Publications by authors named "Yong Du"

393 Publications

Microwave Imaging by Deep Learning Network: Feasibility and Training Method.

Authors:
Wenyi Shao Yong Du

IEEE Trans Antennas Propag 2020 Jul 12;68(7):5626-5635. Epub 2020 Mar 12.

Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD 21287 USA.

Microwave image reconstruction based on a deep-learning method is investigated in this paper. The neural network is capable of converting measured microwave signals acquired from a 24×24 antenna array at 4 GHz into a 128×128 image. To reduce the training difficulty, we first developed an autoencoder by which high-resolution images (128×128) were represented with 256×1 vectors; then we developed the second neural network which aimed to map microwave signals to the compressed features (256×1 vector). Two neural networks can be combined to a full network to make reconstructions, when both are successfully developed. The present two-stage training method reduces the difficulty in training deep learning networks (DLN) for inverse reconstruction. The developed neural network is validated by simulation examples and experimental data with objects in different shapes/sizes, placed in different locations, and with dielectric constant ranging from 2~6. Comparisons between the imaging results achieved by the present method and two conventional approaches: distorted Born iterative method (DBIM) and phase confocal method (PCM) are also provided.
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http://dx.doi.org/10.1109/tap.2020.2978952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189033PMC
July 2020

A three-stage, deep learning, ensemble approach for prognosis in patients with Parkinson's disease.

EJNMMI Res 2021 Jun 7;11(1):52. Epub 2021 Jun 7.

The Russell H. Morgan, Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.

Background: Diagnosis of Parkinson's disease (PD) is informed by the presence of progressive motor and non-motor symptoms and by imaging dopamine transporter with [I]ioflupane (DaTscan). Deep learning and ensemble methods have recently shown promise in medical image analysis. Therefore, this study aimed to develop a three-stage, deep learning, ensemble approach for prognosis in patients with PD.

Methods: Retrospective data of 198 patients with PD were retrieved from the Parkinson's Progression Markers Initiative database and randomly partitioned into the training, validation, and test sets with 118, 40, and 40 patients, respectively. The first and second stages of the approach extracted features from DaTscan and clinical measures of motor symptoms, respectively. The third stage trained an ensemble of deep neural networks on different subsets of the extracted features to predict patient outcome 4 years after initial baseline screening. The approach was evaluated by assessing mean absolute percentage error (MAPE), mean absolute error (MAE), Pearson's correlation coefficient, and bias between the predicted and observed motor outcome scores. The approach was compared to individual networks given different data subsets as inputs.

Results: The ensemble approach yielded a MAPE of 18.36%, MAE of 4.70, a Pearson's correlation coefficient of 0.84, and had no significant bias indicating accurate outcome prediction. The approach outperformed individual networks not given DaTscan imaging or clinical measures of motor symptoms as inputs, respectively.

Conclusion: The approach showed promise for longitudinal prognostication in PD and demonstrated the synergy of imaging and non-imaging information for the prediction task.
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http://dx.doi.org/10.1186/s13550-021-00795-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184905PMC
June 2021

Strain Modulation of Selectively and/or Globally Grown Ge Layers.

Nanomaterials (Basel) 2021 May 28;11(6). Epub 2021 May 28.

Key laboratory of Microelectronic Devices & Integrated Technology, Institute of Microelectronics, Chinese Academy of Sciences, Beijing 100029, China.

This article presents a novel method to grow a high-quality compressive-strain Ge epilayer on Si using the selective epitaxial growth (SEG) applying the RPCVD technique. The procedures are composed of a global growth of Ge layer on Si followed by a planarization using CMP as initial process steps. The growth parameters of the Ge layer were carefully optimized and after cycle-annealing treatments, the threading dislocation density (TDD) was reduced to 3 × 10 cm. As a result of this process, a tensile strain of 0.25% was induced, whereas the RMS value was as low as 0.81 nm. Later, these substrates were covered by an oxide layer and patterned to create trenches for selective epitaxy growth (SEG) of the Ge layer. In these structures, a type of compressive strain was formed in the SEG Ge top layer. The strain amount was -0.34%; meanwhile, the TDD and RMS surface roughness were 2 × 10 cm and 0.68 nm, respectively. HRXRD and TEM results also verified the existence of compressive strain in selectively grown Ge layer. In contrast to the tensile strained Ge layer (globally grown), enhanced PL intensity by a factor of more than 2 is partially due to the improved material quality. The significantly high PL intensity is attributed to the improved crystalline quality of the selectively grown Ge layer. The change in direct bandgap energy of PL was observed, owing to the compressive strain introduced. Hall measurement shows that a selectively grown Ge layer possesses room temperature hole mobility up to 375 cm/Vs, which is approximately 3 times larger than that of the Ge (132 cm/Vs). Our work offers fundamental guidance for the growth of high-quality and compressive strain Ge epilayer on Si for future Ge-based optoelectronics integration applications.
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http://dx.doi.org/10.3390/nano11061421DOI Listing
May 2021

Social capital and cognitive decline: Does sleep duration mediate the association?

PLoS One 2021 27;16(5):e0252208. Epub 2021 May 27.

Key Laboratory of the Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, China.

Background: Studies have found that social capital (SC) is associated with the risk of cognitive decline; however, the mechanism explaining how SC leads to cognitive decline is unclear. The current study examines the mediation effect of sleep duration on the relationship between SC and cognitive decline in Chinese older adults.

Methods: A cross-sectional study of 955 community-dwelling aged 60 or over was conducted. The mini-mental state examination (MMSE), self-report sleep duration questionnaire, and social capital scales were administered during the face-to-face survey. The Bootstrap methods PROCESS program is employed to test the mediation model.

Results: After controlling for covariates, both social cohesion and social interaction were positively correlated with the MMSE score (p<0.001), and social cohesion was negatively correlated with sleep duration (p = 0.009); On the contrary, sleep duration was negatively correlated with MMSE score (p<0.001). Linear regression analysis showed social cohesion was positively associated with the MMSE score (β = 0.16, p = 0.005), while sleep duration was associated with an increased risk of cognitive decline (β = -0.72, p<0.001). Sleep duration has mediated the relationship between social cohesion and cognitive decline (explaining 21.7% of the total variance).

Conclusions: Social capital negatively associated with the risk of cognitive decline in this Chinese population, and sleep duration may partly explain this relationship. It may be a suggestive clue to identify those at a higher risk of progressing to cognitive impairment. Further prospective study in need to confirm this finding due to the cross-sectional design.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252208PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158899PMC
May 2021

Identification of poly(ADP-ribose) polymerase 9 (PARP9) as a noncanonical sensor for RNA virus in dendritic cells.

Nat Commun 2021 05 11;12(1):2681. Epub 2021 May 11.

Department of Surgery and Immunobiology and Transplant Science Center, Houston Methodist, Houston, TX, USA.

Innate immune cells are critical in protective immunity against viral infections, involved in sensing foreign viral nucleic acids. Here we report that the poly(ADP-ribose) polymerase 9 (PARP9), a member of PARP family, serves as a non-canonical sensor for RNA virus to initiate and amplify type I interferon (IFN) production. We find knockdown or deletion of PARP9 in human or mouse dendritic cells and macrophages inhibits type I IFN production in response to double strand RNA stimulation or RNA virus infection. Furthermore, mice deficient for PARP9 show enhanced susceptibility to infections with RNA viruses because of the impaired type I IFN production. Mechanistically, we show that PARP9 recognizes and binds viral RNA, with resultant recruitment and activation of the phosphoinositide 3-kinase (PI3K) and AKT3 pathway, independent of mitochondrial antiviral-signaling (MAVS). PI3K/AKT3 then activates the IRF3 and IRF7 by phosphorylating IRF3 at Ser385 and IRF7 at Ser437/438 mediating type I IFN production. Together, we reveal a critical role for PARP9 as a non-canonical RNA sensor that depends on the PI3K/AKT3 pathway to produce type I IFN. These findings may have important clinical implications in controlling viral infections and viral-induced diseases by targeting PARP9.
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http://dx.doi.org/10.1038/s41467-021-23003-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113569PMC
May 2021

Th17/Treg cell imbalance plays an important role in respiratory syncytial virus infection compromising asthma tolerance in mice.

Microb Pathog 2021 Jul 4;156:104867. Epub 2021 May 4.

Department of Pulmonary and Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China; Center of Community-Based Health Research, Fudan University, China. Electronic address:

Mucosal tolerance is induced early in life and is an important mechanism of protection from diseases, such as asthma. Respiratory syncytial virus (RSV) is a main cause of bronchiolitis and pneumonia in infants. Clinical studies have found that there is a strong association between RSV infection in infancy and later development of asthma, but the underlying mechanisms are unclear. A mouse model of immune tolerance induced by oral feeding of ovalbumin(OVA) was successfully established in our previous studies. We found that RSV infection could break the oral immune tolerance state.RSV infection increased the mRNA expression of IL-17A and IL-17A/Foxp3(the transcription factor forkhead box P3) in OT mice, but the mRNA expression of IL-4 and other T helper(Th)2 cytokines did not change significantly. As detected by flow cytometry analysis, RSV infection elevated Th17 cell levels and correspondingly decreased Regulatory T(Treg) cell levels in the hilar lymph nodes (HLNs) and mesenteric lymph nodes (MLNs), but there were no significant differences in the spleen or peripheral blood.We hypothesized that an imbalance in Th cells played an important role in RSV infection compromising asthma tolerance.RSV infection disrupted asthma tolerance by increasing the Th17/Treg ratio rather than the Th1/Th2 ratio'.Therefore, altering the Th17/Treg ratio has been identified as a potential therapeutic target in asthma caused by RSV or another virus.
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http://dx.doi.org/10.1016/j.micpath.2021.104867DOI Listing
July 2021

Hematological characteristics of patients with novel coronavirus pneumonia in intensive care unit.

Int Immunopharmacol 2021 Apr 20;97:107697. Epub 2021 Apr 20.

Department of Pulmonary and Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China. Electronic address:

Background: Toward the end of December 2019, a novel type of coronavirus (2019-nCoV) broke out in Wuhan, China. Here, the hematological characteristics of patients with severe and critical 2019-nCoV pneumonia in intensive care unit (ICU) were investigated, which may provide the necessary basis for its diagnosis and treatment.

Methods: We collected data on patients with confirmed 2019-nCoV pneumonia in the ICU of Leishenshan Hospital in Wuhan from February 25 to April 2, 2020. Real-time reverse-transcription polymerase chain reaction was used to confirm the presence of 2019-nCoV, and various hematological characteristics were analyzed.

Results: All patients tested positive for 2019-nCoV using nasopharyngeal swabs or sputum after admission, and interstitial pneumonia findings were noted on chest computed tomography. Sex, age and comorbidities were not significantly different between the severe and critical groups. In terms of prognosis, the survival rate of patients in the severe group reached 100%, whereas that of patients in the critical group was only 13.33% after positive treatment. Furthermore, lymphocyte percentage, blood urea nitrogen, calcium, D-dimer, myohemoglobin, procalcitonin, and IL-6 levels were high-risk factors for disease progression in critical patients. Finally, lymphocyte percentage and blood urea nitrogen, calcium, myohemoglobin, and IL-6 levels were closely associated with patient prognosis.

Conclusions: 2019-nCoV pneumonia should be considered a systemic disease. Patients with more complications were more likely to develop critical disease. Lymphocyte percentage and blood urea nitrogen, calcium, myohemoglobin, and IL-6 levels can be monitored to prevent progression critical disease.
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http://dx.doi.org/10.1016/j.intimp.2021.107697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057740PMC
April 2021

High Performance p-i-n Photodetectors on Ge-on-Insulator Platform.

Nanomaterials (Basel) 2021 Apr 27;11(5). Epub 2021 Apr 27.

Key Laboratory of Microelectronics Devices & Integrated Technology, Institute of Microelectronics, Chinese Academy of Sciences, Beijing 100029, China.

In this article, we demonstrated novel methods to improve the performance of p-i-n photodetectors (PDs) on a germanium-on-insulator (GOI). For GOI photodetectors with a mesa diameter of 10 μm, the dark current at -1 V is 2.5 nA, which is 2.6-fold lower than that of the Ge PD processed on Si substrates. This improvement in dark current is due to the careful removal of the defected Ge layer, which is formed with the initial growth of Ge on Si. The bulk leakage current density and surface leakage density of the GOI detector at -1 V are as low as 1.79 mA/cm and 0.34 μA/cm, respectively. GOI photodetectors with responsivity of 0.5 and 0.9 A/W at 1550 and 1310 nm wavelength are demonstrated. The optical performance of the GOI photodetector could be remarkably improved by integrating a tetraethylorthosilicate (TEOS) layer on the oxide side due to the better optical confinement and resonant cavity effect. These PDs with high performances and full compatibility with Si CMOS processes are attractive for applications in both telecommunications and monolithic optoelectronics integration on the same chip.
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http://dx.doi.org/10.3390/nano11051125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145456PMC
April 2021

Investigation of the Heteroepitaxial Process Optimization of Ge Layers on Si (001) by RPCVD.

Nanomaterials (Basel) 2021 Apr 6;11(4). Epub 2021 Apr 6.

Key Laboratory of Microelectronic Devices & Integrated Technology, Institute of Microelectronics, Chinese Academy of Sciences, Beijing 100029, China.

This work presents the growth of high-quality Ge epilayers on Si (001) substrates using a reduced pressure chemical vapor deposition (RPCVD) chamber. Based on the initial nucleation, a low temperature high temperature (LT-HT) two-step approach, we systematically investigate the nucleation time and surface topography, influence of a LT-Ge buffer layer thickness, a HT-Ge growth temperature, layer thickness, and high temperature thermal treatment on the morphological and crystalline quality of the Ge epilayers. It is also a unique study in the initial growth of Ge epitaxy; the start point of the experiments includes Stranski-Krastanov mode in which the Ge wet layer is initially formed and later the growth is developed to form nuclides. Afterwards, a two-dimensional Ge layer is formed from the coalescing of the nuclides. The evolution of the strain from the beginning stage of the growth up to the full Ge layer has been investigated. Material characterization results show that Ge epilayer with 400 nm LT-Ge buffer layer features at least the root mean square (RMS) value and it's threading dislocation density (TDD) decreases by a factor of 2. In view of the 400 nm LT-Ge buffer layer, the 1000 nm Ge epilayer with HT-Ge growth temperature of 650 °C showed the best material quality, which is conducive to the merging of the crystals into a connected structure eventually forming a continuous and two-dimensional film. After increasing the thickness of Ge layer from 900 nm to 2000 nm, Ge surface roughness decreased first and then increased slowly (the RMS value for 1400 nm Ge layer was 0.81 nm). Finally, a high-temperature annealing process was carried out and high-quality Ge layer was obtained (TDD=2.78 × 10 cm). In addition, room temperature strong photoluminescence (PL) peak intensity and narrow full width at half maximum (11 meV) spectra further confirm the high crystalline quality of the Ge layer manufactured by this optimized process. This work highlights the inducing, increasing, and relaxing of the strain in the Ge buffer and the signature of the defect formation.
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http://dx.doi.org/10.3390/nano11040928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067383PMC
April 2021

Learning fuzzy clustering for SPECT/CT segmentation via convolutional neural networks.

Med Phys 2021 Apr 27. Epub 2021 Apr 27.

Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD, USA.

Purpose: Quantitative bone single-photon emission computed tomography (QBSPECT) has the potential to provide a better quantitative assessment of bone metastasis than planar bone scintigraphy due to its ability to better quantify activity in overlapping structures. An important element of assessing the response of bone metastasis is accurate image segmentation. However, limited by the properties of QBSPECT images, the segmentation of anatomical regions-of-interests (ROIs) still relies heavily on the manual delineation by experts. This work proposes a fast and robust automated segmentation method for partitioning a QBSPECT image into lesion, bone, and background.

Methods: We present a new unsupervised segmentation loss function and its semi- and supervised variants for training a convolutional neural network (ConvNet). The loss functions were developed based on the objective function of the classical Fuzzy C-means (FCM) algorithm. The first proposed loss function can be computed within the input image itself without any ground truth labels, and is thus unsupervised; the proposed supervised loss function follows the traditional paradigm of the deep learning-based segmentation methods and leverages ground truth labels during training. The last loss function is a combination of the first and the second and includes a weighting parameter, which enables semi-supervised segmentation using deep learning neural network.

Experiments And Results: We conducted a comprehensive study to compare our proposed methods with ConvNets trained using supervised, cross-entropy and Dice loss functions, and conventional clustering methods. The Dice similarity coefficient (DSC) and several other metrics were used as figures of merit as applied to the task of delineating lesion and bone in both simulated and clinical SPECT/CT images. We experimentally demonstrated that the proposed methods yielded good segmentation results on a clinical dataset even though the training was done using realistic simulated images. On simulated SPECT/CT, the proposed unsupervised model's accuracy was greater than the conventional clustering methods while reducing computation time by 200-fold. For the clinical QBSPECT/CT, the proposed semi-supervised ConvNet model, trained using simulated images, produced DSCs of and for lesion and bone segmentation in SPECT, and a DSC of bone segmentation of CT images. These DSCs were larger than that for standard segmentation loss functions by for SPECT segmentation, and for CT segmentation with P-values from a paired t-test.

Conclusions: A ConvNet-based image segmentation method that uses novel loss functions was developed and evaluated. The method can operate in unsupervised, semi-supervised, or fully-supervised modes depending on the availability of annotated training data. The results demonstrated that the proposed method provides fast and robust lesion and bone segmentation for QBSPECT/CT. The method can potentially be applied to other medical image segmentation applications.
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http://dx.doi.org/10.1002/mp.14903DOI Listing
April 2021

Parity-Violating Møller Scattering at Next-to-Next-to-Leading Order: Closed Fermion Loops.

Phys Rev Lett 2021 Apr;126(13):131801

Amherst Center for Fundamental Interactions, Physics Department, University of Massachusetts Amherst, Amherst, Massachusetts 01003 USA.

A complete, gauge-invariant computation of two-loop virtual corrections involving closed fermion loops to the polarized Møller scattering asymmetry is presented. The set of contributions involving two closed fermion loops and the set involving one closed fermion loop are numerically similar in magnitude to the one-loop bosonic corrections and yield an overall correction of 1.3% relative to the tree level asymmetry. We estimate sizes of the remaining two-loop contributions and discuss implications for the upcoming MOLLER (Measurement of a Lepton-Lepton Electroweak Reaction) experiment.
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http://dx.doi.org/10.1103/PhysRevLett.126.131801DOI Listing
April 2021

Six-fold increase of atmospheric pCO during the Permian-Triassic mass extinction.

Nat Commun 2021 04 9;12(1):2137. Epub 2021 Apr 9.

Department of Earth and Environmental Studies, Montclair State University, Montclair, NJ, USA.

The Permian-Triassic mass extinction was marked by a massive release of carbon into the ocean-atmosphere system, evidenced by a sharp negative carbon isotope excursion. Large carbon emissions would have increased atmospheric pCO and caused global warming. However, the magnitude of pCO changes during the PTME has not yet been estimated. Here, we present a continuous pCO record across the PTME reconstructed from high-resolution δC of C plants from southwestern China. We show that pCO increased from 426 +133/-96 ppmv in the latest Permian to 2507 +4764/-1193 ppmv at the PTME within about 75 kyr, and that the reconstructed pCO significantly correlates with sea surface temperatures. Mass balance modelling suggests that volcanic CO is probably not the only trigger of the carbon cycle perturbation, and that large quantities of C-depleted carbon emission from organic matter and methane were likely required during complex interactions with the Siberian Traps volcanism.
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http://dx.doi.org/10.1038/s41467-021-22298-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035180PMC
April 2021

Influence of CrC and VC Content on WC Grain Size, WC Shape and Mechanical Properties of WC-6.0 wt. % Co Cemented Carbides.

Materials (Basel) 2021 Mar 22;14(6). Epub 2021 Mar 22.

State Key Laboratory for Powder Metallurgy, Central South University, Changsha 410083, China.

In this paper, the influences of CrC/VC content on WC grain size, WC grain shape and mechanical properties of WC-6 wt. % Co cemented carbides were investigated. The results showed that the grain size first rapidly decreased and then slightly decreased with the increasing CrC/VC content, and VC led to finer grain size and narrower size distribution. HRTEM/EDS analysis of the WC/Co interface indicates that the segregation concentration of V is much larger than that of Cr, which may be a strong response to the higher inhibition efficiency of VC. The addition of CrC induced triangular prism shape WC grains while VC generated stepped triangular prism grains. Despite the grain growth inhibitor (GGI) mechanisms of CrC/VC have been extensively studied in the literature, the doping amount, especially the doping limit, has not been systematically investigated. In this work, the saturated solubilities of Cr and V in cobalt binder phase along with carbon content hare been predicted based on thermodynamic calculations. Based on the theoretical calculations, the doping amount of CrC/VC is designed to be gradually increasing until more or less over their maximum solubilities in the binder phase, thereby investigating the subsequent microstructure and mechanical properties. When the doping of CrC/VC exceeds the maximum solubility in Co phase, Co-rich Cr-carbides and Co-deficient V-carbides would form respectively, which were detrimental to the transverse rupture strength (TRS) and impact toughness. The hardness increased with the increasing CrC/VC content, while the fracture toughness decreased with the increasing CrC/VC content. The TRS initially enhanced and then declined, but the stepped triangular prism shape grains and low fraction of WC/Co interface in WC-6Co-VC cemented carbide led to a more pronounced decline in the TRS. The sample with 0.6 wt. % CrC addition had good comprehensive mechanical properties, its hardness, fracture toughness and TRS were 1880 kg/mm, 9.32 MPa·m and 3450 MPa, respectively.
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http://dx.doi.org/10.3390/ma14061551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004746PMC
March 2021

Altered peri-seizure EEG microstate dynamics in patients with absence epilepsy.

Seizure 2021 May 25;88:15-21. Epub 2021 Mar 25.

Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China; Laboratory of Neurological Diseases and Brain Function, Luzhou, 646000, China. Electronic address:

Objective: To investigate whether the parameters of EEG microstates changed before and after an absence seizure episode.

Methods: AE patients with a current high frequency of seizures were included (n=21). Each included subject underwent a two-hour and 19-channel video EEG examination. Five epochs of 10-second EEG data in interictal, pre-seizure, and post-seizure states were collected from each AE patient. Five 10-second resting-state EEG epochs from sex- and age-matched HCs who reported no history of neurological or psychiatric disorders and visited the hospital for routine physical examinations were collected. Microstate analysis and source localization of microstates were performed using the LORETA KEY tool.

Results: Compared with the resting-state EEGs of HCs, the interictal EEGs of AE patients showed a higher relative transition rate from microstates B to D (p<0.05). From interictal to pre-seizure EEG, the total time ratio of microstate C and the occurrence of microstate B decreased significantly, while the duration of microstate B increased significantly (p<0.05). Compared with pre-seizure EEGs, microstate C in post-seizure EEGs showed a significantly downregulated total time percentage and occurrence (p<0.05). The source localization of each microstate in each condition also varied and showed spatial recovery tends from pre- to post-seizure states.

Conclusion: Altered EEG microstate dynamics exist between inter-ictal EEGs of AE patients and resting-state EEGs of HCs and between pre- and post-seizure EEGs in AE patients. The EEG microstates of epileptic patients before and after absence seizures are characterized by a "slowdown" in transitions between microstates. Microstates might be used as an index to evaluate the temporal and spatial recovery process of absence seizures in AE.
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http://dx.doi.org/10.1016/j.seizure.2021.03.020DOI Listing
May 2021

Long non-coding RNA LINC01137 contributes to oral squamous cell carcinoma development and is negatively regulated by miR-22-3p.

Cell Oncol (Dordr) 2021 Apr 2. Epub 2021 Apr 2.

Department of Pathology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Purpose: Long noncoding RNAs (lncRNAs) are emerging as key regulators in cancer initiation and progression. LINC01137 is a recently identified lncRNA of which the functional role in the development of oral squamous cell carcinoma (OSCC) has not been determined yet.

Methods: We analyzed the expression of LINC01137 using a microarray-based OSCC gene expression dataset (GSE31056), and validated the results obtained using RT-qPCR in 26 pairs of primary OSCC tumor tissues and adjacent non-tumor tissues. The proliferative and invasive effects of LINC01137 on OSCC cells were determined using CCK-8, colony formation and transwell assays, respectively. Targeted binding between miR-22-3p and LINC01137 was verified using a dual luciferase reporter assay.

Results: We found that LINC01137 was significantly upregulated in primary OSCCs. LINC01137 knockdown inhibited OSCC cell proliferation, migration and invasion, whereas LINC01137 overexpression induced opposite effects. LINC01137 upregulation along with p53 inhibition enhanced the malignant transformation of oral cells. In addition, we found that miR-22-3p can directly target LINC01137 through interaction with a putative miR-22-3p-binding site present within the LINC01137 sequence. A significant negative correlation was observed between LINC01137 and miR-22-3p expression in primary OSCC specimens. Exogenous overexpression of miR-22-3p markedly reduced the endogenous expression level of LINC01137 in OSCC cells. Additional functional assays showed that miR-22-3p overexpression enhanced the inhibitory effect of siRNA-mediated LINC01137 silencing on OSCC cell proliferation, migration and invasion, whereas miR-22-3p inhibition had the opposite effect.

Conclusions: Our results indicate that LINC01137 functions as an oncogenic lncRNA in OSCC. miR-22-3p can directly target LINC01137 and negatively regulate its expression and function.
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http://dx.doi.org/10.1007/s13402-021-00586-0DOI Listing
April 2021

Atrial Arrhythmias in Patients with Severe COVID-19.

Cardiol Res Pract 2021 12;2021:8874450. Epub 2021 Mar 12.

Department of Cardiology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.

The number of confirmed COVID-19 cases has increased drastically; however, information regarding the impact of this disease on the occurrence of arrhythmias is scarce. The aim of this study was to determine the impact of COVID-19 on arrhythmia occurrence. This prospective study included patients with COVID-19 treated at the Leishenshan Temporary Hospital of Wuhan City, China, from February 24 to April 5, 2020. Demographic, comorbidity, and arrhythmias data were collected from patients with COVID-19 ( = 84) and compared with control data from patients with bacterial pneumonia ( = 84) infection. Furthermore, comparisons were made between patients with severe and nonsevere COVID-19 and between older and younger patients. Compared with patients with bacterial pneumonia, those with COVID-19 had higher total, mean, and minimum heart rates (all < 0.01). Patients with severe COVID-19 (severe and critical type diseases) developed more atrial arrhythmias compared with those with nonsevere symptoms. Plasma creatine kinase isoenzyme (CKMB) levels (=0.01) were higher in the severe group than in the nonsevere group, and there were more deaths in the severe group than in the nonsevere group (6 (15%) vs. 3 (2.30%); =0.05). Premature atrial contractions (PAC) and nonsustained atrial tachycardia (NSAT) were significantly positively correlated with plasma CKMB levels but not with high-sensitive cardiac troponin I or myoglobin levels. Our data demonstrate that COVID-19 patients have higher total, mean, and minimum heart rates compared with those with bacterial pneumonia. Patients with severe or critical disease had more frequent atrial arrhythmias (including PAC and AF) and higher CKMB levels and mortality than those with nonsevere symptoms.
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http://dx.doi.org/10.1155/2021/8874450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955658PMC
March 2021

Are depressive symptoms associated with quality of care in diabetes? Findings from a nationwide population-based study.

BMJ Open Diabetes Res Care 2021 Mar;9(1)

Department of Epidemiology and Health Monitoring, Robert Koch Institute, Berlin, Germany

Introduction: We investigated whether the presence of depressive symptoms among adults with diagnosed diabetes is associated with adverse quality of diabetes care.

Research Design And Methods: The study population was drawn from the German national health survey 'German Health Update' 2014/2015-European Health Interview Survey and included 1712 participants aged ≥18 years with self-reported diabetes during the past 12 months. Depressive symptoms in the past 2 weeks were assessed by the eight-item depression module of the Patient Health Questionnaire (PHQ-8), with PHQ-8 sum score values ≥10 indicating current depressive symptoms. We selected 12 care indicators in diabetes based on self-reported information on care processes and outcomes. Associations of depressive symptoms with those indicators were examined in multivariable logistic regression models with stepwise adjustments.

Results: Overall, 15.6% of adults with diagnosed diabetes reported depressive symptoms, which were higher in women than in men (18.7% vs 12.9%). Adjusted for age, sex, education, social support, health-related behaviors, and diabetes duration, adults with depressive symptoms were more likely to report acute hypoglycemia (OR 1.81, 95% CI 1.13 to 2.88) or hyperglycemia (OR 2.10, 95% CI 1.30 to 3.37) in the past 12 months, long-term diabetes complications (OR 2.30, 95% CI 1.55 to 3.39) as well as currently having a diet plan (OR 2.14, 95% CI 1.39 to 3.29) than adults without depressive symptoms. Significant associations between depressive symptoms and other care indicators were not observed.

Conclusions: The present population-based study of adults with diagnosed diabetes indicates an association between depressive symptoms and adverse diabetes-specific care with respect to outcome but largely not to process indicators. Our findings underline the need for intensified care for persons with diabetes and depressive symptoms. Future research needs to identify underlying mechanisms with a focus on the inter-relationship between diabetes, depression and diabetes-related distress.
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http://dx.doi.org/10.1136/bmjdrc-2020-001804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986897PMC
March 2021

Thermodynamics Controlled Sharp Transformation from InP to GaP Nanowires via Introducing Trace Amount of Gallium.

Nanoscale Res Lett 2021 Mar 20;16(1):49. Epub 2021 Mar 20.

State Key Laboratory of Powder Metallurgy, Central South University, Changsha, 410083, China.

Growth of high-quality III-V nanowires at a low cost for optoelectronic and electronic applications is a long-term pursuit of research. Still, controlled synthesis of III-V nanowires using chemical vapor deposition method is challenge and lack theory guidance. Here, we show the growth of InP and GaP nanowires in a large area with a high density using a vacuum chemical vapor deposition method. It is revealed that high growth temperature is required to avoid oxide formation and increase the crystal purity of InP nanowires. Introduction of a small amount of Ga into the reactor leads to the formation of GaP nanowires instead of ternary InGaP nanowires. Thermodynamic calculation within the calculation of phase diagrams (CALPHAD) approach is applied to explain this novel growth phenomenon. Composition and driving force calculations of the solidification process demonstrate that only 1 at.% of Ga in the catalyst is enough to tune the nanowire formation from InP to GaP, since GaP nucleation shows a much larger driving force. The combined thermodynamic studies together with III-V nanowire growth studies provide an excellent example to guide the nanowire growth.
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http://dx.doi.org/10.1186/s11671-021-03505-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981363PMC
March 2021

Patterns and associated factors of diabetes self-management: Results of a latent class analysis in a German population-based study.

PLoS One 2021 19;16(3):e0248992. Epub 2021 Mar 19.

Institute of General Practice and Family Medicine, Medical Faculty of Martin Luther-University Halle-Wittenberg, Halle (Saale), Germany.

Objective: Few studies on diabetes self-management considered the patterns and relationships of different self-management behaviours (SMB). The aims of the present study are 1) to identify patterns of SMB among persons with diabetes, 2) to identify sociodemographic and disease-related predictors of SMB among persons with diabetes.

Research Design And Methods: The present analysis includes data of 1,466 persons (age 18 to 99 years; 44.0% female; 56.0% male) with diabetes (type I and II) from the population-based study German Health Update 2014/2015 (GEDA 2014/2015-EHIS). We used latent class analysis in order to distinguish different patterns of self-management behaviours among persons with diabetes. The assessment of SMB was based on seven self-reported activities by respondents (dietary plan, diabetes-diary, diabetes health pass, self-assessment of blood glucose, self-examination of feet, retinopathy-screenings and assessment of HbA1c). Subsequent multinomial latent variable regressions identified factors that were associated with self-management behaviour.

Results: Latent class analysis suggested a distinction between three patterns of SMB. Based on modal posterior probabilities 42.8% of respondents showed an adherent pattern of diabetes self-management with above-average frequency in all seven indicators of SMB. 32.1% showed a nonadherent pattern with a below-average commitment in all seven forms of SMB. Another 25.1% were assigned to an ambivalent type, which showed to be adherent with regard to retinopathy screenings, foot examinations, and the assessment of HbA1c, yet nonadherent with regard to all other forms of SMB. In multivariable regression analyses, participation in Diabetes Self-Management Education programs (DSME) was the most important predictor of good self-management behaviour (marginal effect = 51.7 percentage points), followed by attentiveness towards one's personal health (31.0 percentage points). Respondents with a duration of illness of less than 10 years (19.5 percentage points), employed respondents (7.5 percentage points), as well as respondents with a high socioeconomic status (24.7 percentage points) were more likely to show suboptimal forms of diabetes self-management.

Discussion: In the present nationwide population-based study, a large proportion of persons with diabetes showed suboptimal self-management behaviour. Participation in a DSME program was the strongest predictor of good self-management. Results underline the need for continual and consistent health education for patients with diabetes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248992PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978380PMC
March 2021

Imaging of Fibroblast Activation Protein in Cancer Xenografts Using Novel (4-Quinolinoyl)-glycyl-2-cyanopyrrolidine-Based Small Molecules.

J Med Chem 2021 04 17;64(7):4059-4070. Epub 2021 Mar 17.

Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States.

Fibroblast activation protein (FAP) has become a favored target for imaging and therapy of malignancy. We have synthesized and characterized two new (4-quinolinoyl)-glycyl-2-cyanopyrrolidine-based small molecules for imaging of FAP, and [In], using optical and single-photon computed tomography/CT, respectively. Binding of imaging agents to FAP was assessed in six human cancer cell lines of different cancer types: glioblastoma (U87), melanoma (SKMEL24), prostate (PC3), NSCLC (NCIH2228), colorectal carcinoma (HCT116), and lung squamous cell carcinoma (NCIH226). Mouse xenograft models were developed with FAP-positive U87 and FAP-negative PC3 cells to test pharmacokinetics and binding specificity . and [In] demonstrated nanomolar inhibition of FAP at values of 1.26 and 16.20 nM, respectively. Both were selective for FAP over DPP-IV, a related serine protease. Both enabled imaging of FAP-expressing tumors specifically . [In] showed high uptake at 18.2 percent injected dose per gram in the U87 tumor at 30 min post-administration.
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http://dx.doi.org/10.1021/acs.jmedchem.0c02171DOI Listing
April 2021

Epigallocatechin-3-Gallate Dampens Non-Alcoholic Fatty Liver by Modulating Liver Function, Lipid Profile and Macrophage Polarization.

Nutrients 2021 Feb 11;13(2). Epub 2021 Feb 11.

Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA.

Epigallocatechin-3-gallate (EGCG) has been shown to attenuate obesity, fatty liver disease, hepatic inflammation and lipid profiles. Here, we validate the efficacy of EGCG in a murine model of non-alcoholic fatty liver disease (NAFLD) and extend the mechanistic insights. NAFLD was induced in mice by a high-fat diet (HFD) with 30% fructose. EGCG was administered at a low dose (25 mg/kg/day, EGCG-25) or high dose (50 mg/kg/day, EGCG-50) for 8 weeks. In HFD-fed mice, EGCG attenuated body and liver weight by ~22% and 47%, respectively, accompanied by ~47% reduction in hepatic triglyceride (TG) accumulation and ~38% reduction in serum cholesterol, resonating well with previous reports in the literature. In EGCG-treated mice, the hepatic steatosis score and the non-alcoholic steatohepatitis activity score were both reduced by ~50% and ~57%, respectively, accompanied by improvements in hepatic inflammation grade. Liver enzymes were improved ~2-3-fold following EGCG treatment, recapitulating previous reports. Hepatic flow cytometry demonstrated that EGCG-fed mice had lower Ly6C, MHCII+ and higher CD206, CD23 hepatic macrophage infiltration, indicating that EGCG impactedM1/M2 macrophage polarization. Our study further validates the salubrious effects of EGCG on NAFLD and sheds light on a novel mechanistic contribution of EGCG, namely hepatic M1-to-M2 macrophage polarization. These findings offer further support for the use of EGCG in human NAFLD.
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http://dx.doi.org/10.3390/nu13020599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918805PMC
February 2021

Heightened Crescentic Glomerulonephritis in Immune Challenged 129sv Mice Is TGF-β/Smad3 Dependent.

Int J Mol Sci 2021 Feb 19;22(4). Epub 2021 Feb 19.

The Department of Biomedical Engineering, University of Houston, Houston, TX 77204-5060, USA.

The 129sv mouse strain is particularly sensitive to experimental immune-mediated nephritis. Previous studies have indicated that transforming growth factor-β (TGF-β) plays a critical role in both immune modulation and tissue fibrogenesis in various diseases and that its biological activities are exerted via the SMAD family. In this study, we aimed to determine whether TGF-β/SMAD signaling is essential for the development of immune-mediated nephritis in 129sv mice. Relative to C57BL/6J control mice with anti-glomeruli basement membrane (GBM) nephritis, 129sv mice with anti-GBM nephritis exhibited increased renal collagen deposition. Additionally, higher mRNA levels of pro-collagen and collagen IV, higher serum levels of active and total TGF-β1, and increased TGF-β1, TGF-βIIR, and phosphorylated SMAD expression were detected in these mice. Deletion of in 129sv mice ameliorated anti-GBM induced nephritis, including crescentic glomerulonephritis. Collectively, these findings indicate that the heightened experimental nephritis and fibrotic disease in the 129sv strain of mice are regulated by SMAD3, which could be a potential therapeutic target for immune-mediated nephritis.
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http://dx.doi.org/10.3390/ijms22042059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922100PMC
February 2021

First-in-human neuroimaging of soluble epoxide hydrolase using [F]FNDP PET.

Eur J Nucl Med Mol Imaging 2021 Feb 13. Epub 2021 Feb 13.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

Purpose: Soluble epoxide hydrolase (sEH) is an enzyme with putative effect on neuroinflammation through its influence on the homeostasis of polyunsaturated fatty acids and related byproducts. sEH is an enzyme that metabolizes anti-inflammatory epoxy fatty acids to the corresponding, relatively inert 1,2-diols. A high availability or activity of sEH promotes vasoconstriction and inflammation in local tissues that may be linked to neuropsychiatric diseases. We developed [F]FNDP to study sEH in vivo with positron emission tomography (PET).

Methods: Brain PET using bolus injection of [F]FNDP followed by emission imaging lasting 90 or 180 min was completed in healthy adults (5 males, 2 females, ages 40-53 years). The kinetic behavior of [F]FNDP was evaluated using a radiometabolite-corrected arterial plasma input function with compartmental or graphical modeling approaches.

Results: [F]FNDP PET was without adverse effects. Akaike information criterion favored the two-tissue compartment model (2TCM) in all ten regions of interest. Regional total distribution volume (V) values from each compartmental model and Logan analysis were generally well identified except for corpus callosum V using the 2TCM. Logan analysis was assessed as the choice model due to stability of regional V values from 90-min data and due to high correlation of Logan-derived regional V values with those from the 2TCM. [F]FNDP binding was higher in human cerebellar cortex and thalamus relative to supratentorial cortical regions, which aligns with reported expression patterns of the epoxide hydrolase 2 gene in human brain.

Conclusion: These data support further use of [F]FNDP PET to study sEH in human brain.
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http://dx.doi.org/10.1007/s00259-021-05231-4DOI Listing
February 2021

Blame Attribution Asymmetry in Human-Automation Cooperation.

Authors:
Peng Liu Yong Du

Risk Anal 2021 Jan 13. Epub 2021 Jan 13.

College of Management and Economics, Tianjin University, Tianjin, China.

Human-automation cooperation has become ubiquitous. In this concept, automation refers to autonomous machines, robots, artificial intelligence, and other autonomous nonhuman agents. A human driver will share control of semiautonomous vehicles (semi-AVs) with an automated system and thus share responsibility for crashes caused by semi-AVs. Research has not clarified whether and why people would attribute different levels of blame and responsibility to automation (and its creators) and its human counterpart when each causes an equivalent crash. We conducted four experiments in two studies (total N = 1,045) to measure different responses (e.g., severity and acceptability judgment, blame and responsibility attribution, compensation judgment) to hypothetical crashes that are caused by the human or the automation in semi-AVs. The results provided previously unidentified evidence of a bias, which we called the "blame attribution asymmetry," a tendency that people will judge the automation-caused crash more harshly, ascribe more blame and responsibility to automation and its creators, and think the victim in this crash should be compensated more. This asymmetry arises in part because of the higher negative affect triggered by the automation-caused crash. This bias has a direct policy implication: a policy allowing "not-safe enough" semi-AVs on roads could backfire, because these AVs will lead to many traffic crashes, which might in turn produce greater psychological costs and deter more people from adopting them. Other theoretical and policy implications of our findings were also discussed.
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http://dx.doi.org/10.1111/risa.13674DOI Listing
January 2021

Effects of Primary Decompressive Craniectomy on the Outcomes of Serious Traumatic Brain Injury with Mass Lesions, and Independent Predictors of Operation Decision.

World Neurosurg 2021 Apr 7;148:e396-e405. Epub 2021 Jan 7.

Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address:

Background: Although operative indications for traumatic brain injury (TBI) are known, neurosurgeons are unsure whether to remove the bone flap after mass lesion extraction, and an efficient scoring system for predicting which patients should undergo decompressive craniectomy (DC) does not exist.

Methods: Nine parameters were assessed. In total, 245 patients with severe TBI were retrospectively assessed from June 2015 to May 2019, who underwent DC or craniotomy to remove mass lesions. The 6-month mortality and Extended Glasgow Outcome Scale scores were compared between the DC and craniotomy groups. Using univariable and multivariable logistic regression equations, receiver operating characteristic curves were obtained for predicting the decision for DC.

Results: The overall 6-month mortality in the entire cohort was 11.43% (28/245). Patients undergoing DC had lower mean preoperative Glasgow Coma Scale scores (P = 0.01), and higher amounts of individuals with a Glasgow Coma Scale score of 6 (P = 0.007), unresponsive pupillary light reflex (P < 0.001), closed basal cisterns (P < 0.001), and diffuse injury (P = 0.025), compared with the craniotomy group. Because of high disease severity, individuals administered primary DC showed increased 6-month mortality compared with the craniotomy group. However, in surviving patients, favorable Extended Glasgow Outcome Scale rates were similar in both groups. Pupillary light reflex and basal cisterns were independent predictors of the DC decision. Based on receiver operating characteristic curves, the model had sensitivity and specificity of 81.6% and 84.9%, respectively, in predicting the probability of DC.

Conclusions: These preliminary data showed that primary DC may benefit some patients with severe TBI with mass lesions. In addition, unresponsive preoperative pupil reaction and closed basal cistern could predict the DC decision.
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http://dx.doi.org/10.1016/j.wneu.2020.12.158DOI Listing
April 2021

A Learned Reconstruction Network for SPECT Imaging.

IEEE Trans Radiat Plasma Med Sci 2021 Jan 12;5(1):26-34. Epub 2020 May 12.

Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 USA.

A neural network designed specifically for SPECT image reconstruction was developed. The network reconstructed activity images from SPECT projection data directly. Training was performed through a corpus of training data including that derived from digital phantoms generated from custom software and the corresponding projection data obtained from simulation. When using the network to reconstruct images, input projection data were initially fed to two fully connected (FC) layers to perform a basic reconstruction. Then the output of the FC layers and an attenuation map were delivered to five convolutional layers for signal-decay compensation and image optimization. To validate the system, data not used in training, simulated data from the Zubal human brain phantom, and clinical patient data were used to test reconstruction performance. Reconstructed images from the developed network proved closer to the truth with higher resolution and quantitative accuracy than those from conventional OS-EM reconstruction. To understand better the operation of the network for reconstruction, intermediate results from hidden layers were investigated for each step of the processing. The network system was also retrained with noisy projection data and compared with that developed with noise-free data. The retrained network proved even more robust after having learned to filter noise. Finally, we showed that the network still provided sharp images when using reduced view projection data (retrained with reduced view data).
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http://dx.doi.org/10.1109/trpms.2020.2994041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781067PMC
January 2021

Novel insights into the role of Clostridium novyi-NT related combination bacteriolytic therapy in solid tumors.

Oncol Lett 2021 Feb 11;21(2):110. Epub 2020 Dec 11.

Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.

Several solid tumors (for example leiomyosarcoma, melanoma and hepatocellular carcinoma) possess areas of hypoxia, which underlies one of the primary reasons of failure of conventional anticancer therapies. The areas of poor vascularization are insensitive to radiotherapy and chemotherapeutic drugs. Conversely, the hypoxic regions of tumors provide an ideal environment for anaerobic bacteria. The attenuated anaerobic bacterium, Clostridium novyi-NT (C. novyi-NT), is highly sensitive to oxygen and can target the destruction of hypoxic and necrotic areas of tumors, inducing oncolysis and characteristics indicative of an immune response. Theoretically, chemotherapy, radiotherapy and immunotherapy combined with bacterial therapy can be used as a novel means of treating solid tumors, promoting tumor regression and inhibiting metastasis formation with a notable beneficial effect. The present review discusses the molecular mechanisms of combined bacteriolytic therapy, predominantly focusing on C. novyi-NT, and summarizes the findings of previous studies on experimental animal models, including its efficacy and safety via different drug delivery routes. This strategy has great potential to overcome the limitations of conventional cancer therapy, resulting in improved treatments, and thus potentially improved outcomes for patients.
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http://dx.doi.org/10.3892/ol.2020.12371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751347PMC
February 2021

20-HETE synthesis inhibition attenuates traumatic brain injury-induced mitochondrial dysfunction and neuronal apoptosis via the SIRT1/PGC-1α pathway: A translational study.

Cell Prolif 2021 Feb 13;54(2):e12964. Epub 2020 Dec 13.

Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.

Objectives: 20-hydroxyeicosatetraenoic acid (20-HETE) is a metabolite of arachidonic acid catalysed by cytochrome P450 enzymes and plays an important role in cell death and proliferation. We hypothesized that 20-HETE synthesis inhibition may have protective effects in traumatic brain injury (TBI) and investigated possible underlying molecular mechanisms.

Materials And Methods: Neurologic deficits, and lesion volume, reactive oxygen species (ROS) levels and cell death as assessed using immunofluorescence staining, transmission electron microscopy and Western blotting were used to determine post-TBI effects of HET0016, an inhibitor of 20-HETE synthesis, and their underlying mechanisms.

Results: The level of 20-HETE was found to be increased significantly after TBI in mice. 20-HETE synthesis inhibition reduced neuronal apoptosis, ROS production and damage to mitochondrial structures after TBI. Mechanistically, HET0016 decreased the Drp1 level and increased the expression of Mfn1 and Mfn2 after TBI, indicating a reversal of the abnormal post-TBI mitochondrial dynamics. HET0016 also promoted the restoration of SIRT1 and PGC-1α in vivo, and a SIRT1 activator (SRT1720) reversed the downregulation of SIRT1 and PGC-1α and the abnormal mitochondrial dynamics induced by 20-HETE in vitro. Furthermore, plasma 20-HETE levels were found to be higher in TBI patients with unfavourable neurological outcomes and were correlated with the GOS score.

Conclusions: The inhibition of 20-HETE synthesis represents a novel strategy to mitigate TBI-induced mitochondrial dysfunction and neuronal apoptosis by regulating the SIRT1/PGC-1α pathway.
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http://dx.doi.org/10.1111/cpr.12964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848954PMC
February 2021

Dysbiosis characteristics of gut microbiota in cerebral infarction patients.

Transl Neurosci 2020 8;11(1):124-133. Epub 2020 Jun 8.

Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.

Objective: The aim of this study is to investigate the dysbiosis characteristics of gut microbiota in patients with cerebral infarction (CI) and its clinical implications.

Methods: Stool samples were collected from 79 CI patients and 98 healthy controls and subjected to 16S rRNA sequencing to identify stool microbes. Altered compositions and functions of gut microbiota in CI and its correlation with clinical features were investigated. Random forest and receiver operating characteristic analysis were used to develop a diagnostic model.

Results: Microbiota diversity and structure between CI patients and healthy controls were overall similar. However, butyrate-producing bacteria (BPB) were significantly reduced in CI patients, while lactic acid bacteria (LAB) were increased. Genetically, BPB-related functional genes were reduced in CI patients, whereas LAB-related genes were enhanced. The interbacterial correlations among BPB in CI patients were less prominent than those in healthy controls. Clinically, BPB was negatively associated with the National Institutes of Health Stroke Scale (NIHSS), while LAB was positively correlated with NIHSS. Both BPB and LAB played leading roles in the diagnostic model based on 47 bacteria.

Conclusions: The abundance and functions of BPB in CI patients were significantly decreased, while LAB were increased. Both BPB and LAB displayed promising potential in the assessment and diagnosis of CI.
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http://dx.doi.org/10.1515/tnsci-2020-0117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706127PMC
June 2020

G9a Promotes Invasion and Metastasis of Non-Small Cell Lung Cancer through Enhancing Focal Adhesion Kinase Activation via NF-κB Signaling Pathway.

Mol Cancer Res 2021 03 9;19(3):429-440. Epub 2020 Dec 9.

Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, California.

Potential roles of euchromatic histone methyltransferase 2 ( or G9a) in invasion and metastasis are not well understood in non-small cell lung cancer (NSCLC). Here, we investigated the effect and underlying mechanisms of G9a and therapeutic implications of targeting G9a in the invasion and metastasis of NSCLC. Overexpression of G9a significantly enhanced proliferation and invasion, while knockdown of G9a drastically suppressed growth and metastasis of A549 and H1299 NSCLC cells. Knockdown or inhibition of G9a significantly decreased the expression of focal adhesion kinase (FAK) protein and activation of FAK pathway. In addition, defactinib, a potent FAK inhibitor, partially abolished the G9a-enhanced invasion in these NSCLC cells. Furthermore, targeting G9a was found to suppress NF-κB transcriptional activity in NSCLC cells through stabilizing NF-κB inhibitor alpha (IκBα), while an NF-κB inhibitor Parthenilide partially abolished the G9a-enhanced FAK activation, which suggests that G9a-enhanced invasion and activation of FAK is mediated by elevated NF-κB activity. Notably, a strong positive correlation between the IHC staining of G9a and phosphorylated FAK proteins was identified in H1299 xenografts and 159 cases of NSCLC tissues (R = 0.408). IMPLICATIONS: The findings of this study strongly demonstrate that G9a may promote invasion and metastasis of NSCLC cells by enhancing FAK signaling pathway via elevating NF-κB transcriptional activity, indicating potential significance and therapeutic implications of these pathways in the invasion and metastasis of NSCLCs that overexpress G9a protein.
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http://dx.doi.org/10.1158/1541-7786.MCR-20-0557DOI Listing
March 2021