frame interferogram with an irregular-shaped aperture. Once the Zernike coefficients are obtained, the phase distribution can be retrieved directly using the Zernike polynomials. For many apertures, the root mean square (RMS) of the residual wavefront between the true and estimated wavefronts reached the order of 10-3 λ. Simulations were conducted under different noise conditions, indicating that the proposed method has high measurement accuracy and robustness. Experiments demonstrated that the accuracy achieved by this method was comparable to that of commercial phase-shifting interferometers. We believe that this method is useful for measuring optical surfaces with irregular apertures.

3D Printed High Performance Silver Mesh for Transparent Glass Heaters through Liquid Sacrificial Substrate Electric-Field-Driven Jet.

Transparent glass with metal mesh is considered a promising strategy for high performance transparent glass heaters (TGHs). However, the realization of simple, low-cost manufacture of high performance TGHs still faces great challenges. Here, a technique for the fabrication of high performance TGHs is proposed using liquid sacrificial substrate electric-field-driven (LS-EFD) microscale 3D printing of thick film silver paste. The liquid sacrificial substrate not only significantly improves the aspect ratio (AR) of silver mesh, but also plays a positive role in printing stability. The fabricated TGHs with a line width of 35 µm, thickness of 12.3 µm, and pitch of 1000 µm exhibit a desirable optoelectronic performance with sheet resistance (Rs ) of 0.195 Ω sq-1 and transmittance (T) of 88.97%. A successful deicing test showcases the feasibility and practicality of the manufactured TGHs. Moreover, an interface evaporator is developed for the coordination of photothermal and electrothermal systems based on the high performance TGHs. The vapor generation rate of the device reaches 10.69 kg m-2 h-1 with a voltage of 2 V. The proposed technique is a promising strategy for the cost-effective and simple fabrication of high performance TGHs.

Co-phase state detection for segmented mirrors by dual-wavelength optical vortex phase-shifting interferometry.

The application of large-aperture telescopes requires the support of co-phase measurement techniques for segmented mirrors. This paper proposes a novel method to detect the co-phase state of segmented mirrors by applying a dual-wavelength phase-shifting interferometer based on optical vortex. Theory and experiments indicate that the wrapped phase map edges obtained by phase-shifting interference of the vortex beam are distributed in the form of a Fermat spiral. The piston error of the segmented mirrors corresponds to the rotation of the standard Fermat spiral center. In contrast, the tip/tilt error corresponds to the alteration of the center position of the deformed Fermat spiral. The rotation angle and the center position of the spiral are obtained by curve fitting, and the co-phase errors can be inversely solved. The experiments achieved an accuracy of approximately 4.04 nm in the piston and 0.16″ in the tip/tilt. The method avoids using complex lens arrays and devices, has an extended measurement range, high accuracy, and allows the co-phase errors between all sub-mirrors to be obtained in real-time. This study provides a novel and general method for detecting co-phase errors in a segmented primary mirror.

Imaging performance of a mid-infrared metalens with a machining error.

Metalenses exhibit excellent performance as a new type of optical element; mid-infrared devices based on metalenses are advantageous to numerous applications in biomedical, military and industrial fields. The demand for large-area and high-efficiency mid-infrared metalenses has increased in recent years. However, the current processing methods for metalens production introduce different types of processing errors. Therefore, qualitative analyses of various errors that may exist in the processing of metalenses should be performed. In this study, we use the finite-difference time-domain calculation method and introduce various typical errors into a transmission phase-based mid-infrared metalens for simulation and analysis. The simulation results show that the defects caused by these processes affect focusing efficiency, and that some defects affect the quality of light. Subsequently, we prepare a metalens within the allowable error range and test its optical performances. The experiment confirms the excellent imaging performance of our metalens. Our study can help manufacturers identify defects to improve manufacturing processes, thereby enabling the incorporation of metalenses in industrial applications.

Vector soliton dynamics in a high-repetition-rate fiber laser.

The existence of vector solitons that arise from the birefringence nature of optical fibers has been increasingly of interest for the stability of mode-locked fiber lasers, particularly for those operating in the high-fundamental-repetition-rate regime, where a large amount of fiber birefringence is required to restore the phase relation between the orthogonally polarized vector solitons, resulting in stable mode-locking free of polarization rotation. These vector solitons can exhibit diverse time-varying polarization dynamics, which prevent industrial and scientific applications requiring stable and uniform pulse trains at high fundamental repetition rates. This pressing issue, however, has so far been rarely studied. To this end, here we theoretically and experimentally dissect the formation of vector solitons in a GHz-repetition-rate fiber laser and investigate effective methods for suppressing roundtrip-to-roundtrip polarization dynamics. Our numerical model can predict both dynamic and stable regimes of high-repetition-rate mode-locking by varying the amount of fiber birefringence, resulting in the polarization rotation vector soliton (PRVS) and linearly polarized soliton (LPS), respectively. These dynamic behaviors are further studied by using an analytical approach. Interestingly, our theoretical results indicate a cavity-induced locking effect, which can be a complementary soliton trapping mechanism for the co-propagating solitons. Finally, these theoretical predications are experimentally verified, and we obtain both PRVS and LPS by adjusting the intracavity fiber birefringence.

Spurious fringe processing for dielectric metasurface profile measurement using white-light scanning interferometry.

Dielectric metasurfaces, which are capable of manipulating incident light, have been a novel branch of flat optics. This modulation ability is realized by nanostructures with space-variant geometrical parameters such as height and diameter. Therefore, accurate profile measurement of metasurfaces is of great importance. White-light scanning interferometry is widely used for profile measurement. The step height is retrieved by locating the envelope's peak. However, spurious fringes attached to the desired fringes were observed at the measured area near the edge of nanostructures. Their amplitude distributions vary with the density of nanostructures as well as distance to the edge. Further, anomalous coherence signals with two fringe envelopes are produced, which result in inaccurate measurement results. We attributed this phenomenon to the complex light modulation by the nanostructures. When referring to the anomalous coherence signals for the top of the nanostructures, one envelope is produced by the top, and the other is produced by the bottom; however, it is difficult to distinguish these two, which is the same case for the bottom of the nanostructures. To automatically solve these obstacles, a signal processing method, which integrates the image segmentation technology to identify and divide the anomalous coherence signals, along with a Morlet wavelet transform to extract the fringe envelope, suitable for any measured area of the dielectric metasurface, is proposed. One metasurface belt consisting of seven kinds of nanopillars with varying arrayed densities that produce different coherence signals is measured. The diameter distribution ranges from 500 to 1250 nm with a constant height of 1850 nm. The local periods in the X and Y directions are 3020 and 1740 nm, respectively. Measurement results demonstrate the validity of the proposed method for spurious fringes processing.

Accelerated convergence extended ptychographical iterative engine using multiple axial intensity constraints.

The extended ptychographical iterative engine (ePIE) is widely applied in the field of ptychographic imaging due to its great flexibility and computational efficiency. A technique of ePIE with multiple axial intensity constraints, which is called MAIC-PIE, is proposed to drastically improve the convergence speed and reduce the calculation time. This technique requires that the diffracted light from the sample is propagated to the multiple individual axial planes, which can be achieved by using the beam splitter and multiple CCDs. In this technique, an additional intensity constraint is involved in the iterative process that makes for building the reasonable guesses of the probe and object in the first few iterations and accelerating the convergence. Simulations and experiments have verified that MAIC-PIE behaves good performance with fast convergence. The great performance and limited computational complexity make it a very attractive and promising technique for ptychographic imaging.

Generalized shift-rotation absolute measurement method for optical surface shapes with polygonal apertures based on migration recognition by Radon transform.

A generalized shift-rotation absolute measurement method for optical surface shapes with polygonal apertures based on migration recognition by Radon transform is proposed. The rotation angles and translation distances of the test surface, measured three times, are calculated through migration recognition. The absolute shape of the test surface with the polygonal aperture is fitted by orthogonal Zernike polynomials. Compared to the existing absolute measurement method for polygonal apertures, our method ensures test surface measurement accuracy without high-precision attitude control and repeated adjustments. The measurement is simple and coherent, which reduces the measurement time and improves the efficiency.

Metal-Free Oxidative B-N Coupling of nido-Carborane with N-Heterocycles.

A general method for the oxidative substitution of nido-carborane (7,8-C2 B9 H12 - ) with N-heterocycles has been developed by using 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) as an oxidant. This metal-free B-N coupling strategy, in both inter- and intramolecular fashions, gave rise to a wide array of charge-compensated, boron-substituted nido-carboranes in high yields (up to 97 %) with excellent functional-group tolerance under mild reaction conditions. The reaction mechanism was investigated by density-functional theory (DFT) calculations. A successive single-electron transfer (SET), B-H hydrogen-atom transfer (HAT), and nucleophilic attack pathway is proposed. This method provides a new approach to nitrogen-containing carboranes with potential applications in medicine and materials.

Generalized shift-rotation absolute measurement method for high-numerical-aperture spherical surfaces with global optimized wavefront reconstruction algorithm.

In this paper, a generalized shift-rotation absolute measurement method is proposed to measure the absolute surface shape of high-numerical-aperture spherical surfaces. Based on the wavefront difference method, the high order misalignment aberrations can be removed from the measurements. Our generalized shift-rotation absolute measurement process only needs one rotational measurement position and one translational measurement position. A wavefront reconstruction method based on the self-adaptive differential evolution algorithm is proposed to calculate the Zernike polynomials coefficient ai of the absolute surface shape Wtest(x,y), the rotation angle Δθ, the translation δx along the x axis, and the translation δy along the y axis. The translation error and rotation error in other absolute measurement methods are avoided using our generalized shift-rotation absolute measurement method. Experimental absolute results of the test surface and reference surface are given and the difference of reference surface shapes between two testings in experiments is 0.12 nm root mean square.

Fibrillatory wave amplitude on transesophageal ECG as a marker of left atrial low-voltage areas in patients with persistent atrial fibrillation.

BACKGROUND: Low-voltage areas (LVAs) are frequently observed in patients with persistent atrial fibrillation (PeAF) and may represent adverse atrial remodeling. However, noninvasive method of evaluating LAVs is not well established. METHODS: In a cohort of 68 patients with PeAF, endocardial voltage maps of left atrium (LA) were created during sinus rhythm after pulmonary vein isolation (PVI). LVAs were defined as areas with electrogram amplitudes <0.5 mV. LA-LVAs were correlated with clinical, echocardiographic, surface, and transesophageal electrocardiography (TE-ECG) variables. RESULTS: LA voltage mapping revealed any degree of LA-LVAs in 50 (73.5%) patients. Patients with LA-LVAs were older, had a longer history of AF, and lower fibrillatory wave (F wave) amplitude on TE-ECG (0.27 ± 0.06 vs 0.39 ± 0.08 mv, p < .01) as compared to patients without LA-LVAs. The extent of LA-LVAs was weakly correlated with age (R = 0.36, p = .03) and AF duration (R = 0.26, p = .02), but significantly correlated with F-wave amplitude on TE-ECG (R = -0.57, p < .01). Only F-wave amplitude on TE-ECG was found as independent predictor for the presence of LA-LVAs (OR = 1.53, 95% CI = 1.09-2.96, p = .03). A receiver operating characteristic (ROC) curve identified an F-wave amplitude of 0.29 mV (AUC = 0.788; sensitivity = 68.4%; specificity = 73.2%) on TE-ECG as the optimal cutoff value for predicting LA-LVAs. CONCLUSIONS: As a noninvasive investigation, F-wave amplitude on TE-ECG may be used as an indicator for the presence of LA-LVAs.

Predictive value of exercise-induced atrial natriuretic peptide secretion for the presence of left atrial low-voltage areas in patients with persistent atrial fibrillation.

Objectives Left atrial (LA) low-voltage areas (LVAs) are a strong predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). However, a non-invasive method for evaluating LA-LAVs has not been established yet. The objective of our study was to assess the predictive value of the plasma atrial natriuretic peptide (ANP) level for the presence of LA-LVAs in patients with persistent AF (PeAF). Methods Seventy-two PeAF patients underwent an exercise stress test preprocedurally. LA voltage maps were created after PVI. Demographic, clinical and echocardiographic data were recorded. Plasma levels of ANP at baseline (ANP0) and increase induced by exercise (ΔANP) were also measured. Results Compared with patients without LA-LVAs, patients with LA-LVAs had a longer history of AF, higher CHADS2 score and higher ANP0 and lower ΔANP. LA-LVAs extent correlated with duration of AF history, CHADS2 score and ΔANP (R = -0.76, P < 0.01). Only ΔANP independently predicted the presence of LA-LVAs (OR =1.63, P = 0.02). Derived from the ROC curve, ΔANP <55 pg/mL predicted the presence of LA-LVAs with high accuracy (AUC =0.78; 95% CI =0.57-0.87, P < 0.01). Conclusions Exercise-induced secretion of ANP may be used to predict the presence of LA-LVAs in patients with PeAF before catheter ablation.

Large radius of curvature measurement based on virtual quadratic Newton rings phase-shifting moiré-fringes measurement method in a nonnull interferometer.

We have proposed a virtual quadratic Newton rings phase-shifting moiré-fringes measurement method in a nonnull interferometer to measure the large radius of curvature for a spherical surface. In a quadratic polar coordinate system, linear carrier testing Newton rings interferogram and virtual Newton rings interferogram form the moiré fringes. It is possible to retrieve the wavefront difference data between the testing and standard spherical surface from the moiré fringes after low-pass filtering. Based on the wavefront difference data, we deduced a precise formula to calculate the radius of curvature in the quadratic polar coordinate system. We calculated the retrace error in the nonnull interferometer using the multi-configuration model of the nonnull interferometric system in ZEMAX. Our experimental results indicate that the measurement accuracy is better than 0.18% for a spherical mirror with a radius of curvature of 41,400 mm.

Focal length measurement based on the wavefront difference method by a Fizeau interferometer.

A method for measuring the focal length of the lens by a Fizeau interferometer is proposed. Based on the Gaussian imaging equation and the longitudinal displacements of the object point and image point, a precise formula for focal length calculation is deduced. The longitudinal displacement of the object points is determined by the wavefront difference method with a subnanometer resolution. An experimental system for focal length measurements is set up to verify the principle. The sources of uncertainty in measurement are discussed. Both the positive and negative lens experimental results indicate that the measurement accuracy is less than 0.16% under normal experimental environment.

Exploring the Therapeutic Potential of 5-Fluorouracil-Loaded Calcium Carbonate Nanoparticles Combined with Natural Compound Thymoquinone for Colon Cancer Treatment.

Given the need for novel and effective therapies for colon cancer, this study aimed to investigate the effects of 5-fluorouracil-loaded calcium carbonate nanoparticles (5FU-CaCO3np) combined with thymoquinone (TQ) against colon cancer. A shaking incubator and a high-speed homogenizer were used to prepare the optimal 5FU-CaCO3np, with characterizations of physicochemical properties, in vitro drug release profile, and biocompatibility. In vitro experiments and molecular docking were employed to evaluate the therapeutic potential of the combination for colon cancer treatment. Study results revealed that 5FU-CaCO3np with a size of approximately 130 nm was synthesized using the high-speed homogenizer. Its favorable biocompatibility, pH sensitivity, and sustained release properties facilitated reduced toxic side effects of 5-FU on NIH3T3 normal cells and enhanced inhibitory effects on CT26 colon cancer cells. The combination of 5FU-CaCO3np (1.875 µM) and TQ (30 µM) showed significantly superior anti-colon cancer effects to 5FU-CaCO3np alone in terms of cell proliferation and migration inhibition, cell apoptosis induction, and spheroid growth suppression in CT26 cells (p < 0.05), with strong interactions between the drugs and targets (E-cadherin, Bcl-2, PCNA, and MMP-2). These results provide evidence for 5FU-CaCO3np as a novel regimen against colon cancer. Combining 5FU-CaCO3np and TQ may offer a new perspective for colon cancer therapy.

Unveiling Drimenol: A Phytochemical with Multifaceted Bioactivities.

Drimenol, a phytochemical with a distinct odor is found in edible aromatic plants, such as Polygonum minus (known as kesum in Malaysia) and Drimys winteri. Recently, drimenol has received increasing attention owing to its diverse biological activities. This review offers the first extensive overview of drimenol, covering its sources, bioactivities, and derivatives. Notably, drimenol possesses a wide spectrum of biological activities, including antifungal, antibacterial, anti-insect, antiparasitic, cytotoxic, anticancer, and antioxidant effects. Moreover, some mechanisms of its activities, such as its antifungal effects against human mycoses and anticancer activities, have been investigated. However, there are still several crucial issues in the research on drimenol, such as the lack of experimental understanding of its pharmacokinetics, bioavailability, and toxicity. By synthesizing current research findings, this review aims to present a holistic understanding of drimenol, paving the way for future studies and its potential utilization in diverse fields.

5-Fluorouracil in Combination with Calcium Carbonate Nanoparticles Loaded with Antioxidant Thymoquinone against Colon Cancer: Synergistically Therapeutic Potential and Underlying Molecular Mechanism.

Colon cancer is the third most common cancer worldwide, with high mortality. Adverse side effects and chemoresistance of the first-line chemotherapy 5-fluorouracil (5-FU) have promoted the widespread use of combination therapies. Thymoquinone (TQ) is a natural compound with potent antioxidant activity. Loading antioxidants into nano delivery systems has been a major advance in enhancing their bioavailability to improve clinical application. Hence, this study aimed to prepare the optimal TQ-loaded calcium carbonate nanoparticles (TQ-CaCO3 NPs) and investigate their therapeutic potential and underlying molecular mechanisms of TQ-CaCO3 NPs in combination with 5-FU against colon cancer. Firstly, we developed purely aragonite CaCO3 NPs with a facile mechanical ball-milling method. The pH-sensitive and biocompatible TQ-CaCO3 NPs with sustained release properties were prepared using the optimal synthesized method (a high-speed homogenizer). The in vitro study revealed that the combination of TQ-CaCO3 NPs (15 µM) and 5-FU (7.5 µM) inhibited CT26 cell proliferation and migration, induced cell apoptosis and cell cycle arrest in the G0/G1 phase, and suppressed the CT26 spheroid growth, exhibiting a synergistic effect. Finally, network pharmacology and molecular docking results indicated the potential targets and crucial signaling pathways of TQ-CaCO3 NPs in combination with 5-FU against colon cancer. Therefore, TQ-CaCO3 NPs combined with 5-FU could enhance the anti-colon cancer effects of 5-FU with broader therapeutic targets, warranting further application for colon cancer treatment.