Role of microbiota-gut-brain axis in natural aging-related alterations in behavior.

Introduction: Aging is a complex, time-dependent biological process that involves a decline of overall function. Over the past decade, the field of intestinal microbiota associated with aging has received considerable attention. However, there is limited information surrounding microbiota-gut-brain axis (MGBA) to further reveal the mechanism of aging. Methods: In this study, locomotory function and sensory function were evaluated through a series of behavioral tests.Metabolic profiling were determined by using indirect calorimetry.16s rRNA sequence and targeted metabolomics analyses were performed to investigate alterations in the gut microbiota and fecal short-chain fatty acids (SCFAs). The serum cytokines were detected by a multiplex cytokine assay.The expression of proinflammatory factors were detected by western blotting. Results: Decreased locomotor activity, decreased pain sensitivity, and reduced respiratory metabolic profiling were observed in aged mice. High-throughput sequencing revealed that the levels of genus Lactobacillus and Dubosiella were reduced, and the levels of genus Alistipes and Bacteroides were increased in aged mice. Certain bacterial genus were directly associated with the decline of physiological behaviors in aged mice. Furthermore, the amount of fecal SCFAs in aged mice was decreased, accompanied by an upregulation in the circulating pro-inflammatory cytokines and increased expression of inflammatory factors in the brain. Discussion: Aging-induced microbial dysbiosis was closely related with the overall decline in behavior, which may attribute to the changes in metabolic products, e.g., SCFAs, caused by an alteration in the gut microbiota, leading to inflammaging and contributing to neurological deficits. Investigating the MGBA might provide a novel viewpoint to exploring the pathogenesis of aging and expanding appropriate therapeutic targets.

Nicotinamide Riboside Regulates Chemotaxis to Decrease Inflammation and Ameliorate Functional Recovery Following Spinal Cord Injury in Mice.

Changes in intracellular nicotinamide adenine dinucleotide (NAD+) levels have been observed in various disease states. A decrease in NAD+ levels has been noted following spinal cord injury (SCI). Nicotinamide riboside (NR) serves as the precursor of NAD+. Previous research has demonstrated the anti-inflammatory and apoptosis-reducing effects of NR supplements. However, it remains unclear whether NR exerts a similar role in mice after SCI. The objective of this study was to investigate the impact of NR on these changes in a mouse model of SCI. Four groups were considered: (1) non-SCI without NR (Sham), (2) non-SCI with NR (Sham +NR), (3) SCI without NR (SCI), and (4) SCI with NR (SCI + NR). Female C57BL/6J mice aged 6-8 weeks were intraperitoneally administered with 500 mg/kg/day NR for a duration of one week. The supplementation of NR resulted in a significant elevation of NAD+ levels in the spinal cord tissue of mice after SCI. In comparison to the SCI group, NR supplementation exhibited regulatory effects on the chemotaxis/recruitment of leukocytes, leading to reduced levels of inflammatory factors such as IL-1ß, TNF-α, and IL-22 in the injured area. Moreover, NR supplementation notably enhanced the survival of neurons and synapses within the injured area, ultimately resulting in improved motor functions after SCI. Therefore, our research findings demonstrated that NR supplementation had inhibitory effects on leukocyte chemotaxis, anti-inflammatory effects, and could significantly improve the immune micro-environment after SCI, thereby promoting neuronal survival and ultimately enhancing the recovery of motor functions after SCI. NR supplementation showed promise as a potential clinical treatment strategy for SCI.

Enhancement of Stopping Power Ratio (SPR) Estimation Accuracy through Image-Domain Dual-Energy Computer Tomography for Pencil Beam Scanning System: A Simulation Study.

Our study aims to quantify the impact of spectral separation on achieved theoretical prediction accuracy of proton-stopping power when the volume discrepancy between calibration phantom and scanned object is observed. Such discrepancy can be commonly seen in our CSI pediatric patients. One of the representative image-domain DECT models is employed on a virtual phantom to derive electron density and effective atomic number for a total of 34 ICRU standard human tissues. The spectral pairs used in this study are 90 kVp/140 kVp, without and with 0.1 mm to 0.5 mm additional tin filter. The two DECT images are reconstructed via a conventional filtered back projection algorithm (FBP) on simulated noiseless projection data. The best-predicted accuracy occurs at a spectral pair of 90 kVp/140 kVp with a 0.3 mm tin filter, and the root-mean-squared average error is 0.12% for tissue substitutes. The results reveal that the selected image-domain model is sensitive to spectral pair deviation when there is a discrepancy between calibration and scanning conditions. This study suggests that an optimization process may be needed for clinically available DECT scanners to yield the best proton-stopping power estimation.

MMP1 Overexpression Promotes Cancer Progression and Associates with Poor Outcome in Head and Neck Carcinoma.

Matrix metalloproteinase-1 (MMP1) has been reported to play key roles in a variety of cancers by degrading the extracellular matrix. However, its carcinogenic roles have not been shown yet in head and neck squamous cell carcinoma (HNSCC). This study aimed to elucidate its expression pattern and functional roles as well as clinical significance in HNSCC. The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and immunohistochemistry (IHC) were utilized to determine the MMP1 expression pattern and the associations between its expression and patients' outcome in HNSCC. Mice tongue squamous cell carcinoma model induced by 4-nitroquinoline 1-oxide (4NQO) and siRNA-mediated cellular assay in vitro were utilized to evaluate the oncogenic role of MMP1. The biological functions and cancer-related pathways involved in MMP1-related genes were found through bioinformatics analysis. Both mRNA and protein abundance of MMP1 were highly increased in HNSCC as compared to its non-tumor counterparts. MMP1 overexpression positively correlated with advanced tumor size, cervical node metastasis, and advanced pathological grade and lower patients' survival. In the 4NQO-induced animal model, MMP1 expression increased along with the progression of the disease. In HNSCC cells, siRNA-mediated knockdown of MMP1 significantly inhibited cell proliferation, migration, and invasion and activated apoptosis and epithelia-mesenchymal transition (EMT). GSEA, GO, and KEGG analyses showed that MMP1 expression was significantly related to cancer-related pathways and cancer-related functions. Together, our results demonstrated MMP1 serves as a novel prognostic biomarker and putative oncogene in HNSCC.

Long non-coding RNA LINC01296 promotes progression of oral squamous cell carcinoma through activating the MAPK/ERK signaling pathway via the miR-485-5p/PAK4 axis.

Introduction: Long intergenic non-protein-coding RNA 1296 (LINC01296), a newly identified lncRNA, can function as an oncogenic driver to promote the development of multiple carcinomas. However, the effect of LINC01296 on oral squamous cell carcinoma (OSCC) is still unclear. Material and methods: We determined the expression and role of LINC01296 in OSCC tissues and cell lines. The cell viability, migration and invasion were determined by MTT, wound healing assay and transwell assay, respectively. Flow cytometry was used for detecting cell cycle and apoptosis. The interaction and association between LINC01296, microRNA-485-5p (miR-485-5p) and p21 (RAC1) activated kinase 4 (PAK4) were analyzed by RNA immunoprecipitation (RIP) and luciferase reporter assays. The xenograft mouse model was established to detect the effect of LINC01296 on OSCC tumor growth. Results: Our study showed that LINC01296 was over-expressed in OSCC tissues and cell lines. The level of LINC01296 was positively correlated with the patient's tumor node metastasis (TNM) stage and nodal invasion. Knockdown of LINC01296 effectively inhibits cell viability, migration and invasion but promotes cell apoptosis in vitro. The in vivo experiment showed that LINC01296 knockdown inhibited OSCC tumor growth. The following analysis indicated that LINC01296 acted as a ceRNA for miR-485-5p, and PAK4 was identified as a direct target of miR-485-5p. Furthermore, we found that the effects of LINC01296 on OSCC progression were through regulating the expression of PAK4/p-MEK/p-ERK via sponging miR-485-5p. Conclusions: LINC01296 promote the cell cycle, proliferation, migration and invasion, and inhibit apoptosis of OSCC cells through activating the MAPK/ERK signaling pathway via sponging miR-485-5p to regulate PAK4 expression. These results suggested that the LINC01296/miR-485-5p/PAK4 axis was closely associated with OSCC progression. Our study provides a new insight into the molecular pathogenesis of OSCC, and may supply novel biomarkers for diagnosis and therapy of OSCC.

Structure of Machupo virus polymerase in complex with matrix protein Z.

The Arenaviridae family includes several viruses that cause severe human hemorrhagic fevers with high mortality, with no effective countermeasures currently available. The arenavirus multi-domain L protein is involved in viral transcription and replication and represents a promising target for antiviral drugs. The arenavirus matrix protein Z is a small multi-functional protein that inhibits the activities of the L protein. Here we report the structure of Machupo virus L protein in complex with Z determined by cryo-electron microscopy. The Z protein acts as a staple and binds the L protein with 1:1 stoichiometry at the intersection between the PA-C-like region, RNA-dependent RNA polymerase and PB2-N-like region. Binding of the Z protein may lock the multiple domains of L into a fixed arrangement leading to loss of catalytic activity. These results further our understanding of the inhibitory mechanism of arenavirus replication machinery and provide a novel perspective to develop antiviral drugs.

Characterization and clinical evaluation of microsatellite instability and loss of heterozygosity within tumor-related genes in colorectal cancer.

BACKGROUND: Microsatellite instability (MSI) is a biomarker for better outcomes in colorectal cancer (CRC). However, this conclusion is controversial. In addition, MSs can be a useful marker for loss of heterozygosity (LOH) of genes, but this finding has not been well studied. Here, we aimed to clarify the predictive value of MSI/LOH within tumor-related genes in CRC. METHODS: We detected MSI/LOH of MSs in tumor-related genes and the Bethesda (B5) panel by STR scanning and cloning/sequencing. We further analyzed the relationship between MSI/LOH status and clinical features or outcomes by Pearson's Chi-square test, Fisher's exact test and the Kaplan-Meier method. RESULTS: The findings indicated that the MSI rates of B5 loci were all higher than those of loci in tumor-related genes. Interestingly, MSI/LOH of 2 loci in the B5 panel and 12 loci in tumor-related genes were associated with poorer outcomes, while MSI/LOH of the B5 panel failed to predict outcomes in CRC. MSI of BAT25, MSI/LOH of BAT26 and MSI of the B5 panel showed closer relationships with mucinous carcinoma. In addition, LOH-H of the B5 panel was associated with increased lymphatic metastasis. CONCLUSIONS: In summary, MSI/LOH of certain loci or the whole panel of B5 is related to clinical features, and several loci within tumor-related genes showed prognostic value in the outcomes of CRC.

Design and system evaluation of a dual-panel portable PET (DP-PET).

BACKGROUND: Integrated whole-body PET/MR technology continues to mature and is now extensively used in clinical settings. However, due to the special design architecture, integrated whole-body PET/MR comes with a few inherent limitations. Firstly, whole-body PET/MR lacks sensitivity and resolution for focused organs. Secondly, broader clinical access of integrated PET/MR has been significantly restricted due to its prohibitively high cost. The MR-compatible PET insert is an independent and removable PET scanner which can be placed within an MRI bore. However, the mobility and configurability of all existing MR-compatible PET insert prototypes remain limited. METHODS: An MR-compatible portable PET insert prototype, dual-panel portable PET (DP-PET), has been developed for simultaneous PET/MR imaging. Using SiPM, digital readout electronics, novel carbon fiber shielding, phase-change cooling, and MRI compatible battery power, DP-PET was designed to achieve high-sensitivity and high-resolution with compatibility with a clinical 3-T MRI scanner. A GPU-based reconstruction method with resolution modeling (RM) has been developed for the DP-PET reconstruction. We evaluated the system performance on PET resolution, sensitivity, image quality, and the PET/MR interference. RESULTS: The initial results reveal that the DP-PET prototype worked as expected in the MRI bore and caused minimal compromise to the MRI image quality. The PET performance was measured to show a spatial resolution ≤ 2.5 mm (parallel to the detector panels), maximum sensitivity = 3.6% at the center of FOV, and energy resolution = 12.43%. MR pulsing introduces less than 2% variation to the PET performance measurement results. CONCLUSIONS: We developed a MR-compatible PET insert prototype and performed several studies to begin to characterize the performance of the proposed DP-PET. The results showed that the proposed DP-PET performed well in the MRI bore and would cause little influence on the MRI images. The Derenzo phantom test showed that the proposed reconstruction method could obtain high-quality images using DP-PET.

Characterization and clinical evaluation of microsatellite instability and loss of heterozygosity in tumor-related genes in gastric cancer.

Microsatellite instability (MSI) detection is widely used in the diagnosis and prognosis evaluation of colorectal cancer. However, for gastric cancer (GC), there is no standard panel of microsatellites (MSs) used in clinical guidance. The present study aimed to identify useful predictors of the clinical features and for the prognosis of GC, based on an investigation of MSI and loss of heterozygosity (LOH) in tumor-related genes. First, from 20 tumor-related genes which were proven to be important to the development of GC, 91 MSs were identified, and PCR amplification, short tandem repeat scanning analysis and TA clone sequencing were used to analyze MSI and LOH in the first set of 90 GC samples. Subsequently, the same method was used to detect the MSI/LOH of the optimized loci in the second set of 136 GC samples. MSI/LOH in the mismatch repair genes was highly consistent with that in oncogenes and tumor suppressor genes, respectively. The length of the core sequence was a main factor for the MSI/LOH rate. The MSI of 12 single loci was significantly associated with lymph node metastasis. The MSI in TP53-1 and the LOH in MGMT-10 were significantly associated with early stages of tumor infiltration depth. The LOH in MGMT-10, PTN-2 and MCC-17 was significantly associated with TNM stage. The LOH in TP53-1 and ERBB2-12 was associated with adenocarcinoma. The MSI/LOH in 6 single loci of 5 tumor-related genes was associated with poor prognosis of GC. The present study demonstrated that the MSI/LOH of loci in tumor-associated genes was associated with 4 clinicopathological characteristics and outcomes of GC. These results may provide potential specific biomarkers for the clinical prediction and treatment of GC.

Impact of bowtie filter and detector collimation on multislice CT scatter profiles: A simulation study.

PURPOSE: To investigate via Monte Carlo simulations, the impact of scan subject size, antiscatter grid (ASG), collimator size, and bowtie filter on the distribution of scatter radiation in a typical realistically modeled third generation 16 slice diagnostic computed tomography (CT) scanner. METHODS: Full radiation transport was simulated with Geant4 in a realistic CT scanner geometric model, including the imaging phantom, bowtie filter (BTF), collimators and detector assembly, except for the ASGs. An analytical method was employed to quantify the probable transmission through the ASG of each photon intersecting the detector array. Normalized scatter profiles (NSP) and scatter-to-primary-ratio (SPR) profiles were simulated for 90 and 140 kVp beams for different size phantoms and slice thicknesses. The impact of CT scatter on the reconstructed attenuation coefficient factor was also studied as were the modulating effects of phantom- and patient-tissue heterogeneities on scatter profiles. A method to characterize the relative spatial frequency content of sinogram signals was developed to assess the latter. RESULTS: For the 21.4-cm diameter phantom, NSP and SPR increase linearly with collimator opening for both tube potentials, with the 90 kVp scan exhibiting slightly larger NSP and SPR. The BTF modestly modulates scatter under the phantom center, reducing the prominent off-axis lobes by factors of 1.1-1.3. The ASG reduces scatter on the central axis NSP threefold, and reduces scatter at the detectors outside the phantom shadow by factors of 25 to 500. For the phantoms with diameters of 27 and 32 cm, the scatter increases roughly three- and fourfold, respectively, demonstrating that scatter monotonically increases with phantom size, despite deployment of the ASG and BTF. In the absence of a scan subject, the ASG reduces the signal profile arising photons scattered by the BTF. Without ASG, the in-air scatter profile is relatively flat compared to the scatter profile when the ASG is present. For both 90 and 140 kVp photon spectra, the calculated attenuation coefficient decreases linearly with increasing collimation size. For both homogeneous and heterogeneous objects, NSPs are dominated by low spatial frequency content compared to the primary signal. However, the SPR, which quantifies the local magnitude of nonlinear detector response and is dominated by the high frequency content of the primary profile, can contribute strongly to high-spatial frequency streaking artifacts near high-density structures in reconstructed image artifacts. CONCLUSION: Public-domain Monte Carlo codes, Geant-4 in particular, is a feasible method for characterizing CT detector response to scattered- and off-focal radiation. Our study demonstrates that the ASG substantially reduces the scatter radiation and reshapes scatter-radiation profiles and affects the accuracy with which the detector array can measure narrow-beam attenuation due its inability to distinguish between true uncollided primary and narrow-angle coherently scattered photons. Hence, incorporating the impact of detector array collimation into the forward-projection signal formation models used by iterative reconstruction algorithms is necessary to use CT for accurately characterizing material properties. While tissue heterogeneities exercise a modest influence on local NPS shape and magnitude, they do not add significant high spatial frequency content.

Protective effect of hydroxychloroquine on rheumatoid arthritis-associated atherosclerosis.

BACKGROUND: Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease. We examined the effect of gut microbiota in a mouse model of RA that develops atherosclerosis. METHODS: We created three groups of K/BxN female mice that were positive for the anti-glucose-6-phosphate isomerase (GPI) antibody: control diet (CD), high fat diet (HFD), and HFD with hydroxychloroquine (HFD + HCQ). Serological tests were used to detect the serum levels of total cholesterol (TCHO), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), anti-GPI antibody titers, and serum cytokines. Atherosclerotic plaque was determined by histological analysis, and gut microbiota were determined by 16sV4 sequencing. RESULTS: Relative to mice given the CD, those receiving the HFD had increased serum levels of LDL-C, TCHO, and TG, decreased serum levels of HDL-C, increased atherosclerotic lesions in the aortic root, and altered gut microbiota. Addition of HCQ to HFD decreased the serum levels of LDL-C, TCHO, and TG, increased serum levels of HDL-C, and decreased the atherosclerotic lesions in the aortic root. Mice receiving HFD + HCQ also had the greatest bacterial diversity among the three experimental groups. Moreover, HCQ treatment significantly increased the abundance of Akkermansia and Parabacteroides, and decreased the abundance of Clostridium sensu stricto cluster 1, and therefore may be responsible for the reduced RA-associated atherosclerosis and dyslipidemia. CONCLUSION: Our mouse model of RA indicated that HFD increased ankle width and aggravated atherosclerosis and dyslipidemia, and that HCQ alleviated the dyslipidemia and atherosclerosis, but had no effect on ankle width.

Spatiotemporal dynamics of suspended particulate matter in the Yellow River Estuary, China during the past two decades based on time-series Landsat and Sentinel-2 data.

Twenty-two years of suspended particulate matter (SPM) concentrations in the Yellow River estuary and adjacent sea, China were derived from 532 Landsat and Sentinel 2A/B satellite images. Optimal SPM retrieval model was selected by comparing five state-of-art models using 79 in-situ datasets and recalibrated to ensure consistency among multiple-sensor-derived SPM concentrations. SPM in the estuary, in South Bohai Bay, and Laizhou Bay exhibited distinct temporal variations. 73% and 52% of the interannual and monthly SPM variations near the river mouth were explained by riverine water and sediment discharge, showing impact of the operation of the Xiaolangdi Reservoir and Water-Sediment Regulation Scheme. Land area accretion and erosion in river delta are associated with SPM variation. Riverine impacts on SPM rapidly declined off-shore because of the rapid deposition of the coarse-grain sediment. Ocean current and wind-wave forces explained high concentrations and intra-annual variations of SPM in the South Bohai Bay and Laizhou Bay.

Hyperinsulinemia impairs functions of circulating endothelial progenitor cells.

AIMS: Circulating endothelial progenitor cells (EPCs) play a key role in maintaining endothelial function. Dysfunction of EPCs is associated with the cardiovascular complication of diabetes. The purpose of this study is to investigate the direct effects of hyperinsulinemia on EPCs and the underlying mechanisms. METHODS: EPCs isolated from healthy adults were cultured with various concentrations of insulin (control group, without insulin; physiological insulin group, 10 nM insulin and hyperinsulinemia group, 100 nM insulin) with or without phosphatidylinositol-3-kinase (PI3-K) inhibitor (LY294002, 5 µM), endothelial nitric oxide synthase (eNOS) inhibitor (L-NG-nitro-arginine methyl ester (L-NAME), 100 µM), sodium nitroprusside (SNP, 25 µM), p38 mitogen-activated protein kinase(MAPK) inhibitor (SB203580, 5 µM) or extracellular signal-regulated kinases (ERK) 1/2 inhibitor (PD98059, 10 µM). Proliferation, tube formation, and apoptosis of EPCs were determined. Expressions of eNOS, PI3-K, protein kinase B (Akt), p38 MAPK, and ERK 1/2 were assessed. RESULTS: Hyperinsulinemia caused a significant decrease in proliferation and tube formation abilities than control group. Hyperinsulinemia increased apoptosis rate of EPCs than control group. Furthermore, hyperinsulinemia downregulated phosphorylation of eNOS, PI3-K and Akt, and upregulated phosphorylation of p38 MAPK and ERK. SNP could restore impaired tube formation induced by hyperinsulinemia. P38 MAPK inhibitor but not ERK inhibitor could decrease apoptosis induced by hyperinsulinemia. CONCLUSION: Hyperinsulinemia impaired EPCs' tube formation ability by downregulation of PI-3K/Akt/eNOS pathway. Hyperinsulinemia induced apoptosis of EPCs via upregulation of p38 MAPK.

Biological Response to Recombinant Human Bone Morphogenetic Protein-2 on Bone-Implant Osseointegration in Ovariectomized Experimental Design.

OBJECTIVE: The aim of this study is to investigate the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone-implant osteointegration in osteoporotic rats. MATERIALS AND METHODS: Thirty-six female Wistar rats were randomly divided into 3 groups: sham-operation (SHAM), ovariectomized (OVX), and ovariectomized with rhBMP-2 (OVX + rhBMP-2). The bone density of right tibia was observed with x-ray and the serum alkaline phosphatase (ALP) activity was measured preovariectomy and postovariectomy using an ALP-kit. In OVX + rhBMP-2 group, rhBMP-2 was embedded in the peri-implant area, while SHAM and OVX groups did not contain rhBMP-2. Four and eight weeks after implantation, the rats were killed and the right tibia with implants was taken by x-ray. Histologic changes were investigated by hematoxylin and eosin staining, scanning electron microscope (SEM), and energy dispersive spectrometer examinations. RESULTS: The serum ALP level was significantly higher in ovariectomized rats compared with that before ovariectomy (P < 0.05), while no difference was found in SHAM rats. At 12 weeks after ovariectomy, radiographic and histologic findings showed significant osteoporotic changes in proximal tibial metaphyses of OVX rats, including reduced cortical bone density and enlargement of bone marrow cavity compared with SHAM ones. The results of implantation verified new bone formation around implants in OVX + rhBMP-2 and SHAM groups, indicating favorable bone healing and osseointegration. No bone resorption was found in OVX + rhBMP-2 group, while some soft tissue was observed in bone-implant interface in SHAM group. In OVX group, there was no effective bone-implant osseointegration and mature bone formed around implants, and some implants were even lost due to chronic inflammation. The percentage of calcium and phosphorous atoms was significantly higher and the percentage of sulfur element was significantly lower in peri-implant area in OVX + rhBMP-2 and SHAM groups than that in OVX group. CONCLUSION: rhBMP-2 could enhance the osseous healing and restore bone-implant osseointegration in osteoporotic rats.

Experimental implementation of a joint statistical image reconstruction method for proton stopping power mapping from dual-energy CT data.

PURPOSE: To experimentally commission a dual-energy CT (DECT) joint statistical image reconstruction (JSIR) method, which is built on a linear basis vector model (BVM) of material characterization, for proton stopping power ratio (SPR) estimation. METHODS: The JSIR-BVM method builds on the relationship between the energy-dependent photon attenuation coefficients and the proton stopping power via a pair of BVM component weights. The two BVM component images are simultaneously reconstructed from the acquired DECT sinograms and then used to predict the electron density and mean excitation energy (I-value), which are required by the Bethe equation for SPR computation. A post-reconstruction image-based DECT method, which utilizes the two separate CT images reconstructed via the scanner's software, was implemented for comparison. The DECT measurement data were acquired on a Philips Brilliance scanner at 90 and 140 kVp for two phantoms of different sizes. Each phantom contains 12 different soft and bony tissue surrogates with known compositions. The SPR estimation results were compared to the reference values computed from the known compositions. The difference of the computed water equivalent path lengths (WEPL) across the phantoms between the two methods was also compared. RESULTS: The overall root-mean-square (RMS) of SPR estimation error of the JSIR-BVM method are 0.33% and 0.37% for the head- and body-sized phantoms, respectively, and all SPR estimates of the test samples are within 0.7% of the reference ground truth. The image-based method achieves overall RMS errors of 2.35% and 2.50% for the head- and body-sized phantoms, respectively. The JSIR-BVM method also reduces the pixel-wise random variation by 4-fold to 6-fold within homogeneous regions compared to the image-based method. The average differences between the JSIR-BVM method and the image-based method are 0.54% and 1.02% for the head- and body-sized phantoms, respectively. CONCLUSION: By taking advantage of an accurate polychromatic CT data model and a model-based DECT statistical reconstruction algorithm, the JSIR-BVM method accounts for both systematic bias and random noise in the acquired DECT measurement data. Therefore, the JSIR-BVM method achieves good accuracy and precision on proton SPR estimation for various tissue surrogates and object sizes. In contrast, the experimentally achievable accuracy of the image-based method may be limited by the uncertainties in the image formation process. The result suggests that the JSIR-BVM method has the potential for more accurate SPR prediction compared to post-reconstruction image-based methods in clinical settings.

Low-dose photon counting CT reconstruction bias reduction with multi-energy alternating minimization algorithm.

Photon counting CT (PCCT) is an x-ray imaging technique that has undergone great development in the past decade. PCCT has the potential to improve dose efficiency and low-dose performance. In this paper, we propose a statistics-based iterative algorithm to perform a direct reconstruction of material-decomposed images. Compared with the conventional sinogram-based decomposition method which has degraded performance in low-dose scenarios, the multi-energy alternating minimization algorithm for photon counting CT (MEAM-PCCT) can generate accurate material-decomposed image with much smaller biases.

Cystatin C Expression is Promoted by VEGFA Blocking, With Inhibitory Effects on Endothelial Cell Angiogenic Functions Including Proliferation, Migration, and Chorioallantoic Membrane Angiogenesis.

Background Vascular development, including vasculogenesis and angiogenesis, is involved in many diseases. Cystatin C ( CST 3) is a commonly used marker of renal dysfunction, and we have previously reported that its expression level is associated with variations in the gerbil circle of Willis. Thus, we hypothesized that CST 3 may affect endothelial function and angiogenic capacity. In the current study, we sought to determine the influence of CST 3 on endothelial function and explore its potential regulatory pathway. Methods and Results We analyzed CST 3 and vascular endothelial growth factor A ( VEGFA) levels in different developmental stages of gerbils using ELISA s and immunofluorescence (to examine the relationship between CST 3 and VEGFA . We used a real-time cell analyzer, cytotoxicity assays, and the chorioallantoic membrane assay to investigate the function of CST 3 in endothelial cells and the chorioallantoic membrane. Additionally, we used Western blotting to explore the downstream targets of CST 3. The expression levels of both CST 3 and VEGFA were at their highest on day 10 of the embryonic stage. CST 3 inhibited endothelial cell proliferation, migration, tube formation, and permeability, as well as vascular development in the chorioallantoic membrane. Blocking of VEGFA dose-dependently increased CST 3 expression in arterial and venous endothelial cells. Furthermore, overexpression and knockdown of CST 3 significantly affected the protein levels of p53 and CAPN10 (calpain 10), suggesting that CST 3 might play a role in vascular development through these proteins. Conclusions CST 3 may be associated with vascular development and angiogenesis, and this effect could be promoted by blocking VEGFA .

Urban Land Use and Land Cover Classification Using Novel Deep Learning Models Based on High Spatial Resolution Satellite Imagery.

Urban land cover and land use mapping plays an important role in urban planning and management. In this paper, novel multi-scale deep learning models, namely ASPP-Unet and ResASPP-Unet are proposed for urban land cover classification based on very high resolution (VHR) satellite imagery. The proposed ASPP-Unet model consists of a contracting path which extracts the high-level features, and an expansive path, which up-samples the features to create a high-resolution output. The atrous spatial pyramid pooling (ASPP) technique is utilized in the bottom layer in order to incorporate multi-scale deep features into a discriminative feature. The ResASPP-Unet model further improves the architecture by replacing each layer with residual unit. The models were trained and tested based on WorldView-2 (WV2) and WorldView-3 (WV3) imageries over the city of Beijing. Model parameters including layer depth and the number of initial feature maps (IFMs) as well as the input image bands were evaluated in terms of their impact on the model performances. It is shown that the ResASPP-Unet model with 11 layers and 64 IFMs based on 8-band WV2 imagery produced the highest classification accuracy (87.1% for WV2 imagery and 84.0% for WV3 imagery). The ASPP-Unet model with the same parameter setting produced slightly lower accuracy, with overall accuracy of 85.2% for WV2 imagery and 83.2% for WV3 imagery. Overall, the proposed models outperformed the state-of-the-art models, e.g., U-Net, convolutional neural network (CNN) and Support Vector Machine (SVM) model over both WV2 and WV3 images, and yielded robust and efficient urban land cover classification results.

Mapping radiation distribution on ground based on the measurement using an unmanned aerial vehicle.

Mapping the radiation distribution on ground during a radiological emergency monitoring, or decontamination mission is an important task. Accurate knowledge of the radioactivity distribution can help radiation workers locate the contamination, which reduces unnecessary radiation exposure to personnel and perhaps to some extent also the exposure to the public. Recently, radiation monitoring systems based on unmanned aerial vehicles (UAV) have been widely studied and employed. However, development of algorithms for mapping the contamination from measured data obtained by the detection system mounted on an UAV is still lacking. In this work, we implemented an advanced statistical reconstruction algorithm for mapping spread and point radiation contamination. The algorithm significantly improves accuracy in the scope and location of radiation contamination.