Fiber-based high-speed 3D schlieren imaging.

This Letter reports the first demonstration of a high-speed three-dimensional (3D) schlieren technique based on the combination of fiber imaging, Toepler's lens-type schlieren, and computed tomography (CT). The technique uses a single high-speed camera, two xenon lamps, and a series of fiber bundles to simultaneously capture the schlieren images of turbulent flames from seven orientations with a framerate beyond tens of kHz. The presented method complements the existing technique with advantages of being flexible, high speed, and low cost. The 3D schlieren technique is first demonstrated and validated on the turbulent premixed flame and stable laminar premixed flame, respectively. Then, the 3D schlieren technique is used to measure the transient, dynamic ignition process. The results show that time-resolved 3D fundamental properties of ignition kernels (i.e., structure and edge speed) can be obtained by the technique.

MicroRNA-based therapy for glioblastoma: Opportunities and challenges.

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor and is characterized by high mortality and morbidity rates and unpredictable clinical behavior. The disappointing prognosis for patients with GBM even after surgery and postoperative radiation and chemotherapy has fueled the search for specific targets to provide new insights into the development of modern therapies. MicroRNAs (miRNAs/miRs) act as oncomirs and tumor suppressors to posttranscriptionally regulate the expression of various genes and silence many target genes involved in cell proliferation, the cell cycle, apoptosis, invasion, stem cell behavior, angiogenesis, the microenvironment and chemo- and radiotherapy resistance, which makes them attractive candidates as prognostic biomarkers and therapeutic targets or agents to advance GBM therapeutics. However, one of the major challenges of successful miRNA-based therapy is the need for an effective and safe system to deliver therapeutic compounds to specific tumor cells or tissues in vivo, particularly systems that can cross the blood-brain barrier (BBB). This challenge has shifted gradually as progress has been achieved in identifying novel tumor-related miRNAs and their targets, as well as the development of nanoparticles (NPs) as new carriers to deliver therapeutic compounds. Here, we provide an up-to-date summary (in recent 5 years) of the current knowledge of GBM-related oncomirs, tumor suppressors and microenvironmental miRNAs, with a focus on their potential applications as prognostic biomarkers and therapeutic targets, as well as recent advances in the development of carriers for nontoxic miRNA-based therapy delivery systems and how they can be adapted for therapy.

Roles of α­synuclein in gastrointestinal microbiome dysbiosis­related Parkinson's disease progression (Review).

Parkinson's disease (PD) is the second most common neurodegenerative disease amongst the middle­aged and elderly populations. Several studies have confirmed that the microbiota­gut­brain axis (MGBA) serves a key role in the pathogenesis of PD. Changes to the gastrointestinal microbiome (GM) cause misfolding and abnormal aggregation of α­synuclein (α­syn) in the intestine. Abnormal α­syn is not eliminated via physiological mechanisms and is transported into the central nervous system (CNS) via the vagus nerve. The abnormal levels of α­syn aggregate in the substantia nigra pars compacta, not only leading to the formation of eosinophilic Lewis Bodies in the cytoplasm and mitochondrial dysfunction in dopaminergic (DA) neurons, but also leading to the stimulation of an inflammatory response in the microglia. These pathological changes result in an increase in oxidative stress (OS), which triggers nerve cell apoptosis, a characteristic of PD. This increase in OS further oxidizes and intensifies abnormal aggregation of α­syn, eventually forming a positive feedback loop. The present review discusses the abnormal accumulation of α­syn in the intestine caused by the GM changes and the increased levels of α­syn transport to the CNS via the MGBA, resulting in the loss of DA neurons and an increase in the inflammatory response of microglial cells in the brain of patients with PD. In addition, relevant clinical therapeutic strategies for improving the GM and reducing α­syn accumulation to relieve the symptoms and progression of PD are described.

TNIP1-mediated TNF-α/NF-κB signalling cascade sustains glioma cell proliferation.

As a malignant tumour of the central nervous system, glioma exhibits high incidence and poor prognosis. Although TNIP1 and the TNF-α/NF-κB axis play key roles in immune diseases and inflammatory responses, their relationship and role in glioma remain unknown. Here, we revealed high levels of TNIP1 and TNF-α/NF-κB in glioma tissue. Glioma cell proliferation was activated with TNF-α treatment and showed extreme sensitivity to the TNF receptor antagonist. Furthermore, loss of TNIP1 disbanded the A20 complex responsible for IκB degradation and NF-κB nucleus translocation, and consequently erased TNFα-induced glioma cell proliferation. Thus, our investigation uncovered a vital function of the TNIP1-mediated TNF-α/NF-κB axis in glioma cell proliferation and provides novel insight into glioma pathology and diagnosis.

3D tomography reconstruction improved by integrating view registration.

Tomographic measurements involve two steps: view registration (VR) to determine the orientation of the projections and the subsequent tomography reconstruction. Therefore, the practical error in both steps impacts the overall accuracy of the final tomographic measurements. Past work treated these two steps separately. This work shows that the overall tomography accuracy can be enhanced substantially if these two steps are considered holistically because there is an opportunity for each step to leverage the information in the other step to improve the overall accuracy if they are considered holistically. Based on this recognition, this work has developed a new method called the reconstruction integration view registration (RIVR) method to implement such a holistic scheme. The key of this implementation involved the use of the Metropolis criterion to adjust the initial orientation provided by the traditional VR process dynamically. Both controlled experiments and accompanying numerical analyses were conducted to validate the RIVR method. Two sets of controlled experiments were conducted and analyzed, including a static uniform dye solution and turbulent flows, where the RIVR technique was demonstrated to significantly reduce the overall reconstruction error (by ∼37% and ∼35%, respectively) compared to past methods that treated VR and tomography separately.

Downregulation of cyclooxygenase­1 stimulates mitochondrial apoptosis through the NF­κB signaling pathway in colorectal cancer cells.

The prognosis of patients with colorectal cancer (CRC) remains poor owing to diagnosis typically occurring at advanced stages of the disease. The understanding of the molecular regulatory signatures of CRC may lead to the identification of biomarkers for the early detection, prevention and clinical intervention of CRC. Epidemiological studies have indicated that cyclooxygenase­1 (COX­1) serves an active function in colon carcinogenesis. However, the molecular mechanism underlying COX­1 regulation in CRC remains unknown. In the present study, COX­1 was identified to be markedly upregulated in colorectal tissues of patients with CRC, and in the CRC cell lines HCT116 and HT29. To determine the function of COX­1 in cancer development, short hairpin RNA knockdown of COX­1 was employed in HCT116 and HT29 CRC cells in the present study. The results demonstrated that silencing of COX­1 depolarized the mitochondrial membrane potential, inhibited adenosine triphosphate production, induced the generation of intracellular reactive oxygen species and triggered caspase­dependent mitochondrial apoptosis. Furthermore, depletion of COX­1 suppressed anti­apoptotic B­cell lymphoma 2 and enhanced pro­apoptotic Bcl­2­associated X protein expression by inhibiting the p65 subunit phosphorylation of nuclear factor κB (NF­κB). Taken together, the results of the present study indicated that COX­1 inhibition significantly triggered cell death by destroying the mitochondrial function that is associated with deactivation of the NF­κB signaling pathway. These results suggest COX­1 as a potential anticancer target in CRC.

Direct comparison of two-dimensional and three-dimensional laser-induced fluorescence measurements on highly turbulent flames.

This Letter reports the first direct comparison between two-dimensional (2D) and three-dimensional (3D) laser-induced fluorescence (LIF) applied to highly turbulent flames, with the goal of experimentally illustrating the capabilities and limitations of volumetric LIF (VLIF). To accomplish these goals, planar LIF (PLIF) and VLIF measurements were simultaneously performed on turbulent flames based on the CH radical. The PLIF measurements imaged a planar cross-section of the target flames across a 2D field-of-view (FOV) of 42 mm×42 mm. The VLIF measurements imaged the same region in the target flame with a 3D FOV of 42 mm×42 mm×5 mm, with 5 mm being the thickness of the measurement volume. The VLIF signals generated in this volume were captured by five intensified cameras from different perspectives, based on which a 3D tomographic reconstruction was performed to obtain the 3D reconstruction of the CH radical (as a marker of the flame front). The PLIF measurements were then compared to a cross-section of the VLIF measurement to demonstrate the feasibility and accuracy of instantaneous 3D imaging of flame topography and flame surface area in highly turbulent flames.

Development and validation of a reconstruction algorithm for three-dimensional nonlinear tomography problems.

This work reports the development and experimental validation of a reconstruction algorithm for three-dimensional (3D) nonlinear tomography problems. Many optical tomography problems encountered in practice are nonlinear, for example, due to significant absorption, multiple-scattering, or radiation trapping. Past research efforts have predominately focused on reconstruction algorithms for linear problems, and these algorithms are not readily extendable to nonlinear problems due to several challenges. These challenges include the computational cost caused by the nonlinearity (which was compounded by the large scale of the problems when they are 3D), the limited view angles available in many practical applications, and the measurement uncertainty. A new algorithm was therefore developed to overcome these challenges. The algorithm was validated both numerically and experimentally, and was demonstrated to be able to solve a range of nonlinear tomography problems with significantly enhanced efficiency and accuracy compared to existing algorithms.

Single-shot volumetric laser induced fluorescence (VLIF) measurements in turbulent flows seeded with iodine.

This work reports the experimental demonstration of single-shot visualization of turbulent flows in all three spatial dimensions (3D) based on volumetric laser induced fluorescence (VLIF). The measurements were performed based on the LIF signal of iodine (I2) vapor seeded in the flow. In contrast to established planar LIF (PLIF) technique, the VLIF technique excited the seeded I2 vapor volumetrically by a thick laser slab. The volumetric LIF signals emitted were then simultaneously collected by a total of five cameras from five different orientations, based on which a 3D tomographic reconstruction was performed to obtain the 3D distribution of the I2 vapor in the target flow. Single-shot measurements (with a measurement duration of a few ns) were demonstrated in a 50 mm × 50 mm × 50 mm volume with a nominal spatial resolution of 0.42 mm and an actual resolution of ~0.71 mm in all three dimensions (corresponding to a total of 120 × 120 × 120 voxels).

Experimental demonstration of 4D imaging in two-phase flows based on computed tomography at 5 kHz.

Turbulent flows inherently feature 3D spatial structures and temporal dynamics. As a result, 4D experimental techniques have been long desired to fully resolve turbulent flows in all three spatial directions and time. This work describes the demonstration of such 4D measurements in two-phase flows using computed tomography and Mie scattering. Demonstration measurements were performed in airflows seeded with water droplets at a 5 kHz frame rate, with an exposure time of 0.2 ms and a measurement volume of 85 mm×85 mm×85 mm discretized into 128×128×128 voxels. Experimental and computational studies have been conducted, with a focus on comparison and validation of the 3D reconstructions against experiments performed in flows with recognizable patterns.

Characterization of linearity and uniformity of fiber-based endoscopes for 3D combustion measurements.

This work reports the application of fiber-based endoscopes (FBEs) for instantaneous three-dimensional (3D) flow and combustion measurements, with an emphasis on characterizing the linearity and uniformity of the FBEs and exploring their potential for obtaining quantitative measurements. Controlled experiments were performed using a uniform illuminator to characterize the linearity and uniformity of the FBEs. Based on such characterization, 3D instantaneous measurements of flames were demonstrated by a combined use of FBEs and tomography. To obtain 3D flame measurement, 3D tomographic reconstructions were made from multiple projections of the target flames collected from various orientations by the FBEs. The results illustrate the potential of FBEs to obtain quantitative 3D flow and combustion measurements and also the advantages FBEs offer, including overcoming optical access restrictions and equipment cost.

Analysis of four-dimensional Mie imaging using fiber-based endoscopes.

This work reports the demonstration and analysis of four-dimensional (4D) imaging measurements in two-phase flows using fiber-based endoscopes (FBEs). Such 4D measurements resolve the droplet distribution in two-phase flows in all three spatial directions and with a temporal resolution of up to 5 kHz. Demonstration measurements were performed in a measurement volume of 85 mm × 85 mm × 85 mm discretized into 64 × 64 × 64 voxels to illustrate FBEs' potential for facilitating practical implementation of 4D tomographic measurements. Mathematical analyses were performed to quantify the fundamental advantage of FBEs to enhance the reconstruction fidelity.