Publications by authors named "Ya Guo"

131 Publications

Abnormal brain functional network dynamics in obsessive-compulsive disorder patients and their unaffected first-degree relatives.

Hum Brain Mapp 2021 Jun 5. Epub 2021 Jun 5.

Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, China; School of Psychology, Center for Studies of Psychological Application, and Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, China.

We utilized dynamic functional network connectivity (dFNC) analysis to compare participants with obsessive-compulsive disorder (OCD) with their unaffected first-degree relative (UFDR) and healthy controls (HC). Resting state fMRI was performed on 46 OCD, 24 UFDR, and 49 HCs, along with clinical assessments. dFNC analyses revealed two distinct connectivity states: a less frequent, integrated state characterized by the predominance of between-network connections (State I), and a more frequent, segregated state with strong within-network connections (State II). OCD patients spent more time in State II and less time in State I than HC, as measured by fractional windows and mean dwell time. Time in each state for the UFDR were intermediate between OCD patients and HC. Within the OCD group, fractional windows of time spent in State I was positively correlated with OCD symptoms (as measured by the obsessive compulsive inventory-revised [OCI-R], r = .343, p<.05, FDR correction) and time in State II was negatively correlated with symptoms (r = -.343, p<.05, FDR correction). Within each state we also examined connectivity within and between established intrinsic connectivity networks, and found that UFDR were similar to the OCD group in State I, but more similar to the HC groups in State II. The similarities between OCD and UFDR groups in temporal properties and State I connectivity indicate that these features may reflect the endophenotype for OCD. These results indicate that the temporal dynamics of functional connectivity could be a useful biomarker to identify those at risk.
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http://dx.doi.org/10.1002/hbm.25555DOI Listing
June 2021

Effects of antibiotics stress on growth variables, ultrastructure, and metabolite pattern of Brassica rapa ssp. chinensis.

Sci Total Environ 2021 Jul 11;778:146333. Epub 2021 Mar 11.

Key Laboratory of Advanced Process Control for Light Industry, Ministry of Education, Jiangnan University, Wuxi 214122, China; University of Missouri, Columbia, MO 65211, USA. Electronic address:

Antibiotics frequently contaminate agricultural fields and through plant uptake enter into the food chain. This study aimed to explore the effects of antibiotics; tetracycline (TC), oxytetracycline (OTC) and norfloxacin (NF) on the growth, cell ultrastructure, and metabolite pattern of Brassica rapa ssp. chinensis. Oxytetracycline accumulated more than other antibiotics followed by TC and NF. Plant growth, chlorophyll fluorescence, and antioxidant activities were negatively affected under all antibiotic treatments. Ultrastructural investigation of mesophyll of leaves performed by transmission electron microscopy indicated that antibiotic stress caused the changes in thylakoid orientation, number of plastoglobuli, and starch grains. Identification of functional groups through Fourier transform infrared analysis indicated that carboxyl group, carbonate and ammonium ions are involved in the adsorption of antibiotics. The metabolic profiling of B. rapa leaves demonstrated that all of the antibiotics treatments distorted phenylalanine, tyrosine and tryptophan biosynthesis, d-glutamine and d-glutamate metabolism, alanine, aspartate and glutamate metabolism, phenylalanine metabolism and TCA cycle. Metabolic alterations as a result of antibiotics stress provide insights of metabolites that affect the physiological changes attributed to antibiotic stress. These results will improve the understanding of antibiotic contamination effects on plants.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146333DOI Listing
July 2021

Neuronal genes deregulated in Cornelia de Lange Syndrome respond to removal and re-expression of cohesin.

Nat Commun 2021 05 18;12(1):2919. Epub 2021 May 18.

Lymphocyte Development Group, Epigenetics Section, MRC London Institute of Medical Sciences, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK.

Cornelia de Lange Syndrome (CdLS) is a human developmental disorder caused by mutations that compromise the function of cohesin, a major regulator of 3D genome organization. Cognitive impairment is a universal and as yet unexplained feature of CdLS. We characterize the transcriptional profile of cortical neurons from CdLS patients and find deregulation of hundreds of genes enriched for neuronal functions related to synaptic transmission, signalling processes, learning and behaviour. Inducible proteolytic cleavage of cohesin disrupts 3D genome organization and transcriptional control in post-mitotic cortical mouse neurons, demonstrating that cohesin is continuously required for neuronal gene expression. The genes affected by acute depletion of cohesin belong to similar gene ontology classes and show significant numerical overlap with genes deregulated in CdLS. Interestingly, reconstitution of cohesin function largely rescues altered gene expression, including the expression of genes deregulated in CdLS.
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http://dx.doi.org/10.1038/s41467-021-23141-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131595PMC
May 2021

Evaluating the Impact of Summer Drought on Vegetation Growth Using Space-Based Solar-Induced Chlorophyll Fluorescence Across Extensive Spatial Measures.

Big Data 2021 May 13. Epub 2021 May 13.

Key Laboratory of Advanced Process Control for Light Industry, Ministry of Education, Jiangnan University, Wuxi, China.

Drought is the primary and dominant natural cause of stress on vegetation, and thus, it needs our full attention. Current understanding of drought across extensive spatial measures, around the world, is considerably limited. As case studies to evaluate the feasibility of utilizing space-based solar-induced chlorophyll fluorescence (SIF) across extensive spatial measures, here, we have used data from 2007 to 2017 in Heilongjiang and Jiangsu provinces of China. The onset of the 2015 drought was accompanied by a substantial response of SIF from vegetation in both the provinces; these data were associated with changes in soil moisture, standardized precipitation evapotranspiration index, and emissivity. Our findings suggest that SIF can effectively provide the spatial and temporal progress of drought, as inferred through substantial associations with SIF normalized by absorbed photosynthetically active radiation (related to ) and by photosynthetically active radiation . For the depiction of onset to drought, SIF, , and provide a significant association and a quicker response than the leaf area index and the normalized difference vegetation index. Furthermore, we found that the correlation between gross primary productivity and SIF is highly substantial in both Heilongjiang ( = 0.85,  < 0.001) and Jiangsu ( = 0.75,  < 0.001) during the drought period. Our results indicate that continuing evaluation from space-based SIF can indeed provide an understanding of the seasonal differences in vegetation for evaluating the impact of drought across extensive spatial measures.
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http://dx.doi.org/10.1089/big.2020.0350DOI Listing
May 2021

Hepatic Arterioportal Fistula Is Associated with Decreased Future Liver Remnant Regeneration after Stage-I ALPPS for Hepatocellular Carcinoma.

J Gastrointest Surg 2021 May 7. Epub 2021 May 7.

Department of Hepatobiliary Surgery and Liver transplantation, the First Affiliated Hospital of Guangxi Medical University, Shuangrong Raod 6, Nanning, 530021, China.

Background: Hepatocellular carcinoma (HCC) patients often developed hepatic arterioportal fistula (APF). The aim of this study is to evaluate the impact of APF on future liver remnant (FLR) regeneration and surgical outcomes after the first stage of associating liver partition and portal vein ligation for staged hepatectomy (stage-I ALPPS).

Methods: Consecutive HCC patients who underwent ALPPS at our center between March 2017 and May 2019 were retrospectively studied. Data for the association between APF and clinicopathological details, liver volume, and surgical outcomes were analyzed.

Results: The enrolled 35 HCC patients were divided into three groups: 15 patients with preoperative APF were classified as the APF I group, 10 patients developed APF after stage-I ALPPS as the APF II group, whereas the other 10 patients without APF before and after stage-I ALPPS as the control group. After stage-I ALPPS, patients in the APF I and APF II groups had lower kinetic growth rate (KGR) of FLR volume (6.1±3.2%, 11.4±8.4%, 25.0±8.8% per week, respectively, P<0.001) and took longer median time to reach the sufficient FLR volume for stage-II ALPPS (17.5 days, 12 days, 6 days, respectively, P<0.001) than those in the control group. Meanwhile, the incidence of posthepatectomy liver failure (PHLF) in the APF I and APF II groups was significantly higher than that of the control group (P=0.007). There are 27 (77.1%) patients who completed stage-II ALPPS. The overall survival (OS) rates at 1 and 3 years were 59.3% and 35.1%, whereas the disease-free survival (DFS) rates at 1 and 3 years were 44.4% and 22.9%, respectively.

Conclusions: Hepatic APF is significantly associated with decreased FLR regeneration and a higher risk of PHLF after stage-I ALPPS. HCC patients who are to undergo ALPPS may benefit from the timely perioperative intervention of APF.
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http://dx.doi.org/10.1007/s11605-021-05022-0DOI Listing
May 2021

Solid phase extraction of 16 polycyclic aromatic hydrocarbons from environmental water samples by π-hole bonds.

J Chromatogr A 2021 May 15;1645:462067. Epub 2021 Mar 15.

School of Public Health, Shanxi Medical University, Taiyuan 030001, China. Electronic address:

Through theoretical computation, it was demonstrated that perfluorobenzene can form π-hole⋅⋅⋅π bonds with polycyclic aromatic hydrocarbons (PAHs). Then, the π-hole bond was firstly introduced in solid phase extraction in which perfluorobenzene-bonded silica sorbent was synthesized and used for the solid phase extraction of sixteen PAHs in water. Compared with the traditional octadecyl silica sorbent, the perfluorobenzene-bonded silica sorbent showed higher adsorbabilities for the PAHs with 4-6 benzene rings, for which the recoveries increased by approximately 20%. Under the optimized conditions, the proposed SPE-HPLC-FLD/UV method was successfully applied for the analysis of 16 PAHs in river water and waste water samples with the limits of detection ranged from 0.002 to 0.08 μg⋅L. In addition, when the perfluorobenzene-bonded silica sorbent compared with the phenyl-bonded silica sorbent, the results indicated that π-hole⋅⋅⋅π bonds between perfluorobenzene and PAHs were stronger than the π-π interactions between the PAHs and benzene in hexane solution, which highlights the remarkable potential for the application of the π-hole bond in the SPE field.
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http://dx.doi.org/10.1016/j.chroma.2021.462067DOI Listing
May 2021

Spatiotemporal Heterogeneity of Chlorophyll Content and Fluorescence Response Within Rice ( L.) Canopies Under Different Nitrogen Treatments.

Front Plant Sci 2021 25;12:645977. Epub 2021 Mar 25.

College of Biosystems Engineering and Food Science, State Key Laboratory of Modern Optical Instrumentation, Zhejiang University, Hangzhou, China.

Accurate acquisition of plant phenotypic information has raised long-standing concerns in support of crop breeding programs. Different methods have been developed for high throughput plant phenotyping, while they mainly focused on the canopy level without considering the spatiotemporal heterogeneity at different canopy layers and growth stages. This study aims to phenotype spatiotemporal heterogeneity of chlorophyll (Chl) content and fluorescence response within rice leaves and canopies. Multipoint Chl content and high time-resolved Chl fluorescence (ChlF) transient (OJIP transient) of rice plants were measured at different nitrogen levels and growth stages. Results showed that the Chl content within the upper leaves exhibited an increasing trend from the basal to the top portions but a decreasing pattern within the lower leaves at the most growth stages. Leaf Chl content within the rice canopy was higher in the lower leaves in the vegetative phase, while from the initial heading stage the pattern gradually reversed with the highest Chl content appearing in the upper leaves. Nitrogen supply mainly affects the occurrence time of the reverse vertical pattern. This could be the result of different nutritional demands of leaves transforming from sinks to sources, and it was further confirmed by the fall of the JI phase of OJIP transient in the vegetative phase and the rise in the reproductive phase. We further deduced that the vertical distribution of Chl content could have a defined pattern at a specific growth stage. Furthermore, the reduction of end acceptors at photosystem I (PSI) electron acceptor side per cross section (RE/CS) was found to be a potential sensitive predictor for identifying the vertical heterogeneity of leaf Chl content. These findings provide prior knowledge on the vertical profiles of crop physiological traits, which explore the opportunity to develop more efficient plant phenotyping tools for crop breeding.
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http://dx.doi.org/10.3389/fpls.2021.645977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028447PMC
March 2021

Bipartite Network of Interest (BNOI): Extending Co-Word Network with Interest of Researchers Using Sensor Data and Corresponding Applications as an Example.

Sensors (Basel) 2021 Mar 1;21(5). Epub 2021 Mar 1.

Key Laboratory of Advanced Process Control for Light Industry, Ministry of Education, Jiangnan University, Wuxi 214122, China.

Traditional co-word networks do not discriminate keywords of researcher interest from general keywords. Co-word networks are therefore often too general to provide knowledge if interest to domain experts. Inspired by the recent work that uses an automatic method to identify the questions of interest to researchers like "problems" and "solutions", we try to answer a similar question "what sensors can be used for what kind of applications", which is great interest in sensor- related fields. By generalizing the specific questions as "questions of interest", we built a knowledge network considering researcher interest, called bipartite network of interest (BNOI). Different from a co-word approaches using accurate keywords from a list, BNOI uses classification models to find possible entities of interest. A total of nine feature extraction methods including N-grams, Word2Vec, BERT, etc. were used to extract features to train the classification models, including naïve Bayes (NB), support vector machines (SVM) and logistic regression (LR). In addition, a multi-feature fusion strategy and a voting principle (VP) method are applied to assemble the capability of the features and the classification models. Using the abstract text data of 350 remote sensing articles, features are extracted and the models trained. The experiment results show that after removing the biased words and using the ten-fold cross-validation method, the F-measure of "sensors" and "applications" are 93.2% and 85.5%, respectively. It is thus demonstrated that researcher questions of interest can be better answered by the constructed BNOI based on classification results, comparedwith the traditional co-word network approach.
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http://dx.doi.org/10.3390/s21051668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957500PMC
March 2021

Efficacy of the association liver partition and portal vein ligation for staged hepatectomy for the treatment of solitary huge hepatocellular carcinoma: a retrospective single-center study.

World J Surg Oncol 2021 Mar 30;19(1):95. Epub 2021 Mar 30.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.

Background: The feasibility of association liver partition and portal vein ligation for staged hepatectomy (ALPPS) for solitary huge hepatocellular carcinoma (HCC, maximal diameter ≥ 10 cm) remains uncertain. This study aims to evaluate the safety and the efficacy of ALPPS for patients with solitary huge HCC.

Methods: Twenty patients with solitary huge HCC who received ALPPS during January 2017 and December 2019 were retrospectively analyzed. The oncological characteristics of contemporaneous patients who underwent one-stage resection and transcatheter arterial chemoembolization (TACE) were compared using propensity score matching (PSM).

Results: All patients underwent complete two-staged ALPPS. The median future liver remnant from the ALPPS-I stage to the ALPPS-II stage increased by 64.5% (range = 22.3-221.9%) with a median interval of 18 days (range = 10-54 days). The 90-day mortality rate after the ALPPS-II stage was 5%. The 1- and 3-year overall survival (OS) rates were 70.0% and 57.4%, respectively, whereas the 1- and 3-year progression-free survival (PFS) rates were 60.0% and 43.0%, respectively. In the one-to-one PSM analysis, the long-term survival of patients who received ALPPS was significantly better than those who received TACE (OS, P = 0.007; PFS, P = 0.011) but comparable with those who underwent one-stage resection (OS, P = 0.463; PFS, P = 0.786).

Conclusion: The surgical outcomes of ALPPS were superior to those of TACE and similar to those of one-stage resection. ALPPS is a safe and effective treatment strategy for patients with unresectable solitary huge HCC.
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http://dx.doi.org/10.1186/s12957-021-02199-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011225PMC
March 2021

Identification of Three Autophagy-Related Long Non-Coding RNAs as a Novel Head and Neck Squamous Cell Carcinoma Prognostic Signature.

Front Oncol 2020 26;10:603864. Epub 2021 Jan 26.

Department of Radiation Oncology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.

Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis. Considerable evidence indicates that autophagy and non-coding RNA play essential roles in the biological processes involved in cancers, but associations between autophagy-related long non-coding RNAs (lncRNAs) and HNSCC remain unclear. In the present study, HNSCC RNA sequences and autophagy-related gene data were extracted from The Cancer Genome Atlas database and the Human Autophagy Database. A total of 1,153 autophagy-related lncRNAs were selected calculating Pearson's correlation coefficient. Three prognosis-related autophagy lncRNAs were identified univariate Cox regression, least absolute shrinkage and selection operator analysis, and multivariate Cox regression analysis. We also constructed a prognostic model based on these autophagy-related lncRNAs and evaluated its ability to accurately and independently predict the prognosis of HNSCC patients. The area under the curve (AUC) was 0.864 (3-year) and 0.836 (5-year), and our model can independently predict the prognosis of HNSCC. The prognostic value of the three autophagy lncRNAs was confirmed analysis of samples from five databases. To further identify the functions of the three lncRNAs, a co-expression network was constructed and pathway analysis was performed. In that analysis the lncRNAs were correlated with 189 related genes and 20 autophagy-related genes, and these lncRNAs mainly involved homologous recombination, the Fanconi anemia pathway, the autophagy-related pathway, and immune-related pathways. In addition, we validated the expression levels of three lncRNAs and autophagy markers (ATG12, BECN1, and MAP1LC3B) based on TIMER, Oncomine, and HPA database analysis. Our results indicated that TTTY15 was increased in HPV positive and HPV negative HNSCC patients, and three autophagy markers were up-regulated in all HNSCCC patients. Lastly, association between three lncRNAs and autophagy markers was performed, and our results showed that TTTY15 and MIF-AS1 were associated with autophagy markers. Collectively, these results suggested that three autophagy-related lncRNAs have prognostic value in HNSCC patients.
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http://dx.doi.org/10.3389/fonc.2020.603864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871905PMC
January 2021

First Report of White Rust Disease Caused by Albugo koreana on Camelina sativa in China.

Plant Dis 2021 Jan 26. Epub 2021 Jan 26.

Tarim University, 12483, College of Life Sciences, Aral, Xinjiang, China;

Camelina sativa, an herbaceous annual plant in the family Brassicaceae, is especially well known for its oilseed crop that produce camelina oil (Hovsepyan et al. 2008). In April 2016, white blister rust disease on C. sativa were observed in a cultivated farmland with an incidence of about 60% in Xinyuan County (43°33'39.17"N, 83°14'54.04"E), Xinjiang, China. Symptoms appeared as light-yellow chlorotic spots on the upper surface of the leaves and white blister on the corresponding lower surface. Blister sori were white, oval to ellipsoidal, scattered or coalesce, and 1.8 to 4 mm in diameter. Two representative voucher specimens were deposited in the Mycological Herbarium of Tarim University (HMUT 2527 and HMUT 2528), Aral, China. Sporangiophores hyaline, clavate or cylindrical, straight to slightly curved, (23.7 to) 27.9 to 37.9 (to 42.1) (av. 31) × (7.9 to) 9.6 to 13.7 (to 15.1) (av. 11.4) μm (n = 30), thick-walled on their lower parts, bearing sporangia in chains. Primary sporangia were globose to subglobose, wall equal thickness, and (9.5 to) 10.6 to 13.2 (to 14.3) (av. 11.9) μm in diameter (n = 50). Secondary sporangia were mostly subglobose to ovoid, with a subtruncated base, and (12.1 to) 13.2 to 16.9 (to 18) (av. 15.1) μm × (11 to) 12.1 to 15 (to 16.1) (av. 13.4) μm in size (n = 50). Oogonia were globose to subglobose, (39.7 to) 42.7 to 51.7 (to 54.1) (av. 48.3) μm in diameter (n = 30), irregular. Oospores were globose to subglobose, brown, (34.5 to) 37 to 42.7 (to 45.2) (av. 41.1) μm in diameter (n = 30), 3 to 5 μm wall in thickness, with single warts, 1.5 to 4 × 2 to 3.5 μm (n = 30). The morphological characteristics of specimens were consistent with those of Albugo koreana (Choi et al. 2007). To confirm the identification, genomic DNA were extracted directly from sori on diseased leaves from isolates HMUT 2527 and HMUT 2528, respectively. The internal transcribed spacer (ITS) rDNA and cytochrome oxidase II (cox2) mtDNA were amplified with primers DC6/LR-0 described by Choi et al. (2006) and cox2-F/cox2-R described by Hudspeth et al. (2000), respectively. A BLASTn search revealed that the ITS rDNA sequences (GenBank accession Nos. MW135444 and MW135445) were 99% (838/844 nucleotides)identical to that of A. koreana from Capsella bursa-pastoris (AY929829), and the cox2 sequences (GenBank accession Nos. MW147150 and MW147151) were 100% (567/567 nucleotides) identical to that of A. koreana from C. bursa-pastoris (AY927048). Based on the concatenated ITS and cox2 sequences, Maximum Likelihood and Bayesian analysis showed that pathogen from C. sativa with the reference isolate of A. koreana (ex C. bursa-pastoris) with high bootstrap support values and maximum posterior probability (100 ML BS and 1.00 BPP, respectively). For pathogenicity, sporangia collected from the infected leaves were suspended in sterile water at 4°C for 2 hours to improve zoospore release, and the zoospore suspension obtained from sporangial suspension (1×105 sporangia/ml) was inoculated to the lower surface of six healthy potted plants. Three non-inoculated plants were served as controls. Each plant was kept in a separate plastic humid chamber in a greenhouse with 25°C and 80% humidity for 15 days. Typical symptoms of white rust pustules developed on the inoculated plants were identical to that observed on the originally infected leaves. Control plants remained symptomless.. Based on morphological characteristics, molecular data, as well as pathogenicity tests, the pathogen on C. sativa was identified as Albugo koreana. A. koreana aslo is reported only on C. bursa-pastoris in Korea (Choi et al. 2007; Farr and Rossman 2020). To our knowledge, this is the first record of white rust disease caused by A. koreana on C. sativa, and the species is new to China. This report represents a new host plant association and a new geographical expansion for this species, presenting a potential threat to camelina production in northwest China.
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http://dx.doi.org/10.1094/PDIS-11-20-2332-PDNDOI Listing
January 2021

A case of TSC2-PKD1 contiguous deletion syndrome: Clinical features and effective treatment for epilepsy.

Int J Dev Neurosci 2021 Apr 25;81(2):191-199. Epub 2021 Jan 25.

Pediatric Department, the Affiliated Hospital of Qingdao University, Shandong, P.R. China.

Polycystic kidney disease with Tuberous sclerosis is a disease caused by the deletions of the TSC2-PKD1 gene. The disease is rarely reported and the characterized manifestation is severe polycystic kidney growth. The diagnosis can be made by molecular analysis. We report the first case of PKDTS discovered in infancy in China with typical neurological and renal manifestations. The patient has infantile spasm, polycystic kidney, skin damage, hypertension, and hematuria after infection. After effective treatment of Rapamycin, the seizures were completely controlled. There was not been any renal function damage in the patient. At the same time, we review the related literature and further elaborate on the variety of clinical manifestations, treatment, and prognosis.
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http://dx.doi.org/10.1002/jdn.10088DOI Listing
April 2021

SLE non-coding genetic risk variant determines the epigenetic dysfunction of an immune cell specific enhancer that controls disease-critical microRNA expression.

Nat Commun 2021 01 8;12(1):135. Epub 2021 Jan 8.

Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, 200001, China.

Since most variants that impact polygenic disease phenotypes localize to non-coding genomic regions, understanding the consequences of regulatory element variants will advance understanding of human disease mechanisms. Here, we report that the systemic lupus erythematosus (SLE) risk variant rs2431697 as likely causal for SLE through disruption of a regulatory element, modulating miR-146a expression. Using epigenomic analysis, genome-editing and 3D chromatin structure analysis, we show that rs2431697 tags a cell-type dependent distal enhancer specific for miR-146a that physically interacts with the miR-146a promoter. NF-kB binds the disease protective allele in a sequence-specific manner, increasing expression of this immunoregulatory microRNA. Finally, CRISPR activation-based modulation of this enhancer in the PBMCs of SLE patients attenuates type I interferon pathway activation by increasing miR-146a expression. Our work provides a strategy to define non-coding RNA functional regulatory elements using disease-associated variants and provides mechanistic links between autoimmune disease risk genetic variation and disease etiology.
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http://dx.doi.org/10.1038/s41467-020-20460-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794586PMC
January 2021

The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus.

Nat Commun 2021 01 4;12(1):99. Epub 2021 Jan 4.

MRC London Institute of Medical Sciences, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK.

CD4 and CD8 mark helper and cytotoxic T cell lineages, respectively, and serve as coreceptors for MHC-restricted TCR recognition. How coreceptor expression is matched with TCR specificity is central to understanding CD4/CD8 lineage choice, but visualising coreceptor gene activity in individual selection intermediates has been technically challenging. It therefore remains unclear whether the sequence of coreceptor gene expression in selection intermediates follows a stereotypic pattern, or is responsive to signaling. Here we use single cell RNA sequencing (scRNA-seq) to classify mouse thymocyte selection intermediates by coreceptor gene expression. In the unperturbed thymus, Cd4Cd8a selection intermediates appear before Cd4Cd8a selection intermediates, but the timing of these subsets is flexible according to the strength of TCR signals. Our data show that selection intermediates discriminate MHC class prior to the loss of coreceptor expression and suggest a model where signal strength informs the timing of coreceptor gene activity and ultimately CD4/CD8 lineage choice.
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http://dx.doi.org/10.1038/s41467-020-20306-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782583PMC
January 2021

Reduced pericyte and tight junction coverage in old diabetic rats are associated with hyperglycemia-induced cerebrovascular pericyte dysfunction.

Am J Physiol Heart Circ Physiol 2021 02 11;320(2):H549-H562. Epub 2020 Dec 11.

Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.

Diabetes mellitus (DM) is one of the primary pathological factors that contributes to aging-related cognitive impairments, but the underlying mechanisms remain unclear. We recently reported that old DM rats exhibited impaired myogenic responses of the cerebral arteries and arterioles, poor cerebral blood flow autoregulation, enhanced blood-brain barrier (BBB) leakage, and cognitive impairments. These changes were associated with diminished vascular smooth muscle cell contractile capability linked to elevated reactive oxygen species (ROS) and reduced ATP production. In the present study, using a nonobese T2DN DM rat, we isolated parenchymal arterioles (PAs), cultured cerebral microvascular pericytes, and examined whether cerebrovascular pericyte in DM is damaged and whether pericyte dysfunction may play a role in the regulation of cerebral hemodynamics and BBB integrity. We found that ROS and mitochondrial superoxide production were elevated in PAs isolated from old DM rats and in high glucose (HG)-treated α-smooth muscle actin-positive pericytes. HG-treated pericytes displayed decreased contractile capability in association with diminished mitochondrial respiration and ATP production. Additionally, the expression of advanced glycation end products, transforming growth factor-β, vascular endothelial growth factor, and fibronectin were enhanced, but claudin 5 and integrin β1 was reduced in the brain of old DM rats and HG-treated pericytes. Further, endothelial tight junction and pericyte coverage on microvessels were reduced in the cortex of old DM rats. These results demonstrate our previous findings that the impaired cerebral hemodynamics and BBB leakage and cognitive impairments in the same old DM model are associated with hyperglycemia-induced cerebrovascular pericyte dysfunction. This study demonstrates that the loss of contractile capability in pericytes in diabetes is associated with enhanced ROS and reduced ATP production. Enhanced advanced glycation end products (AGEs) in diabetes accompany with reduced pericyte and endothelial tight junction coverage in the cortical capillaries of old diabetic rats. These results suggest our previous findings that the impaired cerebral hemodynamics, BBB leakage, and cognitive impairments in old DM model are associated with hyperglycemia-induced cerebrovascular pericyte dysfunction.
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http://dx.doi.org/10.1152/ajpheart.00726.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082790PMC
February 2021

Three Genes Predict Prognosis in Microenvironment of Ovarian Cancer.

Front Genet 2020 2;11:990. Epub 2020 Sep 2.

Department of Radiation Oncology, The Second Affiliated Hospital, Xi'anjiao Tong University, Xi'an, China.

Ovarian cancer (OC) is the deadliest gynecological cancer in women. Immune cell infiltration has a critical role in regulating carcinogenesis and prognosis in OC. To identify prognostic genes relevant to the tumor microenvironment in OC, we investigated the association between OC and gene expression profiles. Results obtained with the ESTIMATE R tool showed that immune score and stromal score were correlated with lymphatic invasion, and high immune score predicted a favorable prognosis. A total of 342 common differentially expressed genes were identified according to the two scores; these genes were mainly involved in immune response, extracellular region, and serine-type endopeptidase activity. Three immune-related prognostic genes were selected by univariate and multivariate Cox regression analysis. We further established a prognostic model and validated the prognostic value of three hub genes in different databases; our results showed that this model could accurately predict survival and evaluate prognosis independent of clinical characteristics. Three hub genes have prognostic value in OC. TIMER analysis revealed that the three genes were correlated with different immune cells. Low levels of macrophage infiltration and high levels of CD4+ T cell infiltration were associated with favorable survival outcomes. Arm-level gain of GYPC was correlated with neutrophils and dendritic cells. These findings indicate that CXCR4, GYPC, and MMP12 modulate prognosis via effects on the infiltration of immune cells. Thus, these genes represent potential targets for immune therapy in OC.
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http://dx.doi.org/10.3389/fgene.2020.00990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492617PMC
September 2020

A novel duplex SYBR Green real-time PCR with melting curve analysis method for beef adulteration detection.

Food Chem 2021 Feb 26;338:127932. Epub 2020 Aug 26.

China Meat Research Center, 100068 Beijing, China; Beijing Key Laboratory of Meat Processing Technology, 100068 Beijing, China. Electronic address:

An efficient and reliable duplex SYBR Green real-time quantitative PCR (qPCR) method for beef products adulteration detection was developed based on bovine specific and vertebrate universal primers. By analyzing the numbers, positions (Tm value) of melting curve peaks of the duplex PCR products, we simultaneously identified bovine and preliminary screened non-bovine in samples, and also semi-quantified the bovine percentage according to the area ratios of peaks. All of these were necessary for adulteration determination. The specific and universal primers were designed based on mitochondrial genes ND4 and 16S rRNA respectively, their amplicons Tm values were 72.6 ± 0.5 °C and 79-81 °C. There might be some other peaks at 74-78 °C and above 81 °C if non-bovine components existed. Thelimit of detectionwas 1 pgforbovineDNA, and1 - 30 pg fornon-bovineDNAbasedon differentspecies.
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http://dx.doi.org/10.1016/j.foodchem.2020.127932DOI Listing
February 2021

Association of CD14 rs2569190 G/A genetic polymorphism with the severity of enterovirus 71 infection in Chinese children.

Virology 2020 09 7;548:25-30. Epub 2020 Jun 7.

Department of Pediatrics, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, Shandong, 266000, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.virol.2020.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724738PMC
September 2020

Identifying proteins bound to native mitotic ESC chromosomes reveals chromatin repressors are important for compaction.

Nat Commun 2020 08 17;11(1):4118. Epub 2020 Aug 17.

Lymphocyte Development Group, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.

Epigenetic information is transmitted from mother to daughter cells through mitosis. Here, to identify factors that might play a role in conveying epigenetic memory through cell division, we report on the isolation of unfixed, native chromosomes from metaphase-arrested cells using flow cytometry and perform LC-MS/MS to identify chromosome-bound proteins. A quantitative proteomic comparison between metaphase-arrested cell lysates and chromosome-sorted samples reveals a cohort of proteins that were significantly enriched on mitotic ESC chromosomes. These include pluripotency-associated transcription factors, repressive chromatin-modifiers such as PRC2 and DNA methyl-transferases, and proteins governing chromosome architecture. Deletion of PRC2, Dnmt1/3a/3b or Mecp2 in ESCs leads to an increase in the size of individual mitotic chromosomes, consistent with de-condensation. Similar results were obtained by the experimental cleavage of cohesin. Thus, we identify chromosome-bound factors in pluripotent stem cells during mitosis and reveal that PRC2, DNA methylation and Mecp2 are required to maintain chromosome compaction.
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http://dx.doi.org/10.1038/s41467-020-17823-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431861PMC
August 2020

[Clinical characteristics and epidemiological analysis of pathogenic bacteria of severe abdominal infection in surgical intensive care unit].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2020 Jul;32(7):792-796

Department of Critical Care Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China. Corresponding author: Tang Zhanhong, Email:

Objective: To study the clinical characteristics of patients with severe abdominal infection and the epidemiological characteristics of pathogenic bacteria in a hospital, to provide a basis for rational use of antibiotics and reduce the drug resistance rate of pathogens.

Methods: A retrospective analysis was performed on 237 patients with abdominal disease as the primary disease admitted to the surgical intensive care unit (ICU) of the First Affiliated Hospital of Guangxi Medical University from January 1st, 2017 to December 31st, 2019. They were divided into two groups according to whether abdominal infection occurred or not. The clinical features of patients in both groups were analyzed, including gender, age, acute physiology and chronic health evaluation II (APACHE II) score, chronic underlying diseases, primary abdominal site, abdominal trauma or bleeding, multiple organ dysfunction syndrome (MODS) involving organs and surgical treatment. At the same time, the bacterial origin, bacterial distribution and antibiotics sensitivity test results of patients with abdominal infection were recorded.

Results: Abdominal infection occurred in 141 of the 237 patients and did not occur in the remaining 96 patients. There were no statistically significant differences between the abdominal infection group and the non-abdominal infection group in terms of gender, age, chronic underlying diseases, etiology and trauma. The APACHE II score in the abdominal infection group was obviously higher than that of the non-abdominal infection group (24.0±8.1 vs. 17.1±5.8, P < 0.01). Incidences of abdominal bleeding, MODS involving four or more organs, surgery and the times of surgery ≥ 3 in the abdominal infection group were significantly higher than those in the non-abdominal infection group (36.2% vs. 17.7%, 20.6% vs. 1.0%, 84.4% vs. 21.9%, 9.3% vs. 0%, all P < 0.05). Among the 141 patients with abdominal infection, 107 obtained positive microbial culture results, and a total of 133 pathogenic strains were detected, including 115 strains of bacteria (86.5%) and 18 strains of fungi (13.5%). The main source of bacteria was abdominal drainage (46.1% of non-bloody specimens and 13.9% of bloody specimens). Among the 115 bacteria, Gram-negative (G) bacteria were the most common (72.2%) and Gram-positive (G) bacteria accounted for 27.8%. Escherichia coli and Acinetobacter baumannii were the top two G bacteria (40.9% and 13.9%, respectively), and enterococcus faecalis accounted for the largest proportion of G bacteria (7.8%). The pathogenic bacteria of abdominal infection were sensitive to tigacycline.

Conclusions: The patients with abdominal infection in our hospital had high APACHE II score, more organs failure and were easily complicated with intraperitoneal hemorrhage and required surgical intervention and even repeated surgery. The pathogenic bacteria in patients with abdominal infection in ICU were mainly G bacteria, and the rate of multi-drug resistance of Acinetobacter baumannii was high. Empirical anti-infective treatment should be started as soon as possible according to the microbial spectrum of the region until the pathogenic bacteria results are obtained. Broad-spectrum antimicrobial therapy and combined antimicrobial therapy are recommended for the healthcare acquired abdominal infection in hospital.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200430-00354DOI Listing
July 2020

Evaluation of anemia, malnutrition, mineral, and bone disorder for maintenance hemodialysis patients based on bioelectrical impedance vector analysis (BIVA).

Clin Exp Nephrol 2020 Dec 10;24(12):1162-1176. Epub 2020 Aug 10.

Department of Nephrology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Rd, Wuxi, Jiangsu, 214023, China.

Background: ESRD (End-stage renal disease) treatment is a comprehensive medical process and requires numerous serological biochemical tests (SBTs) in diagnosis. To reduce these invasive, expensive, cumbersome, and time-consuming SBTs, there is a need to develop an alternative serological biochemical composition evaluation method. Bioelectrical impedance analysis (BIA) is affected by body's chemical and physical components, which might be correlated with serological biochemical composition and can be potentially used to evaluate biochemical composition in hemodialysis patient treatments. In this work, the relationship of classic and specific bioelectrical impedance vector analysis (BIVA) with major serological biochemical indexes in maintenance hemodialysis (MHD) patients was examined.

Methods: Bioelectrical and biochemical datasets were measured from 280 women and 408 men and formed 3872 effective biochemical-bioelectrical records in total. Statistical analysis was performed.

Results: The results show that BIVA vectors have strong relationship with phosphorus, hemoglobin, and PTH in both male and female groups. Strong correlation was also observed between Ca, albumin, CHOL, LDLC, and BIVA vectors in the male group. In the female group, a significant correlation was observed between classic BIVA values and NT-proBNP. SVM models are effective for classifying biochemical indexes.

Conclusions: The obtained correlations and SVM classification models imply that BIVA can be used as a preliminary tool to evaluate and classify the degree of anemia, malnutrition, fluid overload, and mineral and bone disorder (MBD) in MHD patients by reducing the number of SBTs.
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http://dx.doi.org/10.1007/s10157-020-01945-1DOI Listing
December 2020

Aging exacerbates impairments of cerebral blood flow autoregulation and cognition in diabetic rats.

Geroscience 2020 10 21;42(5):1387-1410. Epub 2020 Jul 21.

Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.

Diabetes mellitus (DM) is a leading risk factor for aging-related dementia; however, the underlying mechanisms are not well understood. The present study, utilizing a non-obese T2DN diabetic model, demonstrates that the myogenic response of the middle cerebral artery (MCA) and parenchymal arteriole (PA) and autoregulation of cerebral blood flow (CBF) in the surface and deep cortex were impaired at both young and old ages. The impaired CBF autoregulation was more severe in old than young DM rats, and in the deep than the surface cortex. The myogenic tone of the MCA was enhanced at perfusion pressure in the range of 40-100 mmHg in young DM rats but was reduced at 140-180 mmHg in old DM rats. No change of the myogenic tone of the PA was observed in young DM rats, whereas it was significantly reduced at 30-60 mmHg in old DM rats. Old DM rats had enhanced blood-brain barrier (BBB) leakage and neurodegeneration, reduced vascular density, tight junction, and pericyte coverage on cerebral capillaries in the CA3 region in the hippocampus. Additionally, DM rats displayed impaired functional hyperemia and spatial learning and short- and long-term memory at both young and old ages. Old DM rats had impaired non-spatial short-term memory. These results revealed that impaired CBF autoregulation and enhanced BBB leakage plays an essential role in the pathogenesis of age- and diabetes-related dementia. These findings will lay the foundations for the discovery of anti-diabetic therapies targeting restoring CBF autoregulation to prevent the onset and progression of dementia in elderly DM.
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http://dx.doi.org/10.1007/s11357-020-00233-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525432PMC
October 2020

Prognostic Value and Immune Infiltrates of ABCA8 and FABP4 in Stomach Adenocarcinoma.

Biomed Res Int 2020 27;2020:4145164. Epub 2020 Jun 27.

Department of Radiation Oncology, The Second Affiliated Hospital, Xi'an Jiao tong University, Xi'an, 710004 Shaanxi, China.

Background: Stomach adenocarcinoma (STAD) is a common malignancy worldwide with poor prognosis. Therefore, it is important to identify a valuable prognostic biomarker for STAD. The aim of present study was to identify novel prognostic biomarkers for STAD and evaluate the potential role of hub genes in STAD.

Methods: Gene Expression Profiling Interactive Analysis (GEPIA) and Cancer RNA-Seq Nexus were performed to identify differentially expressed genes (DEGs). Subsequently, hub genes were selected by a Venn diagram, and the expression of key genes was confirmed by UALCAN database. Furthermore, survival analysis of these hub genes was performed using Oncolnc and Human Protein Atlas (HPA) database. Gene alteration status of hub genes was assessed by cBioPortal. Finally, we investigated the association between hub genes and immune cell infiltration in STAD through the Tumor Immune Estimation Resource (TIMER) and GEPIA database.

Results: Three common hub genes were obtained, including 2 downregulated DEGs (ABCA8 and FABP4) and one upregulated DEG (SLC52A3). Furthermore, increased expression of ABCA8 and FABP4 and decreased expression of SLC52A3 were correlated with poor prognosis. Meanwhile, three hub genes showed genetic alterations in various datasets of STAD. Finally, our results showed that ABCA8 and FABP4 displayed a positive correlation with immune infiltration, especially in M2 macrophages.

Conclusions: The results of this study suggest that ABCA8 and FABP4 may be used as prognostic biomarkers and correlated with immune infiltration in STAD.
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http://dx.doi.org/10.1155/2020/4145164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338980PMC
April 2021

Chinese Cases of Metachromatic Leukodystrophy with the Novel Missense Mutations in ARSA Gene.

J Mol Neurosci 2021 Feb 2;71(2):245-251. Epub 2020 Jul 2.

Pediatric Department, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, Shandong, People's Republic of China.

Metachromatic leukodystrophy(MLD) is an autosomal recessive hereditary neurodegenerative lysosomal storage disorder caused by the mutations in arylsulfatase A gene (ARSA), which results in the deficiency of ARSA enzyme. The common clinical characteristics of MLD are abnormal gait, and then gradually appears ataxia, spastic quadriplegia, optic atrophy, cortical blindness, and dementia. We describe two patients in China who were diagnosed with MLD and find that the four ARSA gene mutations (c.1115G>A, c.302G>T, c.893 G> T, and c.302G>T) are associated with MLD, in which c.893 G>T and c.302G>T are novel mutations by gene sequence and clinical manifestations, to further understand the relationship between MLD and ARSA gene.
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http://dx.doi.org/10.1007/s12031-020-01643-3DOI Listing
February 2021

Identification of Prognostic Immune-Related Genes in Pancreatic Adenocarcinoma and Establishment of a Prognostic Nomogram: A Bioinformatic Study.

Biomed Res Int 2020 9;2020:1346045. Epub 2020 Jun 9.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.

Background: The prognosis of pancreatic adenocarcinoma (PAAD) is extremely poor and has not been improved. Thus, an effective method to assess the prognosis of patients must be established to improve their survival rate.

Method: This study investigated immune-related genes that could be used as potential therapeutic targets for PAAD. Level 3 gene expression data from the PAAD cohort and the relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database. For validation, other PAAD datasets (DSE62452) were downloaded from the Gene Expression Omnibus (GEO) database. The PAAD datasets from TCGA and GEO were used to screen immune-related genes through the Molecular Signatures Database using gene set enrichment analysis. Then, the overlapping immune-related genes of the two datasets were identified. Coexpression networks of the immune-related genes were constructed.

Results: A signature of three immune-related genes (CKLF, ERAP2, and EREG) was identified in patients with PAAD. The signature could be used to divide the patients with PAAD into high- and low-risk groups based on their median risk score. Multivariate Cox regression analysis was performed to determine the independent prognostic factors of PAAD. Time-dependent receiver operating characteristic (ROC) curve analysis was conducted to assess the prediction accuracy of the prognostic signature. Last, a nomogram was established to assess the individualized prognosis prediction model based on the clinical characteristics and risk score of the TCGA PAAD dataset. The accuracy of the prognostic signature was further evaluated through functional evaluation and principal component analysis.

Conclusions: The results indicated that the signature of three immune-related genes had excellent predictive value for PAAD. These findings might help improve personalized treatment and medical decisions.
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http://dx.doi.org/10.1155/2020/1346045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301181PMC
March 2021

Microwave-assisted extraction of polysaccharides from the marshmallow roots: Optimization, purification, structure, and bioactivity.

Carbohydr Polym 2020 Jul 21;240:116301. Epub 2020 Apr 21.

Young Researchers and Elite Club, Lahijan Branch, Islamic Azad University, Lahijan, Iran. Electronic address:

The process optimization and biological characterization of marshmallow root polysaccharides (MRPs) obtained from the microwave-assisted extraction (MAE) were studied. The highest MAE-yield (14.47%) was optimized at 457.32 W and 75 °C for 26 min. The extracted crude polysaccharides were purified using ion-exchange and gel-filtration chromatographies and eluted a single symmetrical narrow peak, showing a homogenous fraction (MRP-P1) with a molecular weight of 4.87 × 10 Da. The surface morphology of polysaccharides and functional groups of MRP-P1 were determined by employing scanning electron microscopy and Fourier-transform infrared spectroscopy, respectively. The major monosaccharide composition of MRPs were the three monomers of rhamnose, galactose, and glucose. The antioxidant, antimicrobial, and antitumor activities were increased in a concentration-dependent manner (1.0-10.0 mg/mL). MRP-P1 exhibited a strong in vitro antiproliferative activity against lung (A549), liver (HepG2), and breast (MCF-7) cancer cells. The anticancer activity of polysaccharides extracted under optimal MAE conditions was highly associated with their antioxidant and antibacterial functions.
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http://dx.doi.org/10.1016/j.carbpol.2020.116301DOI Listing
July 2020

Study amino acid contents, plant growth variables and cell ultrastructural changes induced by cadmium stress between two contrasting cadmium accumulating cultivars of Brassica rapa ssp. chinensis L. (pak choi).

Ecotoxicol Environ Saf 2020 Sep 26;200:110748. Epub 2020 May 26.

Key Laboratory of Advanced Process Control for Light Industry, Ministry of Education, Jiangnan University, Wuxi, 214122, China; University of Missouri, Columbia, MO, 65211, USA. Electronic address:

Cadmium (Cd) is an inauspicious abiotic traction that not only influences crop productivity and its growth parameters, but also has adverse effects on human health if these crops are consumed. Among crops, leafy vegetables which are the good source of mineral and vitamins accumulate more Cd than other vegetables. It is thus important to study photosynthetic variables, amino acid composition, and ultrastructural localization of Cd differences in response to Cd accumulation between two low and high Cd accumulating Brassica rapa ssp. chinensis L. (pak choi) cultivars, differing in Cd accumulation ability. Elevated Cd concentrations significantly lowered plant growth rate, biomass, leaf gas exchange and concentrations of amino acids collated to respective controls of both cultivars. Electron microscopy indicated that the impact of high Cd level on ultrastructure of leaf cells was associated to affecting cell functionalities, i.e. irregular cell wall, withdrawal of cell membrane, and chloroplast structure which has negative impact on photosynthetic activities, thus causing considerable plant growth suppression. Damage in root cells were observed in the form of enlargement of vacuole. The energy dispersive micro X-ray spectroscopy of both cultivars leaves indicated that cellular structure exhibited exudates of Cd-dense material. Ultrastructural damages and phytotoxicity were more pronounced in high accumulator cultivar as compared to the low accumulator cultivar. These findings are useful in determining the mechanisms of differential Cd-tolerance among cultivars with different Cd tolerance abilities at cellular level.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110748DOI Listing
September 2020

Efficient entry of budded virions of Autographa californica multiple nucleopolyhedrovirus into Spodoptera frugiperda cells is dependent on dynamin, Rab5, and Rab11.

Insect Biochem Mol Biol 2020 08 15;123:103409. Epub 2020 May 15.

State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Integrated Pest Management on Crops in Northwestern Loess Plateau, Ministry of Agriculture, College of Plant Protection, Northwest A&F University, Yangling, Shaanxi, 712100, China. Electronic address:

Autographa californica multiple nucleopolyhedrovirus (AcMNPV), a member of the Alphabaculovirus genus of the family Baculoviridae, is an enveloped double-stranded DNA virus. Budded virions (BVs) of AcMNPV enter host cells via clathrin-mediated endocytosis. However, the route of functional intracellular trafficking of AcMNPV BVs during entry is not well established. In the current study, we found that entering BVs were colocalized mainly with cellular Rab5 and Rab11. Expression of dominant-negative (DN) Rab5 and Rab11 or RNAi-mediated down regulation of these two cellular transcripts significantly reduced BVs entry into but not egress from Spodoptera frugiperda cells (Sf9), whereas similar treatments for Rab4 and Rab7 had no apparent effect on virus infection. Combined with data from RNAi knockdowns of dynamin, and dynasore inhibition assays, our results support a model in which AcMNPV BVs enter permissive host cells by clathrin-mediated endocytosis, followed by de-envelopment of BVs predominantly within early and maturing endosomes rather than within late endosomes. Additionally, Rab11 suppression studies suggest the Rab11-dependent recycling endosomal pathway is involved in virion entry.
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http://dx.doi.org/10.1016/j.ibmb.2020.103409DOI Listing
August 2020

Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection.

Genome Biol 2020 03 23;21(1):75. Epub 2020 Mar 23.

MOE Key Lab of Systems Biomedicine, Center for Comparative Biomedicine, State Key Lab of Oncogenes and Related Genes, Shanghai Cancer Institute, Joint International Research Laboratory of Metabolic & Developmental Sciences, Institute of Systems Biomedicine, Xin Hua Hospital, Shanghai Jiao Tong University, Shanghai, 200240, China.

Background: CTCF is a key insulator-binding protein, and mammalian genomes contain numerous CTCF sites, many of which are organized in tandem.

Results: Using CRISPR DNA-fragment editing, in conjunction with chromosome conformation capture, we find that CTCF sites, if located between enhancers and promoters in the protocadherin (Pcdh) and β-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CTCF sites or not. Moreover, computational simulation in silico and genetic deletions in vivo as well as dCas9 blocking in vitro revealed balanced promoter usage in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem CTCF sites in the Pcdh and immunoglobulin heavy chain (Igh) clusters. Furthermore, CTCF insulators promote, counter-intuitively, long-range chromatin interactions with distal directional CTCF sites, consistent with the cohesin "loop extrusion" model. Finally, gene expression levels are negatively correlated with CTCF insulators located between enhancers and promoters on a genome-wide scale. Thus, single CTCF insulators ensure proper enhancer insulation and promoter activation while tandem CTCF topological insulators determine balanced spatial contacts and promoter choice.

Conclusions: These findings have interesting implications on the role of topological chromatin insulators in 3D genome folding and developmental gene regulation.
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http://dx.doi.org/10.1186/s13059-020-01984-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087399PMC
March 2020

Sex differences in the structure and function of rat middle cerebral arteries.

Am J Physiol Heart Circ Physiol 2020 05 27;318(5):H1219-H1232. Epub 2020 Mar 27.

Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.

Epidemiological studies demonstrate that there are sex differences in the incidence, prevalence, and outcomes of cerebrovascular disease (CVD). The present study compared the structure and composition of the middle cerebral artery (MCA), neurovascular coupling, and cerebrovascular function and cognition in young Sprague-Dawley (SD) rats. Wall thickness and the inner diameter of the MCA were smaller in females than males. Female MCA exhibited less vascular smooth muscle cells (VSMCs), diminished contractile capability, and more collagen in the media, and a thicker internal elastic lamina with fewer fenestrae compared with males. Female MCA had elevated myogenic tone, lower distensibility, and higher wall stress. The stress/strain curves shifted to the left in female vessels compared with males. The MCA of females failed to constrict compared with a decrease of 15.5 ± 1.9% in males when perfusion pressure was increased from 40 to 180 mmHg. Cerebral blood flow (CBF) rose by 57.4 ± 4.4 and 30.1 ± 3.1% in females and males, respectively, when perfusion pressure increased from 100 to 180 mmHg. The removal of endothelia did not alter the myogenic response in both sexes. Functional hyperemia responses to whisker-barrel stimulation and cognition examined with an eight-arm water maze were similar in both sexes. These results demonstrate that there are intrinsic structural differences in the MCA between sexes, which are associated with diminished myogenic response and CBF autoregulation in females. The structural differences do not alter neurovascular coupling and cognition at a young age; however, they might play a role in the development of CVD after menopause. Using perfusion fixation of the middle cerebral artery (MCA) in calcium-free solution at physiological pressure and systematically randomly sampling the sections prepared from the same M2 segments of MCA, we found that there are structural differences that are associated with altered cerebral blood flow (CBF) autoregulation but not neurovascular coupling and cognition in young, healthy Sprague-Dawley (SD) rats. Understanding the intrinsic differences in cerebrovascular structure and function in males and females is essential to develop new pharmaceutical treatments for cerebrovascular disease (CVD).
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http://dx.doi.org/10.1152/ajpheart.00722.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346534PMC
May 2020