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.

Intranasal Delivery of Curcumin Nanoparticles Improves Neuroinflammation and Neurological Deficits in Mice with Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) represents one of the most severe subtypes of stroke. Due to the complexity of the brain injury mechanisms following ICH, there are currently no effective treatments to significantly improve patient functional outcomes. Curcumin, as a potential therapeutic agent for ICH, is limited by its poor water solubility and oral bioavailability. In this study, mPEG-PCL is used to encapsulate curcumin, forming curcumin nanoparticles, and utilized the intranasal administration route to directly deliver curcumin nanoparticles from the nasal cavity to the brain. By inhibiting pro-inflammatory neuroinflammation of microglia following ICH in mice, reprogramming pro-inflammatory microglia toward an anti-inflammatory function, and consequently reducing neuronal inflammatory death and hematoma volume, this approach improved blood-brain barrier damage in ICH mice and promoted the recovery of neurological function post-stroke. This study offers a promising therapeutic strategy for ICH to mediate neuroinflammatory microenvironments.

An end-to-end workflow for nondestructive 3D pathology.

Recent advances in 3D pathology offer the ability to image orders of magnitude more tissue than conventional pathology methods while also providing a volumetric context that is not achievable with 2D tissue sections, and all without requiring destructive tissue sectioning. Generating high-quality 3D pathology datasets on a consistent basis, however, is not trivial and requires careful attention to a series of details during tissue preparation, imaging and initial data processing, as well as iterative optimization of the entire process. Here, we provide an end-to-end procedure covering all aspects of a 3D pathology workflow (using light-sheet microscopy as an illustrative imaging platform) with sufficient detail to perform well-controlled preclinical and clinical studies. Although 3D pathology is compatible with diverse staining protocols and computationally generated color palettes for visual analysis, this protocol focuses on the use of a fluorescent analog of hematoxylin and eosin, which remains the most common stain used for gold-standard pathological reports. We present our guidelines for a broad range of end users (e.g., biologists, clinical researchers and engineers) in a simple format. The end-to-end workflow requires 3-6 d to complete, bearing in mind that data analysis may take longer.

Nanodelivery Systems as a Novel Strategy to Overcome Treatment Failure of Cancer.

Despite the tremendous progress in cancer treatment in recent decades, cancers often become resistant due to multiple mechanisms, such as intrinsic or acquired multidrug resistance, which leads to unsatisfactory treatment effects or accompanying metastasis and recurrence, ultimately to treatment failure. With a deeper understanding of the molecular mechanisms of tumors, researchers have realized that treatment designs targeting tumor resistance mechanisms would be a promising strategy to break the therapeutic deadlock. Nanodelivery systems have excellent physicochemical properties, including highly efficient tissue-specific delivery, substantial specific surface area, and controllable surface chemistry, which endow nanodelivery systems with capabilities such as precise targeting, deep penetration, responsive drug release, multidrug codelivery, and multimodal synergy, which are currently widely used in biomedical researches and bring a new dawn for overcoming cancer resistance. Based on the mechanisms of tumor therapeutic resistance, this review summarizes the research progress of nanodelivery systems for overcoming tumor resistance to improve therapeutic efficacy in recent years and offers prospects and challenges of the application of nanodelivery systems for overcoming cancer resistance.

An end-to-end workflow for non-destructive 3D pathology.

Recent advances in 3D pathology offer the ability to image orders-of-magnitude more tissue than conventional pathology while providing a volumetric context that is lacking with 2D tissue sections, all without requiring destructive tissue sectioning. Generating high-quality 3D pathology datasets on a consistent basis is non-trivial, requiring careful attention to many details regarding tissue preparation, imaging, and data/image processing in an iterative process. Here we provide an end-to-end protocol covering all aspects of a 3D pathology workflow (using light-sheet microscopy as an illustrative imaging platform) with sufficient detail to perform well-controlled preclinical and clinical studies. While 3D pathology is compatible with diverse staining protocols and computationally generated color palettes for visual analysis, this protocol will focus on a fluorescent analog of hematoxylin and eosin (H&E), which remains the most common stain for gold-standard diagnostic determinations. We present our guidelines for a broad range of end-users (e.g., biologists, clinical researchers, and engineers) in a simple tutorial format.

Nondestructive 3D pathology with analysis of nuclear features for prostate cancer risk assessment.

Prostate cancer treatment decisions rely heavily on subjective visual interpretation [assigning Gleason patterns or International Society of Urological Pathology (ISUP) grade groups] of limited numbers of two-dimensional (2D) histology sections. Under this paradigm, interobserver variance is high, with ISUP grades not correlating well with outcome for individual patients, and this contributes to the over- and undertreatment of patients. Recent studies have demonstrated improved prognostication of prostate cancer outcomes based on computational analyses of glands and nuclei within 2D whole slide images. Our group has also shown that the computational analysis of three-dimensional (3D) glandular features, extracted from 3D pathology datasets of whole intact biopsies, can allow for improved recurrence prediction compared to corresponding 2D features. Here we seek to expand on these prior studies by exploring the prognostic value of 3D shape-based nuclear features in prostate cancer (e.g. nuclear size, sphericity). 3D pathology datasets were generated using open-top light-sheet (OTLS) microscopy of 102 cancer-containing biopsies extracted ex vivo from the prostatectomy specimens of 46 patients. A deep learning-based workflow was developed for 3D nuclear segmentation within the glandular epithelium versus stromal regions of the biopsies. 3D shape-based nuclear features were extracted, and a nested cross-validation scheme was used to train a supervised machine classifier based on 5-year biochemical recurrence (BCR) outcomes. Nuclear features of the glandular epithelium were found to be more prognostic than stromal cell nuclear features (area under the ROC curve [AUC] = 0.72 versus 0.63). 3D shape-based nuclear features of the glandular epithelium were also more strongly associated with the risk of BCR than analogous 2D features (AUC = 0.72 versus 0.62). The results of this preliminary investigation suggest that 3D shape-based nuclear features are associated with prostate cancer aggressiveness and could be of value for the development of decision-support tools. © 2023 The Pathological Society of Great Britain and Ireland.

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).

A hybrid open-top light-sheet microscope for versatile multi-scale imaging of cleared tissues.

Light-sheet microscopy has emerged as the preferred means for high-throughput volumetric imaging of cleared tissues. However, there is a need for a flexible system that can address imaging applications with varied requirements in terms of resolution, sample size, tissue-clearing protocol, and transparent sample-holder material. Here, we present a 'hybrid' system that combines a unique non-orthogonal dual-objective and conventional (orthogonal) open-top light-sheet (OTLS) architecture for versatile multi-scale volumetric imaging. We demonstrate efficient screening and targeted sub-micrometer imaging of sparse axons within an intact, cleared mouse brain. The same system enables high-throughput automated imaging of multiple specimens, as spotlighted by a quantitative multi-scale analysis of brain metastases. Compared with existing academic and commercial light-sheet microscopy systems, our hybrid OTLS system provides a unique combination of versatility and performance necessary to satisfy the diverse requirements of a growing number of cleared-tissue imaging applications.

Bottom slag-to-flue gas controls on S and Cl from co-combustion of textile dyeing sludge and waste biochar: Their interactions with temperature, atmosphere, and blend ratio.

S and Cl distribution patterns and their evolution pathways were quantified during the co-combustions of textile dyeing sludge (TDS) and waste biochar (BC). S in the flue gas rose from 10.60% at 700 °C to 45.09% at 1000 °C for the mono-combustion of TDS in the air atmosphere. At 1000 °C, S in the bottom slag and flue gas grew by 2.65% and fell by 2.11%, respectively, for the TDS mono-combustion in the 30%O2/70%CO2 atmosphere. The 40% BC addition increased the S retention in the bottom slag by 30.39% and decreased its release to the flue gas by 34.50% by changing the evolution of CaSO4 and enabling more K to fix S as K2SO4. The decomposition of inorganic Cl was the main source of the Cl-containing gases. The 20%O2/80%CO2 atmosphere (36.29%) and 40% BC addition (27.26%) had higher Cl in the bottom slag than did TDS mono-combusted at 1000 °C (25.60%) by inhibiting the decomposition of organic Cl. Our study provides insights into the co-combustion of TDS and BC and controls on S and Cl for a cleaner production. Future research remains to conducted to verify scale-up experiments.

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.

Prostate Cancer Risk Stratification via Nondestructive 3D Pathology with Deep Learning-Assisted Gland Analysis.

Prostate cancer treatment planning is largely dependent upon examination of core-needle biopsies. The microscopic architecture of the prostate glands forms the basis for prognostic grading by pathologists. Interpretation of these convoluted three-dimensional (3D) glandular structures via visual inspection of a limited number of two-dimensional (2D) histology sections is often unreliable, which contributes to the under- and overtreatment of patients. To improve risk assessment and treatment decisions, we have developed a workflow for nondestructive 3D pathology and computational analysis of whole prostate biopsies labeled with a rapid and inexpensive fluorescent analogue of standard hematoxylin and eosin (H&E) staining. This analysis is based on interpretable glandular features and is facilitated by the development of image translation-assisted segmentation in 3D (ITAS3D). ITAS3D is a generalizable deep learning-based strategy that enables tissue microstructures to be volumetrically segmented in an annotation-free and objective (biomarker-based) manner without requiring immunolabeling. As a preliminary demonstration of the translational value of a computational 3D versus a computational 2D pathology approach, we imaged 300 ex vivo biopsies extracted from 50 archived radical prostatectomy specimens, of which, 118 biopsies contained cancer. The 3D glandular features in cancer biopsies were superior to corresponding 2D features for risk stratification of patients with low- to intermediate-risk prostate cancer based on their clinical biochemical recurrence outcomes. The results of this study support the use of computational 3D pathology for guiding the clinical management of prostate cancer. SIGNIFICANCE: An end-to-end pipeline for deep learning-assisted computational 3D histology analysis of whole prostate biopsies shows that nondestructive 3D pathology has the potential to enable superior prognostic stratification of patients with prostate cancer.

Evaluation of GnRH antagonist pretreatment before ovarian stimulation in a GnRH antagonist protocol in normal ovulatory women undergoing IVF/ICSI: a randomized controlled trial.

BACKGROUND: Synchronization of follicles is key to improving ovulation stimulation with the gonadotropin-releasing hormone (GnRH) antagonist protocol. GnRH antagonist administration in the early follicular phase can quickly decrease gonadotrophin (Gn) levels and achieve downregulation before stimulation, which may improves synchronization. A previous small randomized controlled study (RCT) showed that pretreatment with a GnRH antagonist for 3 days before stimulation may increase oocyte retrieval but cannot increase the pregnancy rate. This study investigated whether the GnRH antagonist pretreatment protocol in ovulatory women can increase the synchronization of follicles and pregnancy outcomes compared with the conventional GnRH antagonist protocol. METHODS: This RCT included 136 normal ovulatory women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Both groups were treated with recombinant follicle-stimulating hormone (r-FSH) and a flexible GnRH antagonist protocol. The women were randomized into two equal groups with or without GnRH antagonist administration from day 2 of the menstrual cycle for 3 days before stimulation. Our primary outcome was the number of retrieved oocytes. Secondary outcomes included the pregnancy rate and live birth rate. RESULTS: Both groups had similar baseline characteristics. The number of retrieved oocytes in the study group was comparable to that in the control group (9.5 [8.0-13.0] vs. 11.0 [7.0-14.8], P = 0.469). There was no significant difference in the follicle size. The fertilization rate, number of good-quality embryos, implantation rate, pregnancy rate, ongoing pregnancy rate, live birth rate per embryonic transfer cycle, and miscarriage rate were similar between the two groups. CONCLUSION: This large RCT analysed GnRH antagonist pretreatment with the GnRH antagonist protocol applied to normal ovulatory women undergoing IVF/ICSI. The number of retrieved oocytes and pregnancy outcomes did not significantly vary. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800019730 . Registered 26 November 2018.

Multiple drivers, interaction effects, and trade-offs of efficient and cleaner combustion of torrefied water hyacinth.

Developing cleaner and affordable alternatives to the sole reliance on fossil fuels has intensified efforts to improve the thermochemical conversion property of the second-generation lignocellulosic biomass. This study aimed to explore the effects of the two torrefaction temperatures (200 and 300 °C), the two reaction atmospheres (N2/O2 and CO2/O2), and the three heating rates (5, 10, and 15 °C/min) on the combustion regime of water hyacinth (WH). Decomposition behaviors, reaction kinetics, thermodynamics, and mechanisms, evolved emissions and functional groups, and fuel microstructure properties were quantified. The deoxygenation and dehydration reactions acted as the main drivers of the torrefaction process, with the peak degree of deoxygenation of 86.21% for WH torrefied at 300 °C (WH300). WH300 significantly reduced the quantity of oxygen-containing functional groups and altered the fuel microstructure properties. The order of the decomposition rates of the pseudo-components were hemicellulose > cellulose > lignin for both WH and WH torrefied at 200 °C (WH200) and cellulose > lignin > hemicellulose for WH300. The average activation energy fell from 197.71 to 195.71 kJ/mol for WH, 287.90 to 195.97 kJ/mol for WH200, and 226.92 to 184.94 kJ/mol for WH300 when the atmosphere changed from N2/O2 to CO2/O2. The heating rate exerted a stronger control on their combustion behaviors than did the reaction atmosphere. CO2, NO, and NO2 emissions dropped by 46.0, 53.1, and 65.9% for WH200 and 29.6, 42.8, and 62.5% for WH300, respectively, when compared to WH. 473.7 °C, 5 °C/min, and the CO2/O2 atmosphere were the optimal settings for the maximized combustion efficiency. 717.1 °C was determined as the optimal setting for the minimized combustion emissions. Our study can yield new insights into the large-scale and cleaner combustion of the torrefied water hyacinth.

Multi-resolution open-top light-sheet microscopy to enable efficient 3D pathology workflows.

Open-top light-sheet (OTLS) microscopes have been developed for user-friendly and versatile high-throughput 3D microscopy of thick specimens. As with all imaging modalities, spatial resolution trades off with imaging and analysis times. A hierarchical multi-scale imaging workflow would therefore be of value for many volumetric microscopy applications. We describe a compact multi-resolution OTLS microscope, enabled by a novel solid immersion meniscus lens (SIMlens), which allows users to rapidly transition between air-based objectives for low- and high-resolution 3D imaging. We demonstrate the utility of this system by showcasing an efficient 3D analysis workflow for a diagnostic pathology application.

Combustion parameters, evolved gases, reaction mechanisms, and ash mineral behaviors of durian shells: A comprehensive characterization and joint-optimization.

In this work, the characteristic parameters, evolved gases, reaction mechanisms, and ash conversions of the durian shell (DS) combustion were quantified coupling thermogravimetry, mass spectroscopy, Fourier transform infrared spectroscopy, and X-ray fluorescence spectra analyses. The main stage of the DS combustion occurred between 130.2 and 481.9 °C. Its activation energy value estimated by the three model-free methods ranged from 192.82 to 213.24 kJ/mol. The average enthalpy, entropy and Gibbs free energy changes were in the ranges of 177.74-178.47 kJ/mol, 32.00-34.25 J/(mol·K), and 200.79-207.74 kJ/mol, respectively. The third-order (F3) model best described its most likely reaction mechanism. The main evolved gas was CO2, with no SO2 emission. The ash from the DS combustion belonged to K-type ash. 618 °C and 8 K/min were determined as the optimal operation conditions to jointly optimize the multiple targets of the combustion responses.

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.

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.

A 2.5 mW/ch, 50 Mcps, 10-Analog Channel, Adaptively Biased Read-Out Front-End IC With Low Intrinsic Timing Resolution for Single-Photon Time-of-Flight PET Applications With Time-Dependent Noise Analysis in 90 nm CMOS.

This paper presents a 10-channel time-of-flight application-specific integrated circuit (ASIC) for positron emission tomography in a 90 nm standard CMOS process. To overcome variations in channel-to-channel timing resolution caused by mismatch and process variations, adaptive biases and a digital-to-analog converter (DAC) are utilized. The main contributions of this work are as follows. First, multistage architectures reduce the total power consumption, and detection bandwidths of analog preamplifiers and comparators are increased to 1 and 1.5 GHz, respectively, relative to those in previous studies. Second, a total intrinsic electronic timing resolution of 9.71 ps root-mean-square (RMS) is achieved (13.88 ps peak and 11.8 ps average of the 10 channels in 5 ASICs). Third, the proposed architecture reduces variations in channel-to-channel timing resolution to 2.6 bits (equivalent to 4.17 ps RMS) by calibrating analog comparator threshold levels. A 181.5 ps full-width-at-half-maximum timing resolution is measured with an avalanche photo diode and a laser setup. The power consumption is 2.5 mW using 0.5 and 1.2 V power supplies. The proposed ASIC is implemented in a 90 nm TSMC CMOS process with a total area of 3.3 mm × 2.7 mm.

[Impact of sperm DNA and acrosome integrity and acrosome reaction rate on outcomes of rescue intracytoplasmic sperm injection].

UNLABELLED: Objective To explore the effects of sperm DNA integrity rate, acrosome integrity rate and acrosome reaction rate on the outcomes of rescue intracytoplasmic sperm injection (ICSI). METHODS: This retrospective analysis was conducted among 97 infertile couples receiving rescue ICSI due to failure of in vitro fertilization procedures in our Reproductive Medicine Center. Of these 97 women, 41 had clinical pregnancy and 56 did not, and the effects of sperm DNA integrity rate (estimated by DNA fragmentation index, DFI), acrosome integrity rate and acrosome reaction rate on rescue ICSI outcomes were analyzed. RESULTS: No significant difference was found in paternal age, testosterone value, testicular volume, FSH, female patient' age or the number of eggs retrieved between the two groups (P>0.05), but the infertility years was significantly shorter in the pregnancy group than in the non-pregnancy group (P<0.05). The fertilization rate and cleavage rate were similar between the two groups (P>0.05), but the good embryo rate was significantly higher in the pregnancy group (P<0.05). The sperm DNA integrity or acrosome reaction rate did not differ significantly between the two groups (P>0.05), but the acrosome integrity rate was significantly higher in the pregnancy group (P<0.05). The sperm DNA integrity rate, acrosome integrity or acrosome reaction rate were not correlated with the fertilization rate, cleavage rate or good embryo rate (P>0.05). The pregnancy rate, twin and single fetus rates were 42.3%, 10.3% and 32.0% in this cohort after recue ICSI, respectively. CONCLUSION: Rescue ICSI is an effective treatment after failed in vitro fertilization procedure, and sperm acrosome integrity rate is associated with the outcome of rescue ICSI.