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Objective: The role of gamma‐aminobutyric acid‐ergic (GABAergic) neuron impairment in Alzheimer's disease (AD), and if and how transplantation of healthy GABAergic neurons can improve AD, remain unknown. Methods: Human‐derived medial ganglionic eminence progenitors (hiMGEs) differentiated from programmed induced neural precursor cells (hiNPCs) were injected into the dentate gyrus region of the hippocampus (HIP). Results: We showed that grafts migrate to the whole brain and form functional synaptic connections in amyloid precursor protein gene/ presenilin‐1 (APP/PS1) chimeric mice. Following transplantation of hiMGEs, behavioral deficits and AD‐related pathology were alleviated and defective neurons were repaired. Notably, exosomes secreted from hiMGEs, which are rich in anti‐inflammatory miRNA, inhibited astrocyte activation invitro and in vivo, and the mechanism was related to regulation of CD4+ Th1 cells mediated tumor necrosis factor (TNF) pathway. Interpretation: Taken together, these findings support the hypothesis that hiMGEs transplantation is an alternative treatment for neuronal loss in AD and demonstrate that exosomes with anti‐inflammatory activity derived from hiMGEs are important factors for graft survival. ANN NEUROL 2024;96:488–507 [ABSTRACT FROM AUTHOR]

Chemoresistance to cisplatin (DDP) therapy is a major obstacle that needs to be overcome in treating lung cancer patients. Xanthatin has been reported to exhibit an antitumor effect on various cancers, but the function of xanthatin in DDP‐resistance lung cancer remains unclear. The study aimed to explore the effect and mechanisms of xanthatin on proliferation, apoptosis, and migration in DDP‐resistance lung cancer cells. In the present study, xanthatin suppresses the expression of glucose transporter 1 (GLUT1), attenuates the pentose phosphate pathway (PPP), and causes ROS accumulation and apoptosis, thereby mitigating the antioxidative capacity in DDP‐resistance cells. Previous studies have shown that GLUT1 is associated with resistance to platinum drugs. We found that GLUT1 was significantly increased in the DDP‐resistant lung cancer cell line compared to the parental cell line, and xanthatin significantly downregulated GLUT1 expression in DDP‐resistant lung cancer cells. Notably, overexpression of GLUT1 significantly reduced the production of ROS and increased cellular NADPH/NADP+ and GSH/GSSG ratios. Thus, these results suggest that xanthatin induces DDP‐resistance lung cancer cells apoptosis through regulation of GLUT1‐mediated ROS accumulation. These findings might provide a possible strategy for the clinical treatment of DDP‐resistant lung cancer. [ABSTRACT FROM AUTHOR]

Ferrous iron (Fe2+) has more potent hydroxyl radical (⋅OH)‐generating ability than other Fenton‐type metal ions, making Fe‐based nanomaterials attractive for chemodynamic therapy (CDT). However, because Fe2+ can be converted by ferritin heavy chain (FHC) to nontoxic ferric form and then sequestered in ferritin, therapeutic outcomes of Fe‐mediated CDT agents are still far from satisfactory. Here we report the synthesis of siRNA‐embedded Fe0 nanoparticles (Fe0‐siRNA NPs) for self‐reinforcing CDT via FHC downregulation. Upon internalization by cancer cells, pH‐responsive Fe0‐siRNA NPs are degraded to release Fe2+ and FHC siRNA in acidic endo/lysosomes with the aid of oxygen (O2). The accompanied O2 depletion causes an intracellular pH decrease, which further promotes the degradation of Fe0‐siRNA NPs. In addition to initiating chemodynamic process, Fe2+‐catalyzed ⋅OH generation facilitates endo/lysosomal escape of siRNA by disrupting the membranes, enabling FHC downregulation‐enhanced CDT. [ABSTRACT FROM AUTHOR]

Minimum distance to a solid wall is a primary parameter in turbulence models and overset grid assembly for computational fluid dynamics. In present work, a parallel advancing front method is proposed based on partitioned unstructured grids for the sake of further efficient wall distance computation. In order to overcome the inherent problem of conventional advancing front method in parallel environment, a novel "advancing twice and rippling once" strategy is developed to compute wall distance efficiently and further recover the accuracy. Significantly, the established framework is of modular nature to be easily extended to overset grid system for complex multi‐body configurations. The performance of the developed techniques is evidenced by comparison with the existing alternative ways in terms of computing efficiency and accuracy. Subsequently, further case studies are performed to examine its capability to deal with complex engineering applications such as a full transportation, a wing‐store configuration, a helicopter and a F‐16 fighter with onboard payloads. Results show that the proposed advancing front methodology is in practice able to solve extremely complex geometries with both convex and concave shapes with high efficiency and robustness. [ABSTRACT FROM AUTHOR]

In vivo H2O2 visualization is crucial for disease diagnosis. Catalytic reaction‐based probes show potential in H2O2 detection, yet their in vivo application remains challenging because catalysts always require a specific pH to function and cellular glutathione (GSH) may suppress signaling by depletion of hydroxyl radicals and oxidized substrates. Here, a microenvironment‐tailored catalytic nanoprobe (MTCN) comprising Fe2+, citric acid (CA), 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) diammonium salt (ABTS), and downconversion nanoparticles in the liposomal cavity as well as a reference dye in the lipid membrane is reported, which utilizes the selective permeability of the liposomal membrane to offer a favorable pH for Fe2+ catalyst with the aid of CA and to avoid GSH‐triggered signal loss by preventing entry of GSH into the cavity. The MTCN displays a large NIR‐II fluorescence (FL) ratio between 1550 and 1080 nm (FL1550Em,808Ex/FL1080Em,980Ex), but a small photoacoustic (PA) ratio between 808 and 1048 nm (PA808/PA1048). Upon exposure of MTCN to H2O2, catalytic conversion of ABTS into its oxidized form ABTS·+ with 808 nm absorption causes a noticeable increment in PA808/PA1048 accompanied by an apparent decrement in FL1550Em,808Ex/FL1080Em,980Ex, enabling bimodal ratiometric imaging of H2O2 in the tumor and lymphatic metastasis. [ABSTRACT FROM AUTHOR]

Level of Evidence: 5 Technical Efficacy Stage: 3 [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) results in progressive impairment of upper and lower motor neurons. Increasing evidence from both in vivo and ex vivo studies suggest that iron accumulation in the motor cortex is a neuropathological hallmark in ALS. An in vivo neuroimaging marker of iron dysregulation in ALS would be useful in disease diagnosis and prognosis. Magnetic resonance imaging (MRI), with its unique capability to generate a variety of soft tissue contrasts, provides opportunities to image iron distribution in the human brain with millimeter to sub‐millimeter anatomical resolution. Conventionally, MRI T1‐weighted, T2‐weighted, and T2*‐weighted images have been used to investigate iron dysregulation in the brain in vivo. Susceptibility weighted imaging has enhanced contrast for para‐magnetic materials that provides superior sensitivity to iron in vivo. Recently, the development of quantitative susceptibility mapping (QSM) has realized the possibility of using quantitative assessments of magnetic susceptibility measures in brain tissues as a surrogate measurement of in vivo brain iron. In this review, we provide an overview of MRI techniques that have been used to investigate iron dysregulation in ALS in vivo. The potential uses, strengths, and limitations of these techniques in clinical trials, disease diagnosis, and prognosis are presented and discussed. We recommend further longitudinal studies with appropriate cohort characterization to validate the efficacy of these techniques. We conclude that quantitative iron assessment using recent advances in MRI including QSM holds great potential to be a sensitive diagnostic and prognostic marker in ALS. The use of multimodal neuroimaging markers in combination with iron imaging may also offer improved sensitivity in ALS diagnosis and prognosis that could make a major contribution to clinical care and treatment trials. Level of Evidence: 2 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

The suppression of motion artefacts from MR images is a challenging task. The purpose of this paper was to develop a standalone novel technique to suppress motion artefacts in MR images using a data‐driven deep learning approach. A simulation framework was developed to generate motion‐corrupted images from motion‐free images using randomly generated motion profiles. An Inception‐ResNet deep learning network architecture was used as the encoder and was augmented with a stack of convolution and upsampling layers to form an encoder‐decoder network. The network was trained on simulated motion‐corrupted images to identify and suppress those artefacts attributable to motion. The network was validated on unseen simulated datasets and real‐world experimental motion‐corrupted in vivo brain datasets. The trained network was able to suppress the motion artefacts in the reconstructed images, and the mean structural similarity (SSIM) increased from 0.9058 to 0.9338. The network was also able to suppress the motion artefacts from the real‐world experimental dataset, and the mean SSIM increased from 0.8671 to 0.9145. The motion correction of the experimental datasets demonstrated the effectiveness of the motion simulation generation process. The proposed method successfully removed motion artefacts and outperformed an iterative entropy minimization method in terms of the SSIM index and normalized root mean squared error, which were 5–10% better for the proposed method. In conclusion, a novel, data‐driven motion correction technique has been developed that can suppress motion artefacts from motion‐corrupted MR images. The proposed technique is a standalone, post‐processing method that does not interfere with data acquisition or reconstruction parameters, thus making it suitable for routine clinical practice. [ABSTRACT FROM AUTHOR]

In this paper, the permitted temperature value of the battery cell and DC‐DC converter is proposed. The flow and temperature field of the lithium‐ion batteries is obtained by the computational fluid dynamic method. Thus, the package structure of the battery pack is optimized based on four influencing factors. The results indicate that (1) setting a new inlet on the wall, I can improve ventilation and the inlet is better located below the waist of the battery pack. (2) Air inlet location close to the fan is easy to generate short air circuit, which leads to DC‐DC converter in poor condition of heat dissipation. (3) Adjusting the size of the air inlet mainly affects the temperature distribution of the cells but has little effect on the temperature of the DC‐DC converter. (4) Regulating the gap size can enhance the cell temperature uniformity. (5) The optimized battery pack structure is obtained, where the maximum cell surface temperature is 297.51 K, and the maximum surface temperature of the DC‐DC converter is 339.93 K. The above results provide an approach to exploring the optimal design method of lithium‐ion batteries for the container storage system with better thermal performance. [ABSTRACT FROM AUTHOR]

Tumor cells exhibit higher glycolysis and rely on abnormal energy metabolism to produce ATP, which is essential for cell proliferation and migration. Abnormal energy metabolism inhibition is considered a promising tumor treatment strategy. Xanthatin is an active sesquiterpene lactone isolated from Xanthium strumarium L. This study evaluated the effect of xanthatin on the energy metabolism of human colon cancer cells. The results showed that xanthatin significantly inhibited the migration and invasion of human HT‐29 and HCT‐116 colon cancer cells. We found that xanthatin effectively reduced the production of ATP and promoted the accumulation of lactate. Xanthatin inhibited glycolysis which may be related to the reduction of glucose transporter 1 (Glut1) and monocarboxylate transporter 4 (MCT4) mRNA and protein levels. Concomitantly, xanthatin promoted complex II activity and oxidative phosphorylation (OXPHOS), resulting in mitochondrial damage and cell death in HT‐29 cells. Furthermore, xanthatin inhibited the phosphorylation of mTOR, the phosphorylation of 4E‐binding protein 1 (4E‐BP1) and c‐myc in HT‐29 cells. Moreover, rapamycin, a mTOR inhibitor, could enhance the cytotoxicity effect in xanthatin treated HT‐29 cells. Additionally, HT‐29 cells transfected with si‐mTOR aggravated xanthatin induced cell viability inhibition. Based on these results, we observed that the effect of xanthatin on energy metabolism may be related to its inhibition of the mTOR signaling pathway. Collectively, this study provides important insights into xanthatin's anticancer effect, which occurs by regulation of the energy metabolism of human colon cancer cells, and suggest that xanthatin has potential as a botanical drug against abnormal tumor energy metabolism. [ABSTRACT FROM AUTHOR]

Head motion is a major source of image artefacts in neuroimaging studies and can lead to degradation of the quantitative accuracy of reconstructed PET images. Simultaneous magnetic resonance‐positron emission tomography (MR‐PET) makes it possible to estimate head motion information from high‐resolution MR images and then correct motion artefacts in PET images. In this article, we introduce a fully automated PET motion correction method, MR‐guided MAF, based on the co‐registration of multicontrast MR images. The performance of the MR‐guided MAF method was evaluated using MR‐PET data acquired from a cohort of ten healthy participants who received a slow infusion of fluorodeoxyglucose ([18‐F]FDG). Compared with conventional methods, MR‐guided PET image reconstruction can reduce head motion introduced artefacts and improve the image sharpness and quantitative accuracy of PET images acquired using simultaneous MR‐PET scanners. The fully automated motion estimation method has been implemented as a publicly available web‐service. [ABSTRACT FROM AUTHOR]

An implementation of Non‐Fourier chirp‐encoding in 3D Gradient Recalled Echo (GRE), susceptibility‐weighted imaging (SWI) and Magnetization Prepared Rapid Gradient Echo (MPRAGE) sequences is presented with compressive sensing reconstruction. 3D GRE and MPRAGE sequences were designed, in which the phase encoding (PE) direction was encoded with spatially selective chirp encoding Radio Frequency (RF) pulses, while the slice and the readout directions were Fourier encoded using gradients. During each excitation along the PE direction, a different spatially‐selective RF excitation pulse was used to encode the PE direction with a complete set of unitary chirp encoding basis. Multichannel compressive sensing reconstruction on the undersampled in vivo data demonstrated that images reconstructed from chirp encoded data were able to preserve the spatial resolution better than the Fourier encoding. The mean Structural Similarity (SSIM) across five subjects at the acceleration factor of 6, for chirp encoded MPRAGE was 0.934 compared to 0.912 for Fourier encoded MPRAGE. The implementation of prospective undersampling demonstrated the feasibility of using chirp encoding in clinical practice for accelerated imaging. The minimum intensity projection of the compressive sensing (CS) reconstructed susceptibility weighted images revealed that chirp encoding is able to delineate small vessels better than the Fourier encoding with the SSIM of 0.960 for chirp encoding compared to the SSIM of 0.949 for the Fourier encoding. Improved performance of chirp encoding for CS reconstruction and SWI, along with the feasibility of implementation makes them a practical candidate for clinical MRI scans. [ABSTRACT FROM AUTHOR]

Simultaneous Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) scanning is a recent major development in biomedical imaging. The full integration of the PET detector ring and electronics within the MR system has been a technologically challenging design to develop but provides capacity for simultaneous imaging and the potential for new diagnostic and research capability. This article reviews state‐of‐the‐art MR‐PET hardware and software, and discusses future developments focusing on neuroimaging methodologies for MR‐PET scanning. We particularly focus on the methodologies that lead to an improved synergy between MRI and PET, including optimal data acquisition, PET attenuation and motion correction, and joint image reconstruction and processing methods based on the underlying complementary and mutual information. We further review the current and potential future applications of simultaneous MR‐PET in both systems neuroscience and clinical neuroimaging research. We demonstrate a simultaneous data acquisition protocol to highlight new applications of MR‐PET neuroimaging research studies. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: The aim of our study was to investigate the immunomodulatory effect and short‐term efficacy and long‐term prognosis of decompensated liver cirrhosis patients caused by hepatitis B after a double transplantation with human umbilical cord mesenchymal stem cells (hUCMSCs). Methods: Fifty inpatients were recruited and given the same medical treatments, receiving hUCMSCs injection intravenously. Fifty‐three patients (Group B) matched for age, sex, and baseline alanine aminotransferase, aspartate aminotransferase, albumin, total bilirubin, prothrombin time, and model for end‐stage liver disease score and Child–Pugh classification, acted as the control group. Results: Interleukin‐6 and tumor necrosis factor alpha levels markedly decreased, and interleukin‐10 level apparently increased in Group A at 2 and 4 weeks after treatment. Transforming growth factor beta in Group A increased more remarkably at 2 weeks after treatment. T4 cells and Treg cells in Group A were apparently higher than those in Group B at 2 and 4 weeks after treatment, and T8 cells and B cells were significantly lower than those in Group B. Aspartate aminotransferase levels in Group A were dramatically declining at 8 and 12 weeks after treatment. Levels of albumin, total bilirubin, and prothrombin time in Group A were apparently improved from 4 to 12 weeks after treatment. The improvements in model for end‐stage liver disease and Child–Pugh scores in Group A were notably superior to those in Group B from 4 to 36 weeks after treatment. There were no remarkable differences in the incidence of developing liver failure throughout the follow‐up period, but the mortality rate of Group A was lower than that of Group B. Conclusion: This therapeutic method may be an appropriate choice for patients with decompensated liver cirrhosis. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-related apoptosis-inducing ligand ( TRAIL) is a member of the tumor necrosis factor superfamily, whose members are capable of inducing apoptosis and inflammation. Endoplasmic reticulum stress ( ERS) plays a key role in immune surveillance in macrophages. TRAIL mRNA and protein expression have previously been detected in macrophages; however, whether ERS has any effects on TRAIL expression in macrophages has not yet been determined. Here, we demonstrate that thapsigargin ( TG) and tunicamycin ( TM), two ERS inducers activated macrophages were able to increase TRAIL mRNA and protein expression in RAW264.7 macrophages, the culture supernatant of THP-1 cells, and mouse peritoneal macrophages, indicating that ERS as a potent inducer of TRAIL transcription and expression in macrophages. This effect was blocked by the specific JNK inhibitor SP600125 and transcription factor AP-1 inhibitor SR 1130. Interestingly, at the molecular level, regulation of TRAIL expression by ERS was accompanied by a significant decrease in cytokine signaling suppressor 3 ( SOCS3). SOCS3 si RNA clearly increased the expression of TRAIL mRNA and protein under ERS by activating the AP-1 components phosphorylated c-Jun and phosphorylated c-Fos in RAW264.7 cells. In contrast, over-expression of SOCS3 reversed ERS-induced TRAIL expression. These findings provide in vitro evidence that SOCS3 plays a critical negative role in the regulation of ERS-induced TRAIL expression via the Jun N-terminal kinase/ AP-1 signaling pathway in macrophages. [ABSTRACT FROM AUTHOR]

microRNAs (miRNAs) are emerging as important gene expression regulators linked to various biological processes at a posttranscriptional level. miRNAs have been known to play important roles in cell proliferation, cell differentiation, and apoptosis. Recently, accumulate studies indicate that up-regulation of miR-155 has been described in several types of human tumors. miR-155 has been considered to act as an oncogene or a tumor suppressor, depending on tumor system. Silencing oncomiRs or gene therapy approaches could be an effective therapeutic approach against tumor. Here we review the current knowledge on the functional role of miR-155 in the control of various cancers. J. Cell. Physiol. 229: 545-550, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Recent advances in high field magnetic resonance technology have increased the interest in the phase of the complex data. Processed phase images are derived from the phase signal by removing the bias field and phase wraps from the initial data. However, the usefulness of this data has been hindered by artifacts at the brain/non-brain surface, particularly in cortical regions. A method is proposed that efficiently removes surface artifacts by performing Gaussian filtering with spatially varying parameters of unwrapped or complex filtered phase images. The proposed method is shown to produce improved images, revealing underlying structure and detail that are otherwise obscured by surface artifacts in images produced by traditional phase processing methods. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Accelerated parallel MRI has advantage in imaging speed, and its image quality has been improved continuously in recent years. This paper introduces a two-dimensional infinite impulse response model of inverse filter to replace the finite impulse response model currently used in generalized autocalibrating partially parallel acquisitions class image reconstruction methods. The infinite impulse response model better characterizes the correlation of k-space data points and better approximates the perfect inversion of parallel imaging process, resulting in a novel generalized image reconstruction method for accelerated parallel MRI. This k-space-based reconstruction method includes the conventional generalized autocalibrating partially parallel acquisitions class methods as special cases and has a new infinite impulse response data estimation mechanism for effective improvement of image quality. The experiments on in vivo MRI data show that the proposed method significantly reduces reconstruction errors compared with the conventional two-dimensional generalized autocalibrating partially parallel acquisitions method, particularly at the high acceleration rates. Magn Reson Med, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Summary: Clusters based on hybrid architectures combining ARM CPUs and FPGA fabric, such as the Xilinx Zynq SoC, not only are energy‐efficient platforms with strong processing power but also have the advantages of distributed computing systems balancing the workload between cores, processors, and nodes. This paper employs a 48‐node cluster infrastructure based on the Xilinx Zynq SoC to accelerate classical cryptographic algorithms, including hash functions, AES, and RSA. In this design, we leverage the flexibility of the software to implement node‐to‐node communication through the message passing interface (MPI), and we offload the compute‐intensive tasks to the FPGA to accelerate complex calculations with the parallelizability of specific reconfigurable coprocessors. In addition, we study several parallel cryptography optimizations based on FPGA to evaluate this cluster. Finally, using a comparison with a multi‐core desktop (Intel i7‐3770) and a many‐core server (288 cores), the efficiency of the implementations of the selected data encryption and decryption algorithms is presented to illustrate the performance of our system; we also gain up to 3.6× increase in energy efficiency. [ABSTRACT FROM AUTHOR]