Publications by authors named "Jingyu Liu"

256 Publications

Administration of Donor-Derived Nonexpanded Adipose Stromal Vascular Fraction Attenuates Ischemia-Reperfusion Injury in Donation After Cardiac Death Rat Renal Transplantation.

Transplant Proc 2021 Jul 12. Epub 2021 Jul 12.

Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China; Center of Renal Transplantation, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. Electronic address:

Donation after cardiac death (DCD) has become a potential source for transplantation organs. However, ischemia/reperfusion injury (IRI) induced by cardiac arrest has limited the use of DCD organs. Stromal vascular fraction (SVF) without the culturing step has been proposed as a safer and easier source for stem cell therapy, which has emerged as an attractive technology that could facilitate the recovery of renal function and structure from acute kidney injury induced by IRI after DCD renal transplantation. In this study, freshly isolated donor-derived SVF was identified and then delivered intra-arterially into the grafts in DCD rat renal transplantation. Administration of freshly isolated donor-derived SVF could significantly alleviate the IRI of renal grafts and enhance graft reparation by promoting graft cell proliferation and microvascularization in DCD renal transplantation. Moreover, results revealed that the oxidative stress in grafts was significantly alleviated with SVF treatment, and this might be attributed to the overexpression of antioxidative molecules including nuclear factor erythroid-related factor 2, superoxide dismutase-1, and heme oxygenase-1. In conclusion, our study demonstrated that the administration of freshly isolated donor-derived nonexpanded adipose SVF could attenuate IRI and protect the grafts after DCD rat renal transplantation.
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http://dx.doi.org/10.1016/j.transproceed.2021.05.012DOI Listing
July 2021

DNA methylation under the major depression pathway predicts pediatric quality of life four-month post-pediatric mild traumatic brain injury.

Clin Epigenetics 2021 Jul 12;13(1):140. Epub 2021 Jul 12.

Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, 55 Park Place NE, 18th Floor, Atlanta, GA, 30303, USA.

Background: Major depression has been recognized as the most commonly diagnosed psychiatric complication of mild traumatic brain injury (mTBI). Moreover, major depression is associated with poor outcomes following mTBI; however, the underlying biological mechanisms of this are largely unknown. Recently, genomic and epigenetic factors have been increasingly implicated in the recovery following TBI.

Results: This study leveraged DNA methylation within the major depression pathway, along with demographic and behavior measures (features used in the clinical model) to predict post-concussive symptom burden and quality of life four-month post-injury in a cohort of 110 pediatric mTBI patients and 87 age-matched healthy controls. The results demonstrated that including DNA methylation markers in the major depression pathway improved the prediction accuracy for quality of life but not persistent post-concussive symptom burden. Specifically, the prediction accuracy (i.e., the correlation between the predicted value and observed value) of quality of life was improved from 0.59 (p = 1.20 × 10) (clinical model) to 0.71 (p = 3.89 × 10); the identified cytosine-phosphate-guanine sites were mainly in the open sea regions and the mapped genes were related to TBI in several molecular studies. Moreover, depression symptoms were a strong predictor (with large weights) for both post-concussive symptom burden and pediatric quality of life.

Conclusion: This study emphasized that both molecular and behavioral manifestations of depression symptoms played a prominent role in predicting the recovery process following pediatric mTBI, suggesting the urgent need to further study TBI-caused depression symptoms for better recovery outcome.
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http://dx.doi.org/10.1186/s13148-021-01128-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274037PMC
July 2021

Conflict Data Fusion in a Multi-Agent System Premised on the Base Basic Probability Assignment and Evidence Distance.

Entropy (Basel) 2021 Jun 28;23(7). Epub 2021 Jun 28.

School of Big Data and Software Engineering, Chongqing University, Chongqing 401331, China.

The multi-agent information fusion (MAIF) system can alleviate the limitations of a single expert system in dealing with complex situations, as it allows multiple agents to cooperate in order to solve problems in complex environments. Dempster-Shafer (D-S) evidence theory has important applications in multi-source data fusion, pattern recognition, and other fields. However, the traditional Dempster combination rules may produce counterintuitive results when dealing with highly conflicting data. A conflict data fusion method in a multi-agent system based on the base basic probability assignment (bBPA) and evidence distance is proposed in this paper. Firstly, the new bBPA and reconstructed BPA are used to construct the initial belief degree of each agent. Then, the information volume of each evidence group is obtained by calculating the evidence distance so as to modify the reliability and obtain more reasonable evidence. Lastly, the final evidence is fused with the Dempster combination rule to obtain the result. Numerical examples show the effectiveness and availability of the proposed method, which improves the accuracy of the identification process of the MAIF system.
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http://dx.doi.org/10.3390/e23070820DOI Listing
June 2021

A dual band spin-selective transmission metasurface and its wavefront manipulation.

Nanoscale 2021 Jun;13(24):10898-10905

Key Laboratory of Opto-Electronics Information Technology (Tianjin University), Ministry of Education, School of Precision Instruments and Opto-Electronics Engineering, Tianjin University, Tianjin, 300072, China.

Chiral metasurfaces which can achieve different optical responses for left-handed and right-handed circularly polarized (CP) light have been proposed. Most of the research studies on chiral metasurfaces focus on improving circular dichroism (CD) and realizing dynamic manipulation of the chiro-optical response. However, there have only been a few reports on the multi-band chiro-optical response. Here, we propose an all-silicon chiral meta-atom which can realize spin-selective transmission in a dual band. In addition, a terahertz metasurface with spin-selective transmission through phase arrangement is designed by using chiral meta-atoms satisfying a gradient geometric phase. Under left-hand circularly polarized (LCP) incidence, the metasurface generates a focused right-hand circularly polarized (RCP) beam which is focused at a distance of 4.8 mm from the exit surface of the metasurface. Our work broadens the concept of metasurface design and may attract more researchers' attention on the applications of chiral metasurfaces.
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http://dx.doi.org/10.1039/d1nr02624kDOI Listing
June 2021

A high level of KLF12 causes folic acid-resistant neural tube defects by activating the Shh signalling pathway in mice.

Biol Reprod 2021 Jun 8. Epub 2021 Jun 8.

Reproductive Medicine Center, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu, People's Republic of China.

Although adequate periconceptional folic acid (FA) supplementation has reduced the occurrence of pregnancies affected by neural tube defects (NTDs), the mechanisms underlying FA-resistant NTDs are poorly understood, and thus NTDs still remain a global public health concern. A high level of Krüppel-like factor 12 (KLF12) exerts deleterious effects on heath in most cases, but evidence for its roles in development has not been published. We observed KLF12-overexpressing mice showed disturbed neural tube development. KLF12-overexpressing foetuses died in utero at approximately 10.5 days post coitus, with 100% presenting cranial NTDs. Neither FA nor formate promoted normal neural tube closure in mutant foetuses. The RNA-seq results showed that a high level of KLF12 caused NTDs in mice via overactivating the sonic hedgehog (Shh) signalling pathway, leading to the upregulation of patched 1, GLI-Krüppel family member GLI1, hedgehog-interacting protein, etc., while FA metabolism-related enzymes did not express differently. PF-5274857, an antagonist of the Shh signalling pathway, significantly promoted dorsolateral hinge point formation and partially rescued the NTDs. The regulatory hierarchy between a high level of KLF12 and FA-resistant NTDs might provide new insights into the diagnosis and treatment of unexplained NTDs in the future.
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http://dx.doi.org/10.1093/biolre/ioab111DOI Listing
June 2021

Disrupted dynamic functional network connectivity among cognitive control networks in the progression of Alzheimer's disease.

Brain Connect 2021 Jun 9. Epub 2021 Jun 9.

Georgia State University, 1373, Computer Science, Atlanta, Georgia, United States.

Background: Alzheimer's disease (AD) is the most common age-related dementia that promotes a decline in memory, thinking, and social skills. The initial stages of dementia can be associated with mild symptoms, and symptom progression to a more severe state is heterogeneous across patients. Recent work has demonstrated the potential for functional network mapping to assist in the prediction of symptomatic progression. However, this work has primarily used static functional connectivity (sFC) from rs-fMRI. Recently, dynamic functional connectivity (dFC) has been recognized as a powerful advance in functional connectivity methodology to differentiate brain network dynamics between healthy and diseased populations.

Methods: Group independent component analysis was applied to extract 17 components within the cognitive control network (CCN) from 1385 individuals across varying stages of AD symptomology. We estimated dFC among 17 components within the CCN, followed by clustering the dFCs into 3 recurring brain states, and then estimated a hidden Markov model and the occupancy rate for each subject. Then, we investigated the link between CCN dFC connectivity features with AD progression. Also, we investigated the link between sFC and AD progression and compared its results with dFC results.

Results: Progression of AD symptoms were associated with increases in connectivity within the middle frontal gyrus. Also, the very mild AD showed less connectivity within the inferior parietal lobule (in both sFC and dFC) and between this region with the rest of CCN (in dFC analysis). Also, we found within-middle frontal gyrus connectivity increases with AD progression in both sFC and dFC results. Finally, comparing with very mild AD, we found that the normal brain spends significantly more time in a state with lower within-middle frontal gyrus connectivity and higher connectivity between the hippocampus and the rest of CCN, highlighting the importance of assessing the dynamics of brain connectivity in this disease.
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http://dx.doi.org/10.1089/brain.2020.0847DOI Listing
June 2021

Genomic and Metabolomic Analysis of the Potato Common Scab Pathogen .

ACS Omega 2021 May 20;6(17):11474-11487. Epub 2021 Apr 20.

Department of Biology, Memorial University of Newfoundland, 232 Elizabeth Avenue, St. John's, NL A1B 3X9, Canada.

is a key causative agent of common scab disease, which causes significant economic losses to potato growers worldwide. This organism produces several phytotoxins that are known or suspected to contribute to host-pathogen interactions and disease development; however, the full metabolic potential of has not been previously investigated. In this study, we used a combined metabolomic and genomic approach to investigate the metabolites that are produced by . The genome sequence was analyzed using antiSMASH and DeepBGC to identify specialized metabolite biosynthetic gene clusters. Using untargeted liquid chromatography-coupled tandem mass spectrometry (LC-MS), the metabolic profile of was compared after cultivation on three different growth media. MS data were analyzed using Feature-Based Molecular Networking and hierarchical clustering in BioDendro. Metabolites were annotated by performing a Global Natural Products Social Molecular Networking (GNPS) spectral library search or using Network Annotation Propagation, SIRIUS, MetWork, or Competitive Fragmentation Modeling for Metabolite Identification. Using this approach, we were able to putatively identify new analogues of known metabolites as well as molecules that were not previously known to be produced by . To our knowledge, this study represents the first global analysis of specialized metabolites that are produced by this important plant pathogen.
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http://dx.doi.org/10.1021/acsomega.1c00526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153979PMC
May 2021

Metformin and Fibrosis: A Review of Existing Evidence and Mechanisms.

J Diabetes Res 2021 29;2021:6673525. Epub 2021 Apr 29.

Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China 646000.

Fibrosis is a physiological response to organ injury and is characterized by the excessive deposition of connective tissue components in an organ, which results in the disruption of physiological architecture and organ remodeling, ultimately leading to organ failure and death. Fibrosis in the lung, kidney, and liver accounts for a substantial proportion of the global burden of disability and mortality. To date, there are no effective therapeutic strategies for controlling fibrosis. A class of metabolically targeted chemicals, such as adenosine monophosphate-activated protein kinase (AMPK) activators and peroxisome proliferator-activated receptor (PPAR) agonists, shows strong potential in fighting fibrosis. Metformin, which is a potent AMPK activator and is the only recommended first-line drug for the treatment of type 2 diabetes, has emerged as a promising method of fibrosis reduction or reversion. In this review, we first summarize the key experimental and clinical studies that have specifically investigated the effects of metformin on organ fibrosis. Then, we discuss the mechanisms involved in mediating the antifibrotic effects of metformin in depth.
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http://dx.doi.org/10.1155/2021/6673525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102119PMC
April 2021

Influences of oxidation ability on precision in nitrogen isotope measurements of organic reference materials using elemental analysis-isotope ratio mass spectrometry.

Rapid Commun Mass Spectrom 2021 Jul;35(14):e9122

Frontiers Science Center for Deep Ocean Multispheres and Earth System, Key Lab of Marine Chemistry Theory and Technology, MOE and College of Marine Geosciences, Ocean University of China, Qingdao, 266100, China.

Rationale: The precision of the standard measurements of reference materials (RMs) is critical to normalize the raw δ N values of samples to the international scale. Because the measurement configuration is required to moderate the properties of both RMs and samples for obtaining an ideal measurement precision, it is important to determine the appropriate measurement configurations of RMs to achieve accurate nitrogen isotope compositions of samples. Therefore, it is critical to systematically examine RMs for optimizing the configurations and further improve the measurement precision.

Methods: Gas source isotope ratio mass spectrometry (IRMS) coupled with an online elemental analyzer (EA) equipped with a single-quartz reactor was performed to analyze the nitrogen isotope compositions. Some adjustments were made as follows: (a) as the in-house working standard, urea was used to investigate the influences of combustion through moderating the different oxygen injections (0-20 mL) and sample delay times (10-12 s) and optimize the combustion conditions to enhance oxidation ability; (b) CO from the sample gas stream was removed to prevent interferences between CO and N ; (c) international RMs, including USGS40 (l-glutamic), IAEA600 (caffeine), and soil standard (B2153) with a low organic content, were systematically analyzed under the optimized configurations, and the precisions of the δ N values were further examined.

Results: Our results showed that sufficient oxygen should be injected to improve the sample combustion when analyzing δ N in natural samples such as soil or marine sediment with low organic content. In addition, the measurement precision of δ N was affected by the tailing of the CO peak from the gas chromatography column into the subsequent sample measurement if the EA is equipped with a single-quartz reactor column. Our adjustments can produce an optimized repeatability and accuracy of the δ N value, especially for RMs with low organic content, and the uncertainty of the measurements is improved to be better than 0.1‰ under optimized configurations.

Conclusions: The analytical conditions such as the oxygen flow rate and injection time or sample introduction time into the EA need to be adjusted depending on the combustion conditions of the RMs and samples to obtain a reliable accuracy of measurement. We recommend that when analyzing δ N of natural samples such as soil or marine sediment samples with low organic content, more oxygen should be injected to improve the combustion of the samples. In addition, CO should be removed from the sample gas stream before being introduced into the isotope ratio mass spectrometer when the EA is equipped with a single-quartz reactor.
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http://dx.doi.org/10.1002/rcm.9122DOI Listing
July 2021

Alterations of frontal-temporal gray matter volume associate with clinical measures of older adults with COVID-19.

Neurobiol Stress 2021 May 13;14:100326. Epub 2021 Apr 13.

Department of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, USA.

COVID-19, the infectious disease caused by the most recently discovered severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global pandemic. It dramatically affects people's health and daily life. Neurological complications are increasingly documented for patients with COVID-19. However, the effect of COVID-19 on the brain is less studied, and existing quantitative neuroimaging analyses of COVID-19 were mainly based on the univariate voxel-based morphometry analysis (VBM) that requires corrections for a large number of tests for statistical significance, multivariate approaches that can reduce the number of tests to be corrected have not been applied to study COVID-19 effect on the brain yet. In this study, we leveraged source-based morphometry (SBM) analysis, a multivariate extension of VBM, to identify changes derived from computed tomography scans in covarying gray matter volume patterns underlying COVID-19 in 120 neurological patients (including 58 cases with COVID-19 and 62 patients without COVID-19 matched for age, gender and diseases). SBM identified that lower gray matter volume (GMV) in superior/medial/middle frontal gyri was significantly associated with a higher level of disability (modified Rankin Scale) at both discharge and six months follow-up phases even when controlling for cerebrovascular diseases. GMV in superior/medial/middle frontal gyri was also significantly reduced in patients receiving oxygen therapy compared to patients not receiving oxygen therapy. Patients with fever presented significant GMV reduction in inferior/middle temporal gyri and fusiform gyrus compared to patients without fever. Patients with agitation showed GMV reduction in superior/medial/middle frontal gyri compared to patients without agitation. Patients with COVID-19 showed no significant GMV differences from patients without COVID-19 in any brain region. Results suggest that COVID-19 may affect the frontal-temporal network in a secondary manner through fever or lack of oxygen.
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http://dx.doi.org/10.1016/j.ynstr.2021.100326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041745PMC
May 2021

Therapeutic potential of adipose-derived mesenchymal stem cell exosomes in tissue-engineered bladders.

J Tissue Eng 2021 Jan-Dec;12:20417314211001545. Epub 2021 Mar 31.

Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Mesenchymal stem cells (MSCs) are a therapeutic tool for tissue engineering. However, many studies have recently shown that the therapeutic effects of MSCs are mediated by paracrine signaling and their secretory factors rather than their multidirectional differentiation ability. Exosomes isolated from the conditioned medium of MSCs are considered the main intercellular communication medium between MSCs and their target cells. Exosomes have been utilized in a novel cell-free therapy strategy that has attracted much attention. In this study, we evaluated the effects of a new cell-free tissue-engineered bladder (bladder acellular matrix combined with adipose-derived mesenchymal stem cell exosomes (AMEs)) in vivo and in vitro to prove that AMEs promoted tissue regeneration and functional recovery in a rat bladder replacement model.
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http://dx.doi.org/10.1177/20417314211001545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020766PMC
March 2021

ATF3 deficiency impairs the proliferative-secretory phase transition and decidualization in RIF patients.

Cell Death Dis 2021 04 12;12(4):387. Epub 2021 Apr 12.

Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, People's Republic of China.

Decidualization is a complex process involving cellular proliferation and differentiation of the endometrial stroma and is required to establish and support pregnancy. Dysregulated decidualization has been reported to be a critical cause of recurrent implantation failure (RIF). In this study, we found that Activating transcription factor 3 (ATF3) expression was significantly downregulated in the endometrium of RIF patients. Knockdown of ATF3 in human endometrium stromal cells (hESCs) hampers decidualization, while overexpression could trigger the expression of decidual marker genes, and ameliorate the decidualization of hESCs from RIF patients. Mechanistically, ATF3 promotes decidualization by upregulating FOXO1 via suppressing miR-135b expression. In addition, the endometrium of RIF patients was hyperproliferative, while overexpression of ATF3 inhibited the proliferation of hESCs through CDKN1A. These data demonstrate the critical roles of endometrial ATF3 in regulating decidualization and proliferation, and dysregulation of ATF3 in the endometrium may be a novel cause of RIF and therefore represent a potential therapeutic target for RIF.
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http://dx.doi.org/10.1038/s41419-021-03679-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041902PMC
April 2021

Identification of Cucumber mosaic virus from Arisaema heterophyllum Blume in China.

Acta Virol 2021 ;65(1):97-100

Arisaema heterophyllum Blume is a valuable medicinal plant in the Araceae family. The dried tuber of A. heterophyllum is used in the traditional Chinese medicine, Rhizoma Arisaematis, which is used to treat convulsions, inflammation and cancer. In 2017, typical mosaic virus-like symptoms were observed in A. heterophyllum in Jilin province, China. To further identify the pathogens, we conducted RT-PCR using virus- and genus-specific primers to amplify partial genome sequences of Cucumber mosaic virus (CMV), Tobamovirus and Potyvirus, respectively. The CMV primers showed specific amplification, but the Tobamovirus and Potyvirus primers did not. We further cloned and sequenced the 2b, MP and CP genes of the CMV-Ah isolate. Phylogenetic analysis showed the CMV-Ah isolate belonged to subgroup IB. To our knowledge, this is the first report of CMV infecting A. heterophyllum in China. Keywords: Cucumber mosaic virus; Arisaema heterophyllum Blume; subgroup IB; phylogenetic analysis.
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http://dx.doi.org/10.4149/av_2021_112DOI Listing
April 2021

A Structure-Aware Relation Network for Thoracic Diseases Detection and Segmentation.

IEEE Trans Med Imaging 2021 Apr 5;PP. Epub 2021 Apr 5.

Instance level detection and segmentation of thoracic diseases or abnormalities are crucial for automatic diagnosis in chest X-ray images. Leveraging on constant structure and disease relations extracted from domain knowledge, we propose a structure-aware relation network (SAR-Net) extending Mask R-CNN. The SAR-Net consists of three relation modules: 1. the anatomical structure relation module encoding spatial relations between diseases and anatomical parts. 2. the contextual relation module aggregating clues based on query-key pair of disease RoI and lung fields. 3. the disease relation module propagating co-occurrence and causal relations into disease proposals. Towards making a practical system, we also provide ChestX-Det, a chest X-Ray dataset with instance-level annotations (boxes and masks). ChestX-Det is a subset of the public dataset NIH ChestX-ray14. It contains ~ 3500 images of 13 common disease categories labeled by three board-certified radiologists. We evaluate our SAR-Net on it and another dataset DR-Private. Experimental results show that it can enhance the strong baseline of Mask R-CNN with significant improvements. The ChestX-Det is released at https://github.com/Deepwise-AILab/ChestX-Det-Dataset.
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http://dx.doi.org/10.1109/TMI.2021.3070847DOI Listing
April 2021

sp. nov., a New Ectomycorrhizal Fungus from Mediterranean Croatia Revealed by Morphology and Multilocus Phylogenetic Analysis.

J Fungi (Basel) 2021 Mar 10;7(3). Epub 2021 Mar 10.

Laboratory for Biological Diversity, Ruđer Bošković Institute, Bijenička cesta 54, HR-10000 Zagreb, Croatia.

A new ectomycorrhizal species was discovered during the first survey of fungal diversity at Brijuni National Park (Croatia), which consists of 14 islands and islets. The National Park is located in the Mediterranean Biogeographical Region, a prominent climate change hot-spot. sp. nov., from sect. (Agaricales, Inocybaceae), is described based on morphology and multilocus phylogenetic data. The holotype collection was found at the edge between grassland and forest with a few planted trees, on Veli Brijun Island, the largest island of the archipelago. It is easily recognized by a conspicuous orange to orange-red-brown membranaceous surface layer located at or just above the basal part of the stipe. Other distinctive features of are the medium brown, radially fibrillose to rimose pileus; pale to medium brown stipe with fugacious cortina; relatively small, amygdaliform to phaseoliform, and smooth basidiospores, measuring ca. 6.5-9 × 4-5.5 µm; thick-walled, utriform, lageniform or fusiform pleurocystidia (lamprocystidia) with crystals and mostly not yellowing in alkaline solutions; cheilocystidia of two types (lamprocystidia and leptocystidia); and the presence of abundant caulocystidia only in the upper 2-3 mm of the stipe. Phylogenetic reconstruction of a concatenated dataset of the internal transcribed spacer region (ITS), the nuclear 28S rRNA gene (nrLSU), and the second largest subunit of RNA polymerase II () resolved and as sister species.
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http://dx.doi.org/10.3390/jof7030199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000951PMC
March 2021

Discrepancies of polygenic effects on symptom dimensions between adolescents and adults with ADHD.

Psychiatry Res Neuroimaging 2021 05 20;311:111282. Epub 2021 Mar 20.

Department of Psychology, Georgia State University, United States; Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology and Emory University, USA; Neuroscience Institute, Georgia State University, USA.

A significant proportion of individuals with attention-deficit/hyperactivity disorder (ADHD) show persistence into adulthood. The genetic and neural correlates of ADHD in adolescents versus adults remain poorly characterized. We investigated ADHD polygenic risk score (PRS) in relation to previously identified gray matter (GM) patterns, neurocognitive, and symptom findings in the same ADHD sample (462 adolescents & 422 adults from the NeuroIMAGE and IMpACT cohorts). Significant effects of ADHD PRS were found on hyperactivity and impulsivity symptoms in adolescents, hyperactivity symptom in adults, but not GM volume components. A distinct PRS effect between adolescents and adults on individual ADHD symptoms is suggested.
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http://dx.doi.org/10.1016/j.pscychresns.2021.111282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058322PMC
May 2021

Gray matter networks associated with attention and working memory deficit in ADHD across adolescence and adulthood.

Transl Psychiatry 2021 03 25;11(1):184. Epub 2021 Mar 25.

Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University Georgia Institute of Technology and Emory University, Atlanta, GA, USA.

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neuropsychiatric disorder and may persist into adulthood. Working memory and attention deficits have been reported to persist from childhood to adulthood. How neuronal underpinnings of deficits differ across adolescence and adulthood is not clear. In this study, we investigated gray matter of two cohorts, 486 adults and 508 adolescents, each including participants from ADHD and healthy controls families. Two cohorts both presented significant attention and working memory deficits in individuals with ADHD. Independent component analysis was applied to the gray matter of each cohort, separately, to extract cohort-inherent networks. Then, we identified gray matter networks associated with inattention or working memory in each cohort, and projected them onto the other cohort for comparison. Two components in the inferior, middle/superior frontal regions identified in adults and one component in the insula and inferior frontal region identified in adolescents were significantly associated with working memory in both cohorts. One component in bilateral cerebellar tonsil and culmen identified in adults and one component in left cerebellar region identified in adolescents were significantly associated with inattention in both cohorts. All these components presented a significant or nominal level of gray matter reduction for ADHD participants in adolescents, but only one showed nominal reduction in adults. Our findings suggest although the gray matter reduction of these regions may not be indicative of persistency of ADHD, their persistent associations with inattention or working memory indicate an important role of these regions in the mechanism of persistence or remission of the disorder.
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http://dx.doi.org/10.1038/s41398-021-01301-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994833PMC
March 2021

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Transl Psychiatry 2021 03 22;11(1):182. Epub 2021 Mar 22.

Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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http://dx.doi.org/10.1038/s41398-021-01213-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985307PMC
March 2021

CD146 is a Novel ANGPTL2 Receptor that Promotes Obesity by Manipulating Lipid Metabolism and Energy Expenditure.

Adv Sci (Weinh) 2021 Mar 27;8(6):2004032. Epub 2021 Jan 27.

Key Laboratory of RNA Biology Key Laboratory of Protein and Peptide Pharmaceuticals Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China.

Obesity and its related complications pose an increasing threat to human health; however, targetable obesity-related membrane receptors are not yet elucidated. Here, the membrane receptor CD146 is demonstrated to play an essential role in obesity. In particular, CD146 acts as a new adipose receptor for angiopoietin-like protein 2 (ANGPTL2), which is thought to act on endothelial cells to activate adipose inflammation. ANGPTL2 binds to CD146 to activate cAMP response element-binding protein (CREB), which then upregulates CD146 during adipogenesis and adipose inflammation. CD146 is present in preadipocytes and mature adipocytes, where it is mediated by its ligands ANGPTL2 and galectin-1. In preadipocytes, CD146 ablation suppresses adipogenesis, whereas the loss of CD146 in mature adipocytes suppresses lipid accumulation and enhances energy expenditure. Moreover, anti-CD146 antibodies inhibit obesity by disrupting the interactions between CD146 and its ligands. Together, these findings demonstrate that ANGPTL2 directly affects adipocytes via CD146 to promote obesity, suggesting that CD146 can be a potential target for treating obesity.
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http://dx.doi.org/10.1002/advs.202004032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967059PMC
March 2021

Effects of neutron radiation on Nrf2-regulated antioxidant defense systems in rat lens.

Exp Ther Med 2021 Apr 8;21(4):334. Epub 2021 Feb 8.

Department of Ophthalmology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.

Accumulating evidence suggests that ionizing radiation (IR)-induced cataract may be associated with oxidative stress. Nuclear factor erythroid 2-related factor 2 (Nrf2) serves as a master regulator of the antioxidant defense system against oxidative stress. The present study aimed to investigate the effects of different doses of neutron radiation on the Nrf2-reegulated antioxidant defense system in rat lens and assess the status of oxidative stress. A total of 24 SD rats were randomly divided into the following four groups: i) Control group; iis) 0.4 Sv group; iii) 1.2 Sv group; and iv) 3.6 Sv group. The rats were sacrificed 7 days after radiation and lenses were dissected for histological, biochemical (malondialdehyde, glutathione and superoxide dismutase) and western blot (Nrf2, glutamate-cysteine ligase catalytic subunit and heme oxygenase 1) analyses. The morphological features of the lenses remained intact in the 0.4 Sv, 1.2 Sv and control groups, whilst the lenses in the 3.6 Sv group exhibited injuries. Results from the TUNEL assay demonstrated apparent apoptosis in lens epithelial cells following 3.6 Sv neutron radiation whereas sparse apoptosis was observed following 0.4 Sv and 1.2 Sv radiation. Malondialdehyde levels were reduced in the 0.4 Sv and 1.2 Sv groups but increased in the 3.6 Sv group, compared with those in the control group. Conversely, glutathione expression and the activity of superoxide dismutase were higher in the 0.4 Sv and 1.2 Sv groups, but lower in the 3.6 Sv group, compared with those in the control group. In addition, the total and nuclear protein levels of Nrf2 were increased following neutron radiation compared with those in the control group, though the Nrf2 protein levels decreased in the 3.6 Sv group compared with those in the 1.2 Sv group. The levels of glutamate-cysteine ligase catalytic subunit and heme oxygenase 1, downstream antioxidant enzymes of Nrf2, demonstrated the same profile as that in Nrf2. Taken together, the results of the present study suggest that neutron radiation affects Nrf2-regulated antioxidant systems in a two-stage process. Namely, the induction phase for low-dose radiation and regression phase for high-dose radiation. Therefore, it was hypothesized that activation and enhancement of the Nrf2-regulated antioxidant system may be useful in preventing or delaying IR-induced cataract, which may be extended even for other diseases associated with oxidative stress.
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http://dx.doi.org/10.3892/etm.2021.9765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903385PMC
April 2021

Sparse deep neural networks on imaging genetics for schizophrenia case-control classification.

Hum Brain Mapp 2021 Jun 16;42(8):2556-2568. Epub 2021 Mar 16.

Department of Computer Science, Georgia State University, Atlanta, Georgia, USA.

Deep learning methods hold strong promise for identifying biomarkers for clinical application. However, current approaches for psychiatric classification or prediction do not allow direct interpretation of original features. In the present study, we introduce a sparse deep neural network (DNN) approach to identify sparse and interpretable features for schizophrenia (SZ) case-control classification. An L -norm regularization is implemented on the input layer of the network for sparse feature selection, which can later be interpreted based on importance weights. We applied the proposed approach on a large multi-study cohort with gray matter volume (GMV) and single nucleotide polymorphism (SNP) data for SZ classification. A total of 634 individuals served as training samples, and the classification model was evaluated for generalizability on three independent datasets of different scanning protocols (N = 394, 255, and 160, respectively). We examined the classification power of pure GMV features, as well as combined GMV and SNP features. Empirical experiments demonstrated that sparse DNN slightly outperformed independent component analysis + support vector machine (ICA + SVM) framework, and more effectively fused GMV and SNP features for SZ discrimination, with an average error rate of 28.98% on external data. The importance weights suggested that the DNN model prioritized to select frontal and superior temporal gyrus for SZ classification with high sparsity, with parietal regions further included with lower sparsity, echoing previous literature. The results validate the application of the proposed approach to SZ classification, and promise extended utility on other data modalities and traits which ultimately may result in clinically useful tools.
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http://dx.doi.org/10.1002/hbm.25387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090768PMC
June 2021

Discrepancy Between Multi-Biomarker Disease Activity and Clinical Disease Activity Scores in Patients With Persistently Active Rheumatoid Arthritis.

Arthritis Care Res (Hoboken) 2021 Feb 28. Epub 2021 Feb 28.

David Geffen School of Medicine, Division of Rheumatology, University of California, Los Angeles, California, United States.

Objective: Responsive assessment of disease activity in patients with rheumatoid arthritis (RA) is necessary to evaluate therapeutic efficacy and guide treatment. We compared the utility of the multi-biomarker disease activity (MBDA) score in assessing RA disease activity with that of the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) and the Clinical Disease Activity Index (CDAI) in a multicenter, randomized, placebo-controlled trial of repository corticotropin injection (RCI) in patients with persistently active RA.

Methods: Patients received 80 U of RCI twice weekly during a 12-week open-label period; those who achieved low disease activity at week 12 were randomly assigned to receive either 80 U of RCI or placebo twice weekly during a 12-week double-blind period. Changes in disease activity (measured by DAS28-ESR, CDAI, and MBDA) and correlations between MBDA scores and both DAS28-ESR and CDAI scores were assessed.

Results: Changes from baseline in DAS28-ESR and CDAI scores suggested that RCI therapy led to clinically meaningful improvements in disease activity, but improvements from baseline in MBDA scores were below the minimally important difference threshold. For the DAS28-ESR and CDAI, correlations with total MBDA and individual component scores were generally low (r≤0.3), occasionally moderate (r>0.3 but <0.5).

Conclusion: Our results suggest overall MBDA scores are not sufficiently responsive for assessing RA disease activity after RCI therapy. These findings are consistent with those seen with other RA drugs and, although they are from a clinical trial, suggest the MBDA should not be a preferred disease activity measure in clinical practice.
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http://dx.doi.org/10.1002/acr.24583DOI Listing
February 2021

Acutissimalignan B from traditional herbal medicine Daphne kiusiana var. atrocaulis (Rehd.) F. Maekawa inhibits neuroinflammation via NF-κB Signaling pathway.

Phytomedicine 2021 Apr 11;84:153508. Epub 2021 Feb 11.

College of Life and Health Sciences, Northeastern University, Shenyang 110004, P.R.. Electronic address:

Background: Emerging evidence indicates the important role of herbal medicine for neuroinflammation, which is closely associated with neurodegenerative diseases.

Objective: To clarify the characteristics and primary mechanisms of action of the traditional herbal medicine Daphne kiusiana var. atrocaulis (Rehd.) F. Maekawa in neuroinflammation by phytochemistry and bioassays using both in vitro and in vivo assays.

Methods: The chemical composition of D. kiusiana var. atrocaulis was clarified using multiple chromatography technologies and spectroscopic analysis. The anti-neuroinflammatory effects of the identified components were evaluated in LPS-induced BV-2 cells by monitoring the production of nitric oxide. C57BL/6 mice were used to construct a neuroinflammatory model by injecting LPS into the lateral ventricle of the brain. The most promising component was evaluated in vivo by measuring the number of Iba-1 cells and expression of inflammatory factors. Furthermore, the anti-neuroinflammatory mechanism involved in the activation of the NF-κB pathway was investigated using western blot and immunofluorescence.

Results: Thirty-two constituents (1-32), including five new compounds, were successfully identified from D. kiusiana var. atrocaulis. Compounds 3, 5, 12-15, and 20 (IC values from 5.41 to 57.27 μM) could considerably inhibit the LPS-induced production of NO in BV-2 cells, displaying stronger anti-neuroinflammatory activities than that of minocycline (IC = 67.08 μM). The concentration of the most potential compound 13 (IC 5.41 μM) was 5.4% of the ethyl acetate fraction. Acutissimalignan B (13) could reduce the mRNA expression of iNOs, TNF-α, IL-1β, and IL-6, inhibit the phosphorylation of IκBα, and inhibit the nuclear translocation of NK-κB p65 in BV-2 cells induced by LPS. Moreover, in the LPS-induced mouse model, compound 13 was found to exert anti-neuroinflammatory activity by attenuating the activation of microglia in the cortex and hippocampus, repressing the phosphorylation of IκBα, inhibiting the nuclear translocation of NK-κB p65, and decreasing the mRNA expression of iNOs, TNF-α, IL-1β, and IL-6 in the cortex.

Conclusion: We found that D. kiusiana var. atrocaulis had an inhibitory activity on neuroinflammation. In addition, the main active component (-)-acutissimalignan B (13) showed anti-neuroinflammatory effects in both in vivo and in vitro assays. Its mechanism of action may be associated with the inhibition of the NF-κB signaling pathway. Our current findings provide new information on D. kiusiana var. atrocaulis in the treatment of neuroinflammation.
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http://dx.doi.org/10.1016/j.phymed.2021.153508DOI Listing
April 2021

Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs.

Hum Brain Mapp 2021 Feb 21. Epub 2021 Feb 21.

Center for Neuroimaging, Genetics and Genomics, School of Psychology, NUI Galway, Galway, Ireland.

The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This "genotype-first" approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.
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http://dx.doi.org/10.1002/hbm.25354DOI Listing
February 2021

Efficient transfection and long-term stability of rno-miRNA-26a-5p for osteogenic differentiation by large pore sized mesoporous silica nanoparticles.

J Mater Chem B 2021 03;9(9):2275-2284

School of Dentistry, The University of Queensland, Herston QLD 4006, Australia.

MicroRNA (miRNA) based therapy for bone repair has shown promising results for regulating stem cell proliferation and differentiation, an efficient and stable vector for delivery of microRNA delivery is needed. The present study explored the stability and functionality of lyophilized mesoporous silica nanoparticles with core-cone structure and coated with polyethylenimine (MSN-CC-PEI) as a system for delivering Rattus norvegicus (rno)-miRNA-26a-5p into rat marrow mesenchymal cells (rBMSCs) to promote their osteogenic differentiation. We assessed the cellular uptake and transfection efficiency of nanoparticles loaded with labelled miRNA using confocal laser scanning microscopy and flow cytometry, and the cell viability using the MTT assay. The expression levels of osteogenic genes after one and two weeks were analysed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Extracellular matrix deposition and mineralization at 3 weeks were evaluated using Picro Sirius red and Alizarin red staining. We also assessed the performance of the delivery system after long term storage, by freeze drying [email protected] with 5% trehalose and keeping them at -30 °C for 3 and 6 months. Osteogenic differentiation, matrix deposition, and mineralization were all significantly increased by rno-miRNA-26a-5p. In addition, this enhancement was not significantly altered by lyophilization and storage. Overall, these findings support the concept of MSN-CC-PEI as a delivery system for gene therapy. The complex of [email protected] could efficiently transfect rBMSCs and enhance their osteogenic differentiation. In addition, the lyophilized complexes remain functional after 6 months of storage.
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http://dx.doi.org/10.1039/d0tb02756aDOI Listing
March 2021

Alzheimer's Disease Projection From Normal to Mild Dementia Reflected in Functional Network Connectivity: A Longitudinal Study.

Front Neural Circuits 2020 21;14:593263. Epub 2021 Jan 21.

Wallace H. Coulter Department of Biomedical Engineering at Georgia Institute of Technology and Emory University, Atlanta, GA, United States.

Background: Alzheimer's disease (AD) is the most common age-related problem and progresses in different stages, including mild cognitive impairment (early stage), mild dementia (middle-stage), and severe dementia (late-stage). Recent studies showed changes in functional network connectivity obtained from resting-state functional magnetic resonance imaging (rs-fMRI) during the transition from healthy aging to AD. By assuming that the brain interaction is static during the scanning time, most prior studies are focused on static functional or functional network connectivity (sFNC). Dynamic functional network connectivity (dFNC) explores temporal patterns of functional connectivity and provides additional information to its static counterpart.

Method: We used longitudinal rs-fMRI from 1385 scans (from 910 subjects) at different stages of AD (from normal to very mild AD or vmAD). We used group-independent component analysis (group-ICA) and extracted 53 maximally independent components (ICs) for the whole brain. Next, we used a sliding-window approach to estimate dFNC from the extracted 53 ICs, then group them into 3 different brain states using a clustering method. Then, we estimated a hidden Markov model (HMM) and the occupancy rate (OCR) for each subject. Finally, we investigated the link between the clinical rate of each subject with state-specific FNC, OCR, and HMM.

Results: All states showed significant disruption during progression normal brain to vmAD one. Specifically, we found that subcortical network, auditory network, visual network, sensorimotor network, and cerebellar network connectivity decrease in vmAD compared with those of a healthy brain. We also found reorganized patterns (i.e., both increases and decreases) in the cognitive control network and default mode network connectivity by progression from normal to mild dementia. Similarly, we found a reorganized pattern of between-network connectivity when the brain transits from normal to mild dementia. However, the connectivity between visual and sensorimotor network connectivity decreases in vmAD compared with that of a healthy brain. Finally, we found a normal brain spends more time in a state with higher connectivity between visual and sensorimotor networks.

Conclusion: Our results showed the temporal and spatial pattern of whole-brain FNC differentiates AD form healthy control and suggested substantial disruptions across multiple dynamic states. In more detail, our results suggested that the sensory network is affected more than other brain network, and default mode network is one of the last brain networks get affected by AD In addition, abnormal patterns of whole-brain dFNC were identified in the early stage of AD, and some abnormalities were correlated with the clinical score.
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http://dx.doi.org/10.3389/fncir.2020.593263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859281PMC
January 2021

Formation of an aminovinyl-cysteine residue in thioviridamides occurs through a path independent of known lanthionine synthetase activity.

Cell Chem Biol 2021 May 20;28(5):675-685.e5. Epub 2021 Jan 20.

State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China; Huzhou Center of Bio-Synthetic Innovation, 1366 Hongfeng Road, Huzhou 313000, China. Electronic address:

2-Aminovinyl-cysteine (AviCys) is a thioether amino acid shared by a variety of ribosomally synthesized and posttranslationally modified peptides (RiPPs). Based on investigations into the biosynthesis of thioviridamide RiPPs in Streptomyces sp. NRRL S-87, we here report a path for the formation of this unusual thioether residue. This path relies on four dedicated proteins: phosphotransferase TvaC, Lyase TvaD, kinase homolog TvaE, and LanD-like flavoprotein TvaF. TvaE plays a critical role in effective AviCys formation. During the posttranslational modifications of the precursor peptide, it works with TvaF to form a minimum AviCys synthetase complex, which follows the combined activity of TvaCD for Thr dehydration and catalyzes Cys oxidative decarboxylation and subsequent Michael addition of the resulting enethiol nucleophile onto the newly formed dehydroamino acid residue for cyclization. With TvaE, TvaF activity for Cys processing can be coordinated with TvaCD activity for minimizing competitive or unexpected spontaneous reactions and forming AviCys effectively.
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http://dx.doi.org/10.1016/j.chembiol.2020.12.016DOI Listing
May 2021

Natural potential neuroinflammatory inhibitors from Stephania epigaea H.S. Lo.

Bioorg Chem 2021 02 29;107:104597. Epub 2020 Dec 29.

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, People's Republic of China. Electronic address:

Stephania epigaea H. S. Lo is a folk medicine widely distributed in the south of China, especially in Yunnan and Guangxi province. An in vitro anti-neuroinflammatory study showed that total alkaloids of it can potently inhibit LPS-induced NO releasing of BV2 cells with an IC value of 10.05 ± 2.03 μg/mL (minocycline as the positive drug, IC 15.49 ± 2.14 μM). The phytochemical investigation of the total alkaloids afforded three new phenanthrene (1-3), two lactams (4a, 4b), and nine aporphine derivatives (5-13). The final structure of 1 was identified by computer-assisted structure elucidation (ACD/Structure Elucidator software and the C NMR calculation with GIAO method) due to many possibilities of the substituent pattern. All isolates were evaluated for their anti-neuroinflammatory effects, and as a result, 5, 8, 10, and 11 exhibited stronger inhibitory activities than the minocycline. The results suggested S. epigaea could provide potential therapeutic agents for neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.bioorg.2020.104597DOI Listing
February 2021

A Joint Analysis of Multi-Paradigm fMRI Data With Its Application to Cognitive Study.

IEEE Trans Med Imaging 2021 03 2;40(3):951-962. Epub 2021 Mar 2.

With the development of neuroimaging techniques, a growing amount of multi-modal brain imaging data are collected, facilitating comprehensive study of the brain. In this paper, we jointly analyzed functional magnetic resonance imaging (fMRI) collected under different paradigms in order to understand cognitive behaviors of an individual. To this end, we proposed a novel multi-view learning algorithm called structure-enforced collaborative regression (SCoRe) to extract co-expressed discriminative brain regions under the guidance of anatomical structure of the brain. An advantage of SCoRe over its predecessor collaborative regression (CoRe) lies in its incorporation of group structures in the brain imaging data, which makes the model biologically more meaningful. Results from real data analysis has confirmed that by incorporating prior knowledge of brain structure, SCoRe can deliver better prediction performance and is less sensitive to hyper-parameters than CoRe. After validation with simulation experiments, we applied SCoRe to fMRI data collected from the Philadelphia Neurodevelopmental Cohort and adopted the scores from the wide range achievement test (WRAT) to evaluate an individual's cognitive skills. We located 14 relevant brain regions that can efficiently predict WRAT scores and these brain regions were further confirmed by other independent studies.
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http://dx.doi.org/10.1109/TMI.2020.3042786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925383PMC
March 2021

Pterostilbene Alleviates Aβ -Induced Cognitive Dysfunction via Inhibition of Oxidative Stress by Activating Nrf2 Signaling Pathway.

Mol Nutr Food Res 2021 01 16;65(2):e2000711. Epub 2020 Dec 16.

College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.

Scope: In the present study, effect of pterostilbene on β-amyloid 1-42 (Aβ ) induced cognitive impairment in mice is investigated and explored its possible mechanism of action.

Methods And Results: The behavior results show that pterostilbene alleviated Aβ -induces cognitive dysfunction assessed using the Y-maze test, novel object recognition task, Morris water maze test, and passive avoidance test. Pterostilbene alleviates neuron loss and accumulation of reactive oxygen species in Aβ treated mouse brain. Additionally, pterostilbene promotes nuclear factor-E2 p45-related factor 2 (Nrf2) nuclear translocation and enhance the transcription and expression of antioxidant genes such as heme oxygenase-1 and superoxide dismutase both in vivo and in vitro. Nrf2 inhibitor ML385 reverses the antioxidant function of pterostilbene in SH-SY5Y cells. Nrf2 is the master regulator of oxidative homeostasis and can be activated by substrate adaptor sequestosome-1 (also named p62). Pterostilbene promotes the binding of Kelch-like ECH-associated protein 1 and p62, which enhanced activation of Nrf2.

Conclusion: The present study reports that pterostilbene alleviated Aβ -induces cognitive dysfunction in mice. The mechanism of pterostilbene can be associated to the inhibition of oxidative stress through the Nrf2 signaling pathway.
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http://dx.doi.org/10.1002/mnfr.202000711DOI Listing
January 2021