Publications by authors named "Heng Yang"

214 Publications

Progression in Moyamoya Disease: Clinical Feature, Neuroimaging Evaluation and Treatment.

Curr Neuropharmacol 2021 Jul 15. Epub 2021 Jul 15.

Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, China.

Moyamoya disease (MMD) is a chronic cerebrovascular disease characterized by progressive stenosis of the arteries of the circle of Willis, with the formation of the collateral vascular network at the base of the brain. Its clinical manifestations are complicated. Numerous studies have attempted to clarify the clinical features of MMD, including its epidemiology, genetic characteristics, and pathophysiology. With the development of neuroimaging techniques, various neuroimaging modalities with different advantages have deepened the understanding of MMD in structural, functional, spatial, and temporal dimensions. At present, the main treatment for MMD focuses on neurological protection, cerebral blood flow reconstruction, and neurological rehabilitation, such as pharmacological treatment, surgical revascularization, and cognitive rehabilitation. In this review, we discuss recent progress in understanding the clinical features, neuroimaging evaluation, and treatment of MMD.
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http://dx.doi.org/10.2174/1570159X19666210716114016DOI Listing
July 2021

ADP-ribosyltransferase PARP11 suppresses Zika virus in synergy with PARP12.

Cell Biosci 2021 Jun 29;11(1):116. Epub 2021 Jun 29.

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA.

Background: Zika virus (ZIKV) infection and ZIKV epidemic have been continuously spreading silently throughout the world and its associated microcephaly and other serious congenital neurological complications poses a significant global threat to public health. Type I interferon response to ZIKV infection in host cells suppresses viral replication by inducing the expression of interferon-stimulated genes (ISGs).

Methods: The study aims to demonstrate the anti-ZIKV mechanism of PARP11. PARP11 knock out and overexpressing A549 cell lines were constructed to evaluate the anti-ZIKV function of PARP11. PARP11, PARP12 and PARP11PARP12 HEK293T cell lines were constructed to explain the synergistic effect of PARP11 and PARP12 on NS1 and NS3 protein degradation. Western blotting, immunofluorescence and immunoprecipitation assay were performed to illustrate the interaction between PARP11 and PARP12.

Results: Both mRNA and protein levels of PARP11 were induced in WT but not IFNAR1 cells in response to IFNα or IFNβ stimulation and ZIKV infection. ZIKV replication was suppressed in cells expressed PARP11 but was enhanced in PARP11 cells. PARP11 suppressed ZIKV independently on itself PARP enzyme activity. PARP11 interacted with PARP12 and promoted PARP12-mediated ZIKV NS1 and NS3 protein degradation.

Conclusion: We identified ADP-ribosyltransferase PARP11 as an anti-ZIKV ISG and found that it cooperated with PARP12 to enhance ZIKV NS1 and NS3 protein degradation. Our findings have broadened the understanding of the anti-viral function of ADP-ribosyltransferase family members, and provided potential therapeutic targets against viral ZIKV infection.
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http://dx.doi.org/10.1186/s13578-021-00628-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240438PMC
June 2021

Automated Quantitative Analysis of Blood Flow in Extracranial-Intracranial Arterial Bypass Based on Indocyanine Green Angiography.

Front Surg 2021 11;8:649719. Epub 2021 Jun 11.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

Microvascular imaging based on indocyanine green is an important tool for surgeons who carry out extracranial-intracranial arterial bypass surgery. In terms of blood perfusion, indocyanine green images contain abundant information, which cannot be effectively interpreted by humans or currently available commercial software. In this paper, an automatic processing framework for perfusion assessments based on indocyanine green videos is proposed and consists of three stages, namely, vessel segmentation based on the UNet deep neural network, preoperative and postoperative image registrations based on scale-invariant transform features, and blood flow evaluation based on the Horn-Schunck optical flow method. This automatic processing flow can reveal the blood flow direction and intensity curve of any vessel, as well as the blood perfusion changes before and after an operation. Commercial software embedded in a microscope is used as a reference to evaluate the effectiveness of the algorithm in this study. A total of 120 patients from multiple centers were sampled for the study. For blood vessel segmentation, a Dice coefficient of 0.80 and a Jaccard coefficient of 0.73 were obtained. For image registration, the success rate was 81%. In preoperative and postoperative video processing, the coincidence rates between the automatic processing method and commercial software were 89 and 87%, respectively. The proposed framework not only achieves blood perfusion analysis similar to that of commercial software but also automatically detects and matches blood vessels before and after an operation, thus quantifying the flow direction and enabling surgeons to intuitively evaluate the perfusion changes caused by bypass surgery.
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http://dx.doi.org/10.3389/fsurg.2021.649719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225942PMC
June 2021

Transcriptome-based identification and expression characterization of RgABCC transporters in Rehmannia glutinosa.

PLoS One 2021 25;16(6):e0253188. Epub 2021 Jun 25.

College of Bioengineering, Henan University of Technology, Zhengzhou High-technology Zero, Henan Province, 450001, China.

ABCC multidrug resistance-associated proteins (ABCCs/MRPs), a subfamily of ABC transporters, are involved in multiple physiological processes. Although these proteins have been characterized in some plants, limited efforts have been made to address their possible roles in Rehmannia glutinosa, a medicinal plant. Here, we scanned R. glutinosa transcriptome sequences and identified 18 RgABCC genes by in silico analysis. Sequence alignment revealed that the RgABCCs were closely phylogenetically related and highly conserved with other plant ABCCs/MRPs. Subcellular localization revealed that most of the RgABCCs were deposited in vacuoles and a few in plasma membranes. Tissue-specific expression of the RgABCCs indicated significant specific accumulation patterns, implicating their roles in the respective tissues. Differential temporal expression patterns of the RgABCCs exhibited their potential roles during root development. Various abiotic stress and hormone treatment experiments indicated that some RgABCCs could be transcriptionally regulated in roots. Furthermore, the transcription of several RgABCCs in roots was strongly activated by cadmium (Cd), suggesting possible roles under heavy metal stresses. Functional analysis of RgABCC1 heterologous expression revealed that it may increase the tolerance to Cd in yeast, implying its Cd transport activity. Our study provides a detailed inventory and molecular characterization of the RgABCCs and valuable information for exploring their functions in R. glutinosa.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253188PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232422PMC
June 2021

Onset Investigation on Dynamic Change of Biohythane Generation and Microbial Structure in Dual-chamber versus Single-chamber Microbial Electrolysis Cells.

Water Res 2021 Jun 4;201:117326. Epub 2021 Jun 4.

State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing, 100084, China. Electronic address:

Biohythane is alternative fuel to replace fossil fuel for car combustion, and biohythane generation could be potential pathway for energy recovery from wastewater treatment. Microbial electrolysis cell (MEC) is electrochemical technique to convert waste to methane and hydrogen gas for biohythane generation, but the feasibility and stability of MEC needs further investigation to assure sustainable energy recovery. System configuration is paramount factor for electrochemical reaction and mass transfer, and this study was to investigate the configuration impact (single vs dual chamber) of MEC for biohythane generation rate and stability. This study showed that dual-chamber MEC could separate methane and hydrogen gas production in the anode and cathode, and combined both together to produce biohythane. To reduce ohmic resistance for higher current, cation exchange membrane (CEM) was removed from dual-chamber to single-chamber MEC. However, free hydrogen diffusion was allowed in the single chamber since CEM was removed. The diffused hydrogen and substrate towards the cathode would favor the methanogen growth, and thus the hydrogen was consumed to reduce the biohythane generation and energy recovery efficiency (i.e., 7.5 × 10 reduced to 5.7 × 10 kWh kg degraded COD day after converting dual-chamber to single-chamber MEC). Absolute abundance of methanogen in single-chamber MEC was greatly boosted, as Methanosarcina and Methanobacteriale on the anode surface, increased by 132% and 243%, respectively, while the original dual-chamber MEC could maintain Geobacter growth for high current generation. This is the keystone study to demonstrate the importance of dual-chamber MEC for the feasibility and stability for the biohythane generation, building up the foundation to use electrochemical device to convert the organic waste to the alternative biohythane.
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http://dx.doi.org/10.1016/j.watres.2021.117326DOI Listing
June 2021

High rate of completion for weekly rifapentine plus isoniazid treatment in Chinese children with latent tuberculosis infection-A single center study.

PLoS One 2021 11;16(6):e0253159. Epub 2021 Jun 11.

Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Three months of weekly rifapentine plus isoniazid (3HP) is a short course regimen for latent tuberculosis infection treatment with satisfied safety and efficacy. However, research on its use in children is limited. In this study, we evaluated the completion rate and safety of the 3HP regimen among children in China. Participants aged 1-14 years receiving 3HP for TB prevention at Shanghai Public Health Clinical Center were followed from December 2019 to November 2020 to evaluate the safety and completion rate of the treatment. Thirty-one children were eligible for inclusion, but five were excluded from the analysis (three were treated with a lower than recommended dose, and two were lost to follow-up). Of the 26 children included in the analysis, the treatment completion rate was 100%. Adverse drug reactions (ADRs) were reported in 38.5% (10/26) of the patients. The most common ADRs were gastrointestinal symptoms (19.2%,5/26), and all ADRs were rated as Grade 1. The 3HP regimen has a high completion rate, and it seems well tolerated in our study population. However, further randomized controlled clinical trial with larger sample size are warranted.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253159PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195436PMC
June 2021

Comparative analysis of differentially expressed miRNAs related to uterine involution in the ovine ovary and uterus.

Arch Anim Breed 2021 12;64(1):167-175. Epub 2021 May 12.

Chongqing academy of animal sciences, Rongchang 402460, Chongqing, China.

To examine the possible miRNA molecular regulatory mechanisms during maternal uterine involution after delivery, we selected ovary and uterus tissues that are structurally connected as experimental materials. We employed Illumina HiSeq sequencing to screen and analyze the quantity and characteristics of miRNA in postpartum ewes in the methylergometrine-treated group and physiological saline control group. Results showed that 16 miRNAs were identified in the ovary libraries, including 4 known miRNAs and 12 novel miRNAs. In the uterus libraries, 54 miRNAs were identified, which included 5 known miRNAs and 49 novel miRNAs. At the same time, target gene prediction, GO annotation, and KEGG signaling pathway enrichment analysis were employed. We found that maternal uterine involution after delivery may involve two miRNA-target gene pairs, i.e., miRNA-200a- and . The YAP1/Hippo signaling pathway is used to construct an ovary-uterine axial regulatory mechanism to regulate the restoration of postpartum maternal uterine morphology and function. In view of this, the identification of miRNAs with significant differences in this study fills a gap in research on miRNAs associated with regulation of postpartum uterine recovery in ewes and provided an important reference for comprehensive understanding and in-depth research on the regulatory molecular network mechanism for postpartum uterine involution in small ruminants.
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http://dx.doi.org/10.5194/aab-64-167-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161056PMC
May 2021

Identification and validation of key miRNAs and miRNA-mRNA regulatory network associated with uterine involution in postpartum Kazakh sheep.

Arch Anim Breed 2021 23;64(1):119-129. Epub 2021 Apr 23.

College of Veterinary Medicine, Southwest University, Rongchang 402460, Chongqing, China.

MicroRNAs (miRNAs) are widely expressed in different mammalian tissues and exert their biological effects through corresponding target genes. miRNA target genes can be rapidly and efficiently identified and screened by combining bioinformatics prediction and experimental validation. To investigate the possible molecular regulatory mechanisms involving miRNAs during uterine involution in postpartum ewes, we used Illumina HiSeq sequencing technology to screen for the number and characteristics of miRNAs in faster uterine involution and normal uterine involution group. A total of 118 differentially expressed miRNAs, including 33 known miRNAs and 85 new miRNAs, were identified in the hypothalamic library, whereas 54 miRNAs, including 5 known miRNAs and 49 new miRNAs, were identified in the uterine library. Screening with four types of gene prediction software revealed 73 target genes associated with uterine involution, and subsequently, GO annotation and KEGG pathway analysis were performed. The results showed that, in the hypothalamic-uterine axis, uterine involution in postpartum ewes might primarily involve two miRNA-target gene pairs, namely, miRNA-200a-PTEN and miRNA-133-FGFR1, which can participate in GnRH signal transduction in the upstream hypothalamus and in the remodeling process at the downstream uterus, through the PI3K-AKT signaling pathway to influence the recovery of the morphology and functions of the uterus during the postpartum period in sheep. Therefore, identification of differentially expressed miRNAs in this study fills a gap in the research related to miRNAs in uterine involution in postpartum ewes and provides an important reference point for a comprehensive understanding of the molecular mechanisms underlying the regulation of postpartum uterine involution in female livestock.
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http://dx.doi.org/10.5194/aab-64-119-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131964PMC
April 2021

Cephalotaxine Inhibits the Survival of Leukemia Cells by Activating Mitochondrial Apoptosis Pathway and Inhibiting Autophagy Flow.

Molecules 2021 May 18;26(10). Epub 2021 May 18.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.

Cephalotaxine (CET) is a natural alkaloid with potent antileukemia effects. However, its underlying molecular mechanism has not been well understood. In this study, we verified that CET significantly inhibited the viability of various leukemia cells, including HL-60, NB4, Jurkat, K562, Raji and MOLT-4. RNA-sequencing and bioinformatics analysis revealed that CET causes mitochondrial function change. Mechanism research indicated that CET activated the mitochondrial apoptosis pathway by reducing the mitochondrial membrane potential, downregulating anti-apoptotic Bcl-2 protein and upregulating pro-apoptotic Bak protein. In addition, the autophagy signaling pathway was highly enriched by RNA-seq analysis. Then, we found that CET blocked the fluorescence colocation of MitoTracker Green and LysoTracker Red and upregulated the level of LC3-II and p62, which indicated that autophagy flow was impaired. Further results demonstrated that CET could impair lysosomal acidification and block autophagy flow. Finally, inhibiting autophagy flow could aggravate apoptosis of HL-60 cells induced by CET. In summary, this study demonstrated that CET exerted antileukemia effects through activation of the mitochondria-dependent pathway and by impairing autophagy flow. Our research provides new insights into the molecular mechanisms of CET in the treatment of leukemia.
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http://dx.doi.org/10.3390/molecules26102996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158396PMC
May 2021

Three-Dimensional Arterial Pulse Signal Acquisition in Time Domain Using Flexible Pressure-Sensor Dense Arrays.

Micromachines (Basel) 2021 May 17;12(5). Epub 2021 May 17.

State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China.

In this study, we developed a radial artery pulse acquisition system based on finger-worn dense pressure sensor arrays to enable three-dimensional pulse signals acquisition. The finger-worn dense pressure-sensor arrays were fabricated by packaging 18 ultra-small MEMS pressure sensors (0.4 mm × 0.4 mm × 0.2 mm each) with a pitch of 0.65 mm on flexible printed circuit boards. Pulse signals are measured and recorded simultaneously when traditional Chinese medicine practitioners wear the arrays on the fingers while palpating the radial pulse. Given that the pitches are much smaller than the diameter of the human radial artery, three-dimensional pulse envelope images can be measured with the system, as can the width and the dynamic width of the pulse signals. Furthermore, the array has an effective span of 11.6 mm-3-5 times the diameter of the radial artery-which enables easy and accurate positioning of the sensor array on the radial artery. This study also outlines proposed methods for measuring the pulse width and dynamic pulse width. The dynamic pulse widths of three volunteers were measured, and the dynamic pulse width measurements were consistent with those obtained by color Doppler ultrasound. The pulse wave velocity can also be measured with the system by measuring the pulse transit time between the pulse signals at the brachial and radial arteries using the finger-worn sensor arrays.
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http://dx.doi.org/10.3390/mi12050569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156466PMC
May 2021

Modulation of Antiviral Immunity and Therapeutic Efficacy by 25-Hydroxycholesterol in Chronically SIV-Infected, ART-Treated Rhesus Macaques.

Virol Sin 2021 May 31. Epub 2021 May 31.

School of Public Health (Shenzhen), Sun Yat-Sen University, Guangdong, 518107, China.

Cholesterol-25-hydroxylase (CH25H) and its enzymatic product 25-hydroxycholesterol (25HC) exert broadly antiviral activity including inhibiting HIV-1 infection. However, their antiviral immunity and therapeutic efficacy in a nonhuman primate model are unknown. Here, we report that the regimen of 25HC combined with antiretroviral therapy (ART), provides profound immunological modulation towards inhibiting viral replication in chronically SIV-infected rhesus macaques (RMs). Compared to the ART alone, this regimen more effectively controlled SIV replication, enhanced SIV-specific cellular immune responses, restored the ratio of CD4/CD8 cells, reversed the hyperactivation state of CD4 T cells, and inhibited the secretion of proinflammatory cytokines by CD4 and CD8 T lymphocytes in chronically SIV-infected RMs. Furthermore, the in vivo safety and the preliminary pharmacokinetics of the 25HC compound were assessed in this RM model. Taken together, these assessments help explain the profound relationship between cholesterol metabolism, immune modulation, and antiviral activities by 25HC. These results provide insight for developing novel therapeutic drug candidates against HIV-1 infection and other related diseases.
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http://dx.doi.org/10.1007/s12250-021-00407-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165512PMC
May 2021

Learning spatiotemporal features of DSA using 3D CNN and BiConvGRU for moyamoya disease detection.

Int J Neurosci 2021 May 27:1-14. Epub 2021 May 27.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

Moyamoya disease (MMD) is a serious intracranial cerebrovascular disease. Cerebral hemorrhage caused by MMD will bring life risk to patients. Therefore, MMD detection is of great significance in the prevention of cerebral hemorrhage. In order to improve the accuracy of digital subtraction angiography (DSA) in the diagnosis of MMD, in this paper, a deep network architecture combined with 3 D convolutional neural network (3 D CNN) and bidirectional convolutional gated recurrent unit (BiConvGRU) is proposed to learn the spatiotemporal features for MMD detection. Firstly, 2 D convolutional neural network (2 D CNN) is utilized to extract spatial features for each frame of DSA. Secondly, the long-term spatiotemporal features of DSA sequence are extracted by BiConvGRU. Thirdly, the short-term spatiotemporal features of DSA are further extracted by 3 D convolutional neural network (3 D CNN). In addition, different features are extracted when gray images and optical flow images pass through the network, and multiple features are extracted by features fusion. Finally, the fused features are utilized to classify. The proposed method was quantitatively evaluated on a data sets of 630 cases. The experimental results showed a detection accuracy of 0.9788, sensitivity and specificity were 0.9780 and 0.9796, respectively, and area under curve (AUC) was 0.9856. Compared with other methods, we can get the highest accuracy and AUC. The experimental results show that the proposed method is stable and reliable for MMD detection, which provides an option for doctors to accurately diagnose MMD.
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http://dx.doi.org/10.1080/00207454.2021.1929214DOI Listing
May 2021

Brucella Outer Membrane Lipoproteins 19 and 16 Differentially Induce IL-18 Response or Pyroptosis in Human Monocytic Cells.

J Infect Dis 2021 May 20. Epub 2021 May 20.

Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China.

Background: Brucella species (B. spp.) are Gram-negative intracellular bacteria, causing severe inflammatory diseases in animals and humans. Two major lipoproteins (L19) and (L16) of Brucella outer membrane proteins (OMPs) were extensively explored in associating with inflammatory response of human monocytes (THP-1).

Methods: Activated THP-1 cells induced with recombinant L19 and L16 were analyzed in comparison with unlipidated forms (U19 and U16) and lipopolysaccharide (LPS) of B. melitensis, respectively.

Results: Secretion of inflammatory factors TNF-α, IL-6 and IL-1β was significantly increased from L19, L16 or both stimulated THP-1 cells. High secretion of IL-18 was detected only from L19-induced cells. Signaling of those cytokine responses was identified mainly through P38-MAPK pathway, and signaling of L19-induced IL-1β response was partly occurred via NF-κB. Exploration for different forms of IL-18 found that L19-induced production of active IL-18 (18 kD) was through up-regulating NLRP3 and activating caspase-1, while L16-induced production of inactive IL-18 fragments (15 kD and 16 kD) occurred through activating caspase-8/3. Additionally, L19 up-regulated phosphorylation of XIAP for inhibiting caspase-3 activity to cleave IL-18, while L16 activated caspase-3 for producing GSDME-N and leading to pyroptosis of THP-1 cells.

Conclusion: Brucella L19 and L16 differentially induce IL-18 response or pyroptosis in THP-1 cells, respectively.
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http://dx.doi.org/10.1093/infdis/jiab272DOI Listing
May 2021

Therapeutic potential of targeting membrane-spanning proteoglycan SDC4 in hepatocellular carcinoma.

Cell Death Dis 2021 05 14;12(5):492. Epub 2021 May 14.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.

Syndecan-4 (SDC4) functions as a major endogenous membrane-associated receptor and widely regulates cytoskeleton, cell adhesion, and cell migration in human tumorigenesis and development, which represents a charming anti-cancer therapeutic target. Here, SDC4 was identified as a direct cellular target of small-molecule bufalin with anti-hepatocellular carcinoma (HCC) activity. Mechanism studies revealed that bufalin directly bond to SDC4 and selectively increased SDC4 interaction with substrate protein DEAD-box helicase 23 (DDX23) to induce HCC genomic instability. Meanwhile, pharmacological promotion of SDC4/DDX23 complex formation also inactivated matrix metalloproteinases (MMPs) and augmented p38/JNK MAPKs phosphorylation, which are highly associated with HCC proliferation and migration. Notably, specific knockdown of SDC4 or DDX23 markedly abolished bufalin-dependent inhibition of HCC proliferation and migration, indicating SDC4/DDX23 signaling axis is highly involved in the HCC process. Our results indicate that membrane-spanning proteoglycan SDC4 is a promising druggable target for HCC, and pharmacological regulation of SDC4/DDX23 signaling axis with small-molecule holds great potential to benefit HCC patients.
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http://dx.doi.org/10.1038/s41419-021-03780-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121893PMC
May 2021

Prognostic Nomogram for Postoperative Patients With Gastroesophageal Junction Cancer of No Distant Metastasis.

Front Oncol 2021 16;11:643261. Epub 2021 Apr 16.

Department of Thoracic Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, China.

Background: Gastroesophageal junction (GEJ) was one of the most common malignant tumors. However, the value of clinicopathological features in predicting the prognosis of postoperative patients with GEJ cancer and without distant metastasis was still unclear.

Methods: The 3425 GEJ patients diagnosed and underwent surgical resection without distant metastasis in the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2015 were enrolled,and they were randomly divided into training and validation cohorts with 7:3 ratio. Univariate and multivariate Cox regression analysis were used to determine the predictive factors that constituted the nomogram. The predictive accuracy and discriminability of Nomogram were determined by the area under the curve (AUC), C index, and calibration curve, and the influence of various factors on prognosis was explored.

Results: 2,400 patients were designed as training cohort and 1025 patients were designed as validation cohort. The percentages of the distribution of demographic and clinicopathological characteristics in the training and validation cohorts tended to be the same. In the training cohort, multivariate Cox regression analysis revealed that the age, tumor grade, T stage and N stage were independent prognostic risk factors for patients with GEJ cancer without distant metastasis. The C index of nomogram model was 0.667. The AUC of the receiver operating characteristic (ROC) analysis for 3- and 5-year overall survival (OS) were 0.704 and 0.71, respectively. The calibration curve of 3- and 5-year OS after operation showed that there was the best consistency between nomogram prediction and actual observation. In the validation cohort, the C index of nomogram model, the AUC of 3- and 5-year OS, and the calibration curve were similar to the training cohort.

Conclusions: Nomogram could evaluate the prognosis of patients with GEJ cancer who underwent surgical resection without distant metastasis.
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http://dx.doi.org/10.3389/fonc.2021.643261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085428PMC
April 2021

Systemic administration of β-glucan induces immune training in microglia.

J Neuroinflammation 2021 Feb 22;18(1):57. Epub 2021 Feb 22.

Department of Biomedical Sciences of Cells & Systems, Section Molecular Neurobiology, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, 9713, AV, Groningen, The Netherlands.

Background: An innate immune memory response can manifest in two ways: immune training and immune tolerance, which refers to an enhanced or suppressed immune response to a second challenge, respectively. Exposing monocytes to moderate-to-high amounts of bacterial lipopolysaccharide (LPS) induces immune tolerance, whereas fungal β-glucan (BG) induces immune training. In microglia, it has been shown that different LPS inocula in vivo can induce either immune training or tolerance. Few studies focused on impact of BG on microglia and were only performed in vitro. The aim of the current study was to determine whether BG activates and induces immune memory in microglia upon peripheral administration in vivo.

Methods: Two experimental designs were used. In the acute design, mice received an intraperitoneal (i.p.) injection with PBS, 1 mg/kg LPS or 20 mg/kg BG and were terminated after 3 h, 1 or 2 days. In the preconditioning design, animals were first challenged i.p. with PBS, 1 mg/kg LPS or 20 mg/kg BG. After 2, 7 or 14 days, mice received a second injection with PBS or 1 mg/kg LPS and were sacrificed 3 h later. Microglia were isolated by fluorescence-activated cell sorting, and cytokine gene expression levels were determined. In addition, a self-developed program was used to analyze microglia morphological changes. Cytokine concentrations in serum were determined by a cytokine array.

Results: Microglia exhibited a classical inflammatory response to LPS, showing significant upregulation of Tnf, Il6, Il1β, Ccl2, Ccl3 and Csf1 expression, three h after injection, and obvious morphological changes 1 and 2 days after injection. With an interval of 2 days between two challenges, both BG and LPS induced immune training in microglia. The training effect of LPS changed into immune tolerance after a 7-day interval between 2 LPS challenges. Preconditioning with BG and LPS resulted in increased morphological changes in microglia in response to a systemic LPS challenge compared to naïve microglia.

Conclusions: Our results demonstrate that preconditioning with BG and LPS both induced immune training of microglia at two days after the first challenge. However, with an interval of 7 days between the first and second challenge, LPS-preconditioning resulted in immune tolerance in microglia.
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http://dx.doi.org/10.1186/s12974-021-02103-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901224PMC
February 2021

Preliminary Study on the Application of Ultrahigh Field Magnetic Resonance in Moyamoya Disease.

Oxid Med Cell Longev 2021 13;2021:5653948. Epub 2021 Jan 13.

Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, China.

Magnetic resonance imaging (MRI) is widely used for the evaluation of moyamoya disease (MMD). In this paper, we describe the features of time-of-flight magnetic resonance angiography (TOF-MRA) and susceptibility-weighted imaging (SWI) at 7 T in a series of MMD patients. In this prospective pilot study, 7 patients (median age: 45.6 years; range: 30-52 years) with MMD and no contraindications for MRI underwent T2-weighted, SWI, and TOF-MRA sequences using a research 7 T head-only scanner. We show that such sequences at ultrahigh field (UHF) represent new and valuable approaches to unravel and characterize MMD. While SWI reveals more remarkable imaging signs related to an improved magnitude and phase contrast imaging, the collateral network pathways in MMD could be excellently delineated using 7 T TOF-MRA. In particular, using SWI and MRA fusion images in UHF MRI helps to improve the detection of bleeding points in hemorrhagic MMD. Our findings indicate that ultrahigh field MRI is very promising to access the severity of the disease and may facilitate revascularization surgery of MMD patients.
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http://dx.doi.org/10.1155/2021/5653948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817260PMC
January 2021

Alda-1 treatment promotes the therapeutic effect of mitochondrial transplantation for myocardial ischemia-reperfusion injury.

Bioact Mater 2021 Jul 8;6(7):2058-2069. Epub 2021 Jan 8.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Mitochondrial damage is a critical driver in myocardial ischemia-reperfusion (I/R) injury and can be alleviated via the mitochondrial transplantation. The efficiency of mitochondrial transplantation is determined by mitochondrial vitality. Because aldehyde dehydrogenase 2 (ALDH2) has a key role in regulating mitochondrial homeostasis, we aimed to investigate its potential therapeutic effects on mitochondrial transplantation via the use of ALDH2 activator, Alda-1. Our present study demonstrated that time-dependent internalization of exogenous mitochondria by cardiomyocytes along with ATP production were significantly increased in response to mitochondrial transplantation. Furthermore, Alda-1 treatment remarkably promoted the oxygen consumption rate and baseline mechanical function of cardiomyocytes caused by mitochondrial transplantation. Mitochondrial transplantation inhibited cardiomyocyte apoptosis induced by the hypoxia-reoxygenation exposure, independent of Alda-1 treatment. However, promotion of the mechanical function of cardiomyocytes exposed to hypoxia-reoxygenation treatment was only observed after mitochondrial Alda-1 treatment and transplantation. By using a myocardial I/R mouse model, our results revealed that transplantation of Alda-1-treated mitochondria into mouse myocardial tissues limited the infarction size after I/R injury, which was at least in part due to increased mitochondrial potential-mediated fusion. In conclusion, ALDH2 activation in mitochondrial transplantation shows great potential for the treatment of myocardial I/R injury.
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http://dx.doi.org/10.1016/j.bioactmat.2020.12.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809100PMC
July 2021

Interleukin-8 as a Biomarker for Disease Prognosis of Coronavirus Disease-2019 Patients.

Front Immunol 2020 8;11:602395. Epub 2021 Jan 8.

Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

The widespread prevalence of coronavirus disease-2019 (COVID-19) which is caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has resulted in a severe global public health emergency. However, there are no sensitive biomarkers to predict the disease prognosis of COVID-19 patients. Here, we have identified interleukin-8 (IL-8) as a biomarker candidate to predict different disease severity and prognosis of COVID-19 patients. While serum IL-6 become obviously elevated in severe COVID-19 patients, serum IL-8 was easily detectible in COVID-19 patients with mild syndromes. Furthermore, lL-8 levels correlated better than IL-6 levels with the overall clinical disease scores at different stages of the same COVID-19 patients. Thus, our studies suggest that IL-6 and IL-8 can be respectively used as biomarkers for severe COVID-19 patients and for COVID-19 disease prognosis.
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http://dx.doi.org/10.3389/fimmu.2020.602395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820901PMC
February 2021

Bluetongue virus non-structural protein 3 (NS3) and NS4 coordinatively antagonize type Ⅰ interferon signaling by targeting STAT1.

Vet Microbiol 2021 Mar 12;254:108986. Epub 2021 Jan 12.

Yunnan Tropical and Subtropical Animal Virus Diseases Laboratory, Yunnan Animal Science and Veterinary Institute, Kunming, Yunnan, 650224, China. Electronic address:

Previous studies have pointed out that bluetongue virus (BTV) down-regulates the expression levels of type Ⅰ interferon (IFN-Ⅰ) and inhibits IFN-Ⅰ signaling by targeting on the Janus tyrosine kinase (JAK)-signal transducer and activator of transcription protein (STAT) pathway. However, individual viral protein could not effectively block IFN-Ⅰ signaling. There is a need to explore the underlying mechanisms by which viral proteins of BTV coordinate to antagonize the IFN-Ⅰ signaling. We investigated the coordinative role of BTV-1 nonstructural protein 3 (NS3) and NS4 in counteracting IFN-Ⅰ signaling in the JAK-STAT pathway by directly interacting with STAT1. The NS3 and NS4 targeted the SH2 domain of STAT1 to inhibit its phosphorylation, heterodimerization, nuclear translocation, as well as activation of downstream genes of the JAK-STAT pathway. NS3 and NS4 impaired STAT1 phosphorylation induced by IFN-Ⅰ in a dose dependent manner. Overall, this study confirmed that NS3 and NS4 of BTV participate in interfering with IFN-Ⅰ signaling process. Also, a new mechanism employed by BTV to evade host innate immune responses was revealed.
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http://dx.doi.org/10.1016/j.vetmic.2021.108986DOI Listing
March 2021

Integrated miRNA-mRNA analysis reveals the roles of miRNAs in the replanting benefit of Achyranthes bidentata roots.

Sci Rep 2021 Jan 15;11(1):1628. Epub 2021 Jan 15.

College of Crop Sciences, Fujian Agriculture and Forestry University, Jinshan Road, Cangshan District, Fuzhou, 350002, China.

The yield and quality of the medicinal plant Achyranthes bidentata can be increased when it is replanted into a field cultivated previously with the same crop, however, fundamental aspects of its biology (so-called "replanting benefit") still remain to be elucidated. miRNAs are sRNA molecules involved in the post-transcriptional regulation of gene expression in plant biological processes. Here, 267 conserved and 36 novel miRNAs were identified in A. bidentata roots. We compared the miRNA content of the roots (R1) from first-year planting with that of the roots (R2) of second-year replanting, and screened 21 differentially expressed (DE) miRNAs. Based on in silico functional analysis, integrated miRNA-mRNA datasets allowed the identification of 10 miRNA-target family modules, which might participate in the benefit. The expression profiles of the miRNA-target modules were potentially correlated with the presence of the replanting benefit. The indication was that the miRNA-responsive continuous monoculture could reprogram miRNA-mRNA expression patterns, which possibly promote the root growth and development, enhance its transport activity and strengthen its tolerance to various stresses, thereby improving A. bidentata productivity as observed in the replanting benefit. Our study provides basic data for further research on the molecular mechanisms of the benefit in A. bidentata.
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http://dx.doi.org/10.1038/s41598-021-81277-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810699PMC
January 2021

Recognition of Cognitive Impairment in Adult Moyamoya Disease: A Classifier Based on High-Order Resting-State Functional Connectivity Network.

Front Neural Circuits 2020 21;14:603208. Epub 2020 Dec 21.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

Vascular cognitive impairment (VCI) is a common complication in adult patients with moyamoya disease (MMD), and is reversible by surgical revascularization in its early stage of mild VCI. However, accurate diagnosis of mild VCI is difficult based on neuropsychological examination alone. This study proposed a method of dynamic resting-state functional connectivity (FC) network to recognize global cognitive impairment in MMD. For MMD, 36 patients with VCI and 43 patients with intact cognition (Non-VCI) were included, as well as 26 normal controls (NCs). Using resting-state fMRI, dynamic low-order FC networks were first constructed with multiple brain regions which were generated through a sliding window approach and correlated in temporal dimension. In order to obtain more information of network interactions along the time, high-order FC networks were established by calculating correlations among each pair of brain regions. Afterwards, a sparse representation-based classifier was constructed to recognize MMD (experiment 1) and its cognitive impairment (experiment 2) with features extracted from both low- and high-order FC networks. Finally, the ten-fold cross-validation strategy was proposed to train and validate the performance of the classifier. The three groups did not differ significantly in demographic features ( > 0.05), while the VCI group exhibited the lowest MMSE scores ( = 0.001). The Non-VCI and NCs groups did not differ significantly in MMSE scores ( = 0.054). As for the classification between MMD and NCs, the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of the classifier reached 90.70, 88.57, 93.67, and 73.08%, respectively. While for the classification between VCI and Non-VCI, the AUC, accuracy, sensitivity, and specificity of the classifier reached 91.02, 84.81, 80.56, and 88.37%, respectively. This study not only develops a promising classifier to recognize VCI in adult MMD in its early stage, but also implies the significance of time-varying properties in dynamic FC networks.
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http://dx.doi.org/10.3389/fncir.2020.603208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779761PMC
December 2020

A Rehmannia glutinosa cinnamate 4-hydroxylase promotes phenolic accumulation and enhances tolerance to oxidative stress.

Plant Cell Rep 2021 Feb 3;40(2):375-391. Epub 2021 Jan 3.

College of Bioengineering, Henan University of Technology, Lianhua Street 100, Zhengzhou High-Technology Zero, Zhengzhou, 450001, Henan, China.

Key Message: RgC4H promotes phenolic accumulation in R. glutinosa, activating the molecular networks of its antioxidant systems, and enhancing the tolerance to oxidative stresses exposed to drought, salinity and HO conditions. Rehmannia glutinosa is of great economic importance in China and increasing R. glutinosa productivity relies, in part, on understanding its tolerance to oxidative stress. Oxidative stress is a key influencing factor for crop productivity in plants exposed to harsh conditions. In the defense mechanisms of plants against stress, phenolics serve an important antioxidant function. Cinnamate 4-hydroxylase (C4H) is the first hydroxylase in the plant phenolics biosynthesis pathway, and elucidating the molecular characteristics of this gene in R. glutinosa is essential for understanding the effect of tolerance to oxidative stress tolerance on improving yield. Using in vitro and in silico methods, a C4H gene, RgC4H, from R. glutinosa was isolated and characterized. RgC4H has 86.34-93.89% amino acid sequence identity with the equivalent protein in other plants and localized to the endoplasmic reticulum. An association between the RgC4H expression and total phenolics content observed in non-transgenic and transgenic R. glutinosa plants suggests that this gene is involved in the process of phenolics biosynthesis. Furthermore, the tolerance of R. glutinosa to drought, salinity and HO stresses was positively or negatively altered in plants with the overexpression or knockdown of RgC4H, respectively, as indicated by the analysis in some antioxidant physiological and molecular indices. Our study highlights the important role of RgC4H in the phenolics/phenylpropanoid pathway and reveals the involvement of phenolic-mediated regulation in oxidative stress tolerance in R. glutinosa.
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http://dx.doi.org/10.1007/s00299-020-02639-4DOI Listing
February 2021

Overexpression of RgPAL family genes involved in phenolic biosynthesis promotes the replanting disease development in Rehmannia glutinosa.

J Plant Physiol 2021 Feb 15;257:153339. Epub 2020 Dec 15.

College of Bioengineering, Henan University of Technology, Lianhua Street 100, Zhengzhou High-technology Zero, Henan Province, 450001, China. Electronic address:

Rehmannia glutinosa production is affected by the replanting disease, which involves autotoxic harm mediated by specific endogenous allelochemicals in root exudates. Many phenolics that act as allelochemical agents are mostly phenylpropanoid products of secondary metabolism in plants. Phenylalanine ammonia-lyase (PAL) is the first enzyme that catalyses the deamination of l-phenylalanine for entrance into the phenylpropanoid pathway. PAL family genes have been isolated and functionally characterized in many plant species. However, PAL family genes involved in phenolic biosynthesis remain largely uncharacterized in R. glutinosa. Here, we identified and characterized four PAL family genes (RgPAL2 to RgPAL5) in the species whose sequences exhibited highly conserved domains of PALs according to in silico analysis, implying their potential function in phenolic biosynthesis. Overexpression of RgPALs in R. glutinosa enhanced phenolic production, verifying that RgPAL family genes participate in phenolic biosynthesis pathways. Moreover, we found that the release of several allelopathic phenolics from the roots of RgPAL-overexpressing transgenic R. glutinosa increased, implying that the RgPALs positively promote their release. Importantly, under continuous monoculture stress, we found that the RgPAL transgenic plants exhibited more significant autotoxic harm than did non-transgenic (WT) plants by activating the phenolics/phenylpropanoid pathway, indicating that RgPAL family genes function as positive regulators of the replanting disease development in R. glutinosa. This study revealed that RgPAL family genes are involved in the biosynthesis and release of several phenolics and positively control the replanting disease development in R. glutinosa, laying a foundation for further clarification of the molecular mechanisms underlying the disease formation.
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http://dx.doi.org/10.1016/j.jplph.2020.153339DOI Listing
February 2021

GLP-1 preserves β cell function via improvement on islet insulin signaling in high fat diet feeding mice.

Neuropeptides 2021 Feb 21;85:102110. Epub 2020 Nov 21.

Department of Endocrinology, Renmin Hospital of Wuhan University, 430060, China. Electronic address:

Background: Numerous studies have shown that Glucagon like peptide-1 (GLP-1) treatment can protect β cell function, but the exact mechanism remains unclear. We hypothesized that GLP-1 may protect β cell function via its action on insulin signaling pathway.

Methods: Mice were fed with high fat diet (HFD, 20 weeks) in the presence or absence of GLP-1 receptor agonist (exenatide) treatment. The islet structure was demonstrated by HE staining. Immunofluorescence antibodies targeting insulin and glucagon were used to illustrate α and β cell distribution. The insulin and glucagon abundance was measured by ELISA using pancreatic homogenates. The molecules involved in insulin signaling pathway (IRc, IRS1, IRS2, mTOR) in islet were examined with immunohistochemistry and immunoblotting. The effect of IRS1 silencing on mTOR and apoptosis were examined on NIT cells(β cell line)with immunoblotting and flow cytometry.

Results: HE and immunofluorescence staining demonstrated that the normal structure of islet was deformed in HFD mice but preserved by exenatide. Insulin and glucagon contents were increased in islet and blood stream of HFD mice (HFD vs. Control, p<0.05) but resumed by exenatide. Meanwhile the expressions of IRc, IRS-1, mTOR from insulin signaling pathway and β cell apoptosis in the pancreas were significantly reduced (p<0.05) by HFD but reversed by exenatide.

Conclusion: Exenatide improved insulin signaling pathway that was suppressed by HFD in mice islet. Our results reveal a novel mechanism of the protective effects of GLP-1 on β cell function.
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http://dx.doi.org/10.1016/j.npep.2020.102110DOI Listing
February 2021

The effects of postmortem delay on mouse and human microglia gene expression.

Glia 2021 Apr 9;69(4):1053-1060. Epub 2020 Dec 9.

Department of Biomedical Sciences of Cells & Systems, Section Molecular Neurobiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Microglia are specialized macrophages of the central nervous system (CNS) and first to react to pathogens or injury. Over the last decade, transcriptional profiling of microglia significantly contributed to our understanding of their functions. In the case of human CNS samples, either potential CNS pathology in the case of surgery samples, or a postmortem delay (PMD) due to the time needed for tissue access and collection, are potential factors that affect gene expression profiles. To determine the effect of PMD on the microglia transcriptome, we first analyzed mouse microglia, where genotype, antemortem conditions and PMD can be controlled. Microglia were isolated from mice after different PMDs (0, 4, 6, 12, and 24 hr) using fluorescence-activated cell sorting (FACS). The number of viable microglia significantly decreased with increasing PMD, but even after a 12 hr PMD, high-quality RNA could be obtained. PMD had very limited effect on mouse microglia gene expression, only 50 genes were differentially expressed between different PMDs. These genes were related to mitochondrial, ribosomal, and protein binding functions. In human microglia transcriptomes we previously generated, 31 of the 50 PMD-associated mouse genes had human homologs, and their relative expression was also affected by PMD. This study provides a set of genes that shows relative expression changes in relation to PMD, both in mouse and human microglia. Although the gene expression changes detected are subtle, these genes need to be accounted for when analyzing microglia transcriptomes generated from samples with variable PMDs.
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http://dx.doi.org/10.1002/glia.23948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898322PMC
April 2021

Recognition of moyamoya disease and its hemorrhagic risk using deep learning algorithms: sourced from retrospective studies.

Neural Regen Res 2021 May;16(5):830-835

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

Although intracranial hemorrhage in moyamoya disease can occur repeatedly, predicting the disease is difficult. Deep learning algorithms developed in recent years provide a new angle for identifying hidden risk factors, evaluating the weight of different factors, and quantitatively evaluating the risk of intracranial hemorrhage in moyamoya disease. To investigate whether convolutional neural network algorithms can be used to recognize moyamoya disease and predict hemorrhagic episodes, we retrospectively selected 460 adult unilateral hemispheres with moyamoya vasculopathy as positive samples for diagnosis modeling, including 418 hemispheres with moyamoya disease and 42 hemispheres with moyamoya syndromes. Another 500 hemispheres with normal vessel appearance were selected as negative samples. We used deep residual neural network (ResNet-152) algorithms to extract features from raw data obtained from digital subtraction angiography of the internal carotid artery, then trained and validated the model. The accuracy, sensitivity, and specificity of the model in identifying unilateral moyamoya vasculopathy were 97.64 ± 0.87%, 96.55 ± 3.44%, and 98.29 ± 0.98%, respectively. The area under the receiver operating characteristic curve was 0.990. We used a combined multi-view conventional neural network algorithm to integrate age, sex, and hemorrhagic factors with features of the digital subtraction angiography. The accuracy of the model in predicting unilateral hemorrhagic risk was 90.69 ± 1.58% and the sensitivity and specificity were 94.12 ± 2.75% and 89.86 ± 3.64%, respectively. The deep learning algorithms we proposed were valuable and might assist in the automatic diagnosis of moyamoya disease and timely recognition of the risk for re-hemorrhage. This study was approved by the Institutional Review Board of Huashan Hospital, Fudan University, China (approved No. 2014-278) on January 12, 2015.
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http://dx.doi.org/10.4103/1673-5374.297085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178771PMC
May 2021

Novel Serotype of Epizootic Hemorrhagic Disease Virus, China.

Emerg Infect Dis 2020 12;26(12):3081-3083

In 2018, a strain of epizootic hemorrhagic disease virus (EHDV), named YNDH/V079/2018, was isolated from a sentinel calf in Mangshi County, Yunnan Province, China. Nucleotide sequencing and neutralization tests indicated that the virus belongs to a novel serotype of EHDV that had not been reported previously.
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http://dx.doi.org/10.3201/eid2612.191301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706924PMC
December 2020

Novel putative bluetongue virus serotype 29 isolated from inapparently infected goat in Xinjiang of China.

Transbound Emerg Dis 2021 Jul 6;68(4):2543-2555. Epub 2021 May 6.

Yunnan Tropical and Subtropical Animal Virus Diseases Laboratory, Yunnan Animal Science and Veterinary Institute, Kunming, Yunnan Province, China.

Bluetongue virus (BTV) is the 'type' species of the genus Orbivirus causing bluetongue (BT) in sheep, bovine and other ruminants. Twenty-four serotypes and several atypical serotypes of BTV were identified worldwide. In present study, a novel strain of BTV (V196/XJ/2014) was isolated from an asymptomatic sentinel goat in Yuli County, Xinjiang of China. Serotype identification of this isolate exhibited uniform negative results by serotype-specific conventional RT-PCR and real-time RT-PCR for BTV-1 to BTV-27, and virus neutralization tests using reference sera of BTV-1 to BTV-24. Genomic analysis showed V196/XJ/2014 grouped with atypical serotypes of BTV-25 to BTV-28, BTV-X/XJ1407, BTV-X/ITL2015 and BTV-Y/TUN2017, while segment 2 and VP2 protein of V196/XJ/2014 shared <63.4%/61.4% nucleic acids and amino acids sequence identities with other recognized BTV serotypes and its segment 2 formed a separate 'nucleotype' in phylogenetic tree. These results indicated V196/XJ/2014 does not belong to any reported serotypes of BTV. Further studies of infectivity and pathogenicity showed that goats infected with V196/XJ/2014 did not exhibit observed clinical symptoms, but high level of virus amplification and homologous neutralization antibodies were detected post-infection. Our studies suggested a novel putative serotype of BTV-29 was isolated in Xinjiang of China, which expands our knowledge about the diversity of BTV.
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http://dx.doi.org/10.1111/tbed.13927DOI Listing
July 2021

The covalent NLRP3-inflammasome inhibitor Oridonin relieves myocardial infarction induced myocardial fibrosis and cardiac remodeling in mice.

Int Immunopharmacol 2021 Jan 7;90:107133. Epub 2020 Nov 7.

Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang University, Nanchang 330006, Jiangxi Province, China. Electronic address:

Background: Myocardial infarction (MI) triggers a strong inflammatory response that is associated with myocardial fibrosis and cardiac remodeling. Interleukin (IL)-1β and IL-18 are key players in this response and are controlled by NLRP3-inflammatory bodies. Oridonin is a newly reported NLRP3 inhibitor with strong anti-inflammatory activity. We hypothesized that the covalent NLRP3 inhibitor Oridonin could reduce IL-1β and IL-18 expression and ameliorate myocardial fibrosis after myocardial infarction in mice, improve poor heart remodeling, and preserve heart function.

Methods: Male C57BL/6 mice were subjected to left coronary artery ligation to induce MI and then treated with Oridonin (1, 3, or 6 mg/kg), MCC950 (10 mg/kg), CY-09 (5 mg/kg) or saline three times a week for two weeks. Four weeks after MI, cardiac function and myocardial fibrosis were assessed. In addition, myocardial expressions of inflammatory factors and fibrotic markers were analyzed by western blot, immunofluorescence, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction.

Results: Oridonin treatment preserved left ventricular ejection fraction and fractional shortening, and markedly limited the myocardial infarct size in treated mice. The myocardial fibrosis was lower in the 1 mg/kg group (15.98 ± 1.64)%, 3 mg/kg group (17.39 ± 2.45)%, and 6 mg/kg group (16.76 ± 3.06)% compared to the control group (23.38 ± 1.65)%. Moreover, similar with the results of Oridonin, MCC950 and CY-09 also preserved cardiac function and reduced myocardial fibrosis. The expression levels of NLRP3, IL-1β and IL-18 were decreased in the Oridonin treatment group compared to non-treated group. In addition, myocardial macrophage and neutrophil influxes were attenuated in the Oridonin treated group.

Conclusions: The covalent NLRP3-inflammasome inhibitor Oridonin reduces myocardial fibrosis and preserves cardiac function in a mouse MI model, which indicates potential therapeutic effect of Oridonin on acute MI patients.
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http://dx.doi.org/10.1016/j.intimp.2020.107133DOI Listing
January 2021
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