Publications by authors named "Xinyu Yang"

244 Publications

Emerging Role of LncRNAs in Ischemic Stroke-Novel Insights into the Regulation of Inflammation.

J Inflamm Res 2021 7;14:4467-4483. Epub 2021 Sep 7.

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.

As a crucial kind of pervasive gene, long noncoding RNAs (lncRNAs) are abundant and key players in brain function as well as numerous neurological disorders, especially ischemic stroke. The mechanisms underlying ischemic stroke include angiogenesis, autophagy, apoptosis, cell death, and neuroinflammation. Inflammation plays a vital role in the pathological process of ischemic stroke, and systemic inflammation affects the patient's prognosis. Although a great deal of research has illustrated that various lncRNAs are closely relevant to regulate neuroinflammation and microglial activation in ischemic stroke, the specific interactional relationships and mechanisms between lncRNAs and neuroinflammation have not been described clearly. This review aimed to summarize the therapeutic effects and action mechanisms of lncRNAs on ischemia by regulating inflammation and microglial activation. In addition, we emphasize that lncRNAs have the potential to modulate inflammation by inhibiting and activating various signaling pathways, such as microRNAs, NF-κB and ERK.
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http://dx.doi.org/10.2147/JIR.S327291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434908PMC
September 2021

Dopamine promotes the progression of AML via activating NLRP3 inflammasome and IL-1β.

Hum Immunol 2021 Sep 8. Epub 2021 Sep 8.

Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China. Electronic address:

Mental stress has been shown to activate sympathetic adrenergic system to produce dopamine and finally promote the progression of cancer. Dopamine can also regulate the immune system through secreting kinds of cytokines. However, what role does dopamine play in acute myeloid leukemia (AML) remains unclear. Here, we investigated the effects and mechanisms of dopamine in NLRP3 inflammasome activation and cellular viability of acute myeloid leukemia U937 cells. Our results showed that dopamine enhanced the viability of U937 cells and activated the NLRP3 inflammasome in U937 cells. To further explore the mechanism of dopamine on U937 cells, we examined the expression level of dopamine receptors (DRs). We found that the mRNA expression level of DR5 in U937 cells was significantly higher than other dopamine receptors. Furthermore, we treated U937 cells with DR1/2/3/5 antagonist before dopamine, and it manifestly reversed the NLRP3 inflammasome activation and the viability-enhancing effect in U937 cells induced by dopamine. Anti-IL-1β antibody also could partly reversed the viability-enhancing effect by dopamine. We concluded that dopamine could enhance the viability of U937 cells through DR1/5 receptor pathway and activate NLRP3 inflammasome.
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http://dx.doi.org/10.1016/j.humimm.2021.07.005DOI Listing
September 2021

Effects of zearalenone on liver development, antioxidant capacity and inflammatory factors of prepubertal gilts.

J Anim Physiol Anim Nutr (Berl) 2021 Sep 8. Epub 2021 Sep 8.

College of Animal Science and Technology, Hebei Agricultural University, Baoding, China.

Zearalenone (ZEA) is a kind of mycotoxin that pose great threat to the liver of human and livestock due to its toxicity to eukaryotic cells, however, its toxicity mechanism on prepubertal gilts liver development and function is not known. The study aimed to examine the effects of ZEA on liver development, antioxidant capacity and inflammatory factors of prepubertal gilts. Forty-eight prepubertal gilts (Landrace ×Yorkshire) were randomly divided into four groups: three treatment (T1, T2 and T3) groups and a control group. Prepubertal gilts in the control group were fed with basal diet, and those in T1, T2 and T3 groups were fed with basal diets supplemented with low, medium and high doses (200 μg/kg, 800 μg/kg and 1,600 μg/kg, respectively) of ZEA during the experiment period. The results showed that diets supplemented with ZEA significantly increased the activity of alanine aminotransferase of serum in the T3 group (p < 0.05). Besides, compared to the control group, the activities of total antioxidant capacity, superoxide dismutase, the content of tumour necrosis factor-alpha of liver in the T3 group and the relative expression level of manganese-superoxide dismutase mRNA of liver in the T2 group were significantly reduced (p < 0.05). We also performed correlation analysis among caecal microorganisms and antioxidant enzyme activities and inflammatory factor concentrations of liver. In conclusion, diets supplemented with ZEA has no obvious effect on liver development, but it can cause liver damage.
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http://dx.doi.org/10.1111/jpn.13628DOI Listing
September 2021

The novel LSD1 inhibitor ZY0511 suppresses diffuse large B-cell lymphoma proliferation by inducing apoptosis and autophagy.

Med Oncol 2021 Sep 7;38(10):124. Epub 2021 Sep 7.

Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.

Lysine-specific demethylase 1 (LSD1, also known as KDM1A) is an attractive agent for treatment of cancer. However, the anti-tumor effect of LSD1 inhibitors against diffuse large B-cell lymphoma (DLBCL) and the underlying mechanism are still unclear. Here, we report that KDM1A is overexpressed in human DLBCL tissues and negatively related to overall survival rate of DLBCL patients. ZY0511, a novel and potent LSD1 inhibitor developed by our group, inhibited the proliferation of human DLBCL cells. ZY0511 interacted with LSD1, induced methylation level of histone 3 lysine 4 and histone 3 lysine 9 in DLBCL cells. Mechanistically, transcriptome sequencing results indicated that ZY0511 induced the genes enrichment significantly related to cell cycle, autophagy, and apoptosis signaling pathways. Further study confirmed that ZY0511 blocked cell cycle at G0/G1 phase and expression of CDK4 and cyclin D1. ZY0511 decreased mitochondrial membrane potential and induced apoptosis, which can be reverted by a pan-caspase inhibitor, Z-VAD-FMK. Moreover, ZY0511 treatment significantly increased autophagy-associated marker proteins and autophagosomes formation in DLBCL cells. In vivo xenograft experiments confirmed that intraperitoneal administration of ZY0511 significantly suppressed SU-DHL-6 xenograft tumor growth in vivo. In conclusion, our findings identify that ZY0511 inhibits DLBCL growth both in vitro and in vivo via the induction of apoptosis and autophagy, and LSD1 inhibitor might be a promising strategy for treating DLBCL.
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http://dx.doi.org/10.1007/s12032-021-01572-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423655PMC
September 2021

Genome‑wide association study dissects the genetic control of plant height and branch number in response to low‑phosphorus stress in Brassica napus.

Ann Bot 2021 Sep 7. Epub 2021 Sep 7.

National Key Lab of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, China.

Background And Aims: Oilseed rape (Brassica napus) is one of the most important oil crops worldwide. Phosphorus (P) deficiency severely decreases the plant height (PH) and branch number (BN) of B. napus. However, the genetic bases controlling PH and BN in B. napus under P deficiency remain largely unknown. This study aims to mine candidate genes for PH and BN by genome-wide association study (GWAS) and determine low-P tolerance haplotypes.

Methods: An association panel of B. napus were grown in the field with a low P supply (P, 0 kg/ha) and a sufficient P supply (P, 40 kg/ha) across two years and PH and BN were investigated. More than five million single-nucleotide polymorphisms (SNPs) were used to conduct GWAS of PH and BN at two contrasting P supplies.

Key Results: A total of 2127 SNPs were strongly associated (P < 6.25×10 -07) with PH and BN at two P supplies. There was significant correlation between phenotypic variation and the number of favorable alleles of associated loci on chromosomes A10 (chrA10_821671) and C08 (chrC08_27999846), which will contribute to breeding improvement by aggregating these SNPs. BnaA10g09290D and BnaC08g26640D were identified to be associated with the chrA10_821671 and chrC08_27999846, respectively. Candidate gene association analysis and haplotype analysis showed that the inbred lines carrying ATT at 'BnaA10g09290Hap1' and AAT at 'BnaC08g26640Hap1' had higher PH than lines carrying other haplotype alleles at low P supply.

Conclusion: Our results demonstrate the power of GWAS in identifying genes of interest in B. napus and provided insights into the genetic basis of PH and BN at low P supply in B. napus. Candidate genes and favorable haplotypes may facilitate marker-based breeding efforts aimed at improving P use efficiency in B. napus.
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http://dx.doi.org/10.1093/aob/mcab115DOI Listing
September 2021

Dissecting esophageal squamous-cell carcinoma ecosystem by single-cell transcriptomic analysis.

Nat Commun 2021 Sep 6;12(1):5291. Epub 2021 Sep 6.

Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Esophageal squamous-cell carcinoma (ESCC), one of the most prevalent and lethal malignant disease, has a complex but unknown tumor ecosystem. Here, we investigate the composition of ESCC tumors based on 208,659 single-cell transcriptomes derived from 60 individuals. We identify 8 common expression programs from malignant epithelial cells and discover 42 cell types, including 26 immune cell and 16 nonimmune stromal cell subtypes in the tumor microenvironment (TME), and analyse the interactions between cancer cells and other cells and the interactions among different cell types in the TME. Moreover, we link the cancer cell transcriptomes to the somatic mutations and identify several markers significantly associated with patients' survival, which may be relevant to precision care of ESCC patients. These results reveal the immunosuppressive status in the ESCC TME and further our understanding of ESCC.
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http://dx.doi.org/10.1038/s41467-021-25539-xDOI Listing
September 2021

Prognostic value of derived neutrophil-to-lymphocyte ratio (dNLR) in patients with non-small cell lung cancer receiving immune checkpoint inhibitors: a meta-analysis.

BMJ Open 2021 09 2;11(9):e049123. Epub 2021 Sep 2.

Department of Hematology and Oncology, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China

Objectives: Derived neutrophil-to-lymphocytes ratio (dNLR) has recently been reported as a novel potential biomarker associated with prognosis of non-small cell lung cancer (NSCLC). However, evidence for the prognostic utility of dNLR in patients with NSCLC treated with immune checkpoint inhibitors (ICIs) remains inconsistent. The objective of this work was to evaluate the association between pretreatment dNLR and prognosis of patients with NSCLC treated with ICIs.

Design: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Data Sources: PubMed, EMBASE, Web of Science and the Cochrane Library were searched for eligible studies up to 16 October 2020. ELIGIBILITY CRITERIA: (1) Human subjects receiving ICIs therapy and who had been diagnosed with NSCLC; (2) the baseline values of dNLR were obtained; (3) the objective of the study was to investigate the relationships between dNLR and overall survival (OS) or progression-free survival (PFS) in NSCLC and (4) HR and 95% CI were displayed in the original article or could be extracted from Kaplan-Meier curves.

Data Extraction And Synthesis: Two investigators extracted data independently. Data synthesis was performed via systematic review and meta-analysis of eligible cohort studies. Meta-analysis was performed with Cochran's Q test and I statistics. Publication bias of studies was assessed by Begg's test and Egger's test. We used V.12.0 of the Stata statistical software.

Results: This analysis included eight studies (2456 cases) on the prognostic utility of dNLR in ICI therapy for NSCLC. The results indicate that higher dNLR significantly predicted poor OS (HR=1.65, 95% CI 1.46 to 1.88; p<0.001) and PFS (HR=1.38, 95% CI 1.23 to 1.55; p<0.001). Subgroup analyses of OS-related studies indicated that there were similar results in stratifications by ethnicity, sample size, type of HR and dNLR cut-off value. As for PFS-related studies, subgroup analyses showed no significant difference in Asian populations. Publication biases were not detected using Begg's test and Egger's linear regression test.

Conclusions: This meta-analysis indicated that elevated pretreatment dNLR may be a negative prognostic predictor for patients with NSCLC treated with ICIs. More large-sample and higher-quality studies are warranted to support our findings.

Prospero Registration Number: CRD42021214034.
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http://dx.doi.org/10.1136/bmjopen-2021-049123DOI Listing
September 2021

Single-cell profiling reveals distinct immune phenotypes that contribute to ischaemia-reperfusion injury after steatotic liver transplantation.

Cell Prolif 2021 Sep 1:e13116. Epub 2021 Sep 1.

Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Objectives: The discrepancy between supply and demand of organ has led to an increased utilization of steatotic liver for liver transplantation (LT). Hepatic steatosis, however, is a major risk factor for graft failure due to increased susceptibility to ischaemia-reperfusion (I/R) injury during transplantation.

Materials And Methods: To assess the plasticity and phenotype of immune cells within the microenvironment of steatotic liver graft at single-cell level, single-cell RNA-sequencing (scRNA-Seq) was carried out on 23 675 cells from transplanted rat livers. Bioinformatic analyses and multiplex immunohistochemistry were performed to assess the functional properties, transcriptional regulation, phenotypic switching and cell-cell interactions of different cell subtypes.

Results: We have identified 11 different cell types in transplanted livers and found that the highly complex ecosystem was shaped by myeloid-derived cell subsets that transit between different states and interact mutually. Notably, a pro-inflammatory phenotype of Kupffer cells (KCs) with high expression of colony-stimulating factor 3 (CSF3) that was enriched in transplanted steatotic livers was potentially participated in fatty graft injury. We have also detected a subset of dendritic cells (DCs) with highly expressing XCR1 that was correlated with CD8 T cells, mediating the severer steatotic liver damage by I/R injury.

Conclusions: The findings of our study provide new insight into the mechanisms by which steatosis exacerbates liver damage from I/R injury. Interventions based on these observations create opportunities in attenuating fatty liver graft injury and expanding the donor pool.
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http://dx.doi.org/10.1111/cpr.13116DOI Listing
September 2021

VAV2 is required for DNA repair and implicated in cancer radiotherapy resistance.

Signal Transduct Target Ther 2021 Aug 30;6(1):322. Epub 2021 Aug 30.

Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Radiotherapy remains the mainstay for treatment of various types of human cancer; however, the clinical efficacy is often limited by radioresistance, in which the underlying mechanism is largely unknown. Here, using esophageal squamous cell carcinoma (ESCC) as a model, we demonstrate that guanine nucleotide exchange factor 2 (VAV2), which is overexpressed in most human cancers, plays an important role in primary and secondary radioresistance. We have discovered for the first time that VAV2 is required for the Ku70/Ku80 complex formation and participates in non-homologous end joining repair of DNA damages caused by ionizing radiation. We show that VAV2 overexpression substantially upregulates signal transducer and activator of transcription 1 (STAT1) and the STAT1 inhibitor Fludarabine can significantly promote the sensitivity of radioresistant patient-derived ESCC xenografts in vivo in mice to radiotherapy. These results shed new light on the mechanism of cancer radioresistance, which may be important for improving clinical radiotherapy.
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http://dx.doi.org/10.1038/s41392-021-00735-9DOI Listing
August 2021

Integrated analysis of miRNA-mRNA regulatory networks of potato (Solanum tuberosum L.) in response to cadmium stress.

Ecotoxicol Environ Saf 2021 Aug 19;224:112682. Epub 2021 Aug 19.

College of Horticulture, Gansu Agricultural University, Lanzhou 730070, China; Gansu Provincial Key Laboratory of Aridland Crop Science, Lanzhou 730070, China. Electronic address:

Cadmium (Cd) stress is a ubiquitous abiotic stress affecting plant growth worldwide and negatively impacting crop yield and food safety. Potato is the most important non-grain crop globally, but there is limited research available on the response of this crop to Cd stress. This study explored the coping mechanism for Cd stress in potato through analyses of miRNA and mRNA. Tissue culture seedlings (20-day-old) of potato variety 'Atlantic' were cultured for up to 48 h in liquid medium containing 5 mmol/L CdCl, and phenotypic, physiological, and transcriptomic changes were observed at specific times. With the extension of Cd stress time, the potato leaves gradually wilted and curled, and root salicylic acid (SA), glutathione (GSH), and lignin contents and peroxidase (POD) activity increased, while indole-3-acetic acid (IAA) and zeatin (ZT) contents decreased. Using miRNA-seq, 161 existing miRNAs, 383 known miRNAs, and 7361 novel miRNAs were identified, and, 18 miRNAs were differentially expressed in response to Cd stress. Based on mRNA-seq, 7340 differentially expressed mRNAs (DEGs) were found. Through mRNA-miRNA integrated analysis, miRNA-target gene pairs consisting of 23 DEGs and 33 miRNAs were identified. Furthermore, "glutathione metabolism" "plant hormone signal transduction" and "phenylpropanoid biosynthesis" were established as crucial pathways in the Cd stress response of potato. Novel miRNAs novel-m3483-5p and novel-m2893-5p participate in these pathways through targeted regulation of cinnamic alcohol dehydrogenase (CAD; PG0005359) and alanine aminotransferase (POP; PG0024281), respectively. This study provides information that will help elucidate the complex mechanism of the Cd stress response in potato. Moreover, candidate miRNAs and mRNAs could yield new strategies for the development of Cd-tolerant potato breeding.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112682DOI Listing
August 2021

The Elevated Endogenous Reactive Oxygen Species Contribute to the Sensitivity of the Amphotericin B-Resistant Isolate of to Triazoles and Echinocandins.

Front Microbiol 2021 3;12:680749. Epub 2021 Aug 3.

Department of Dermatology and Venerology, Peking University First Hospital, National Clinical Research Center for Skin and Immune Diseases, Research Center for Medical Mycology, Peking University, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China.

has been frequently reported as the second cause of invasive aspergillosis (IA), as well as the leading cause in certain tropical countries. Amphotericin B (AMB) is a clinically important therapy option for a range of invasive fungal infections including invasive aspergillosis, and resistance to AMB was associated with poor outcomes in IA patients treated with AMB. Compared with the AMB-susceptible isolates of , the AMB-resistant isolates of showed a lower level of AMB-induced endogenous reactive oxygen species (ROS), which was an important cause of AMB resistance. In this study, we obtained one AMB-resistant isolate of , with an AMB MIC of 32 μg/mL, which was sensitive to triazoles and echinocandins. This isolate presented elevated endogenous ROS levels, which strongly suggested that no contribution of decreased AMB-induced endogenous ROS for AMB-resistance, opposite to those observed in . Further, we confirmed that the elevated endogenous ROS contributed to the sensitivity of the AMB-resistant isolate to triazoles and echinocandins. Further investigation is needed to elucidate the causes of elevated endogenous ROS and the resistance mechanism to AMB in .
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http://dx.doi.org/10.3389/fmicb.2021.680749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369828PMC
August 2021

Loop-mediated isothermal amplification (LAMP) assay for rapid detection of , the causal agent of sunflower black stem.

Plant Dis 2021 Aug 17. Epub 2021 Aug 17.

Shenyang Agricultural University, 98428, College of Plant Protection, Shenyang, Liaoning, China;

, the causal agent of sunflower black stem, severely affects sunflower yield and quality. A rapid and sensitive detection method is necessary for diagnosis of this disease. In this study, a loop-mediated isothermal amplification (LAMP) assay was developed for rapid detection of the pathogen from diseased sunflower tissues. The LAMP primers were designed targeting the rDNA region of the fungus. The reaction condition was optimized to 60°C water baths for 45 min. The detection limit of the LAMP assay was 100 fg DNA or 10 conidia/g seeds. The LAMP assay was validated by detecting from infected sunflower tissue samples including leaves, stems and seeds, and applied to seed samples randomly collected from sunflower fields. This LAMP assay will be useful to estimate disease prevalence and implement sustainable management of sunflower black stem.
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http://dx.doi.org/10.1094/PDIS-07-21-1409-REDOI Listing
August 2021

Advances in the application of nanotechnology in reducing cardiotoxicity induced by cancer chemotherapy.

Semin Cancer Biol 2021 Aug 8. Epub 2021 Aug 8.

Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China; College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China. Electronic address:

Advances in the development of anti-tumour drugs and related technologies have resulted in a significant increase in the number of cancer survivors. However, the incidence of chemotherapy-induced cardiotoxicity (CIC) has been rising continuously, threatening their long-term survival. The integration of nanotechnology and biomedicine has brought about an unprecedented technological revolution and has promoted the progress of anti-tumour therapy. In this review, we summarised the possible mechanisms of CIC, evaluated the role of nanoparticles (including liposomes, polymeric micelles, dendrimers, and hydrogels) as drug carriers in preventing cardiotoxicity and proposed five advantages of nanotechnology in reducing cardiotoxicity: Liposomes cannot easily penetrate the heart's endothelial barrier; optimized delivery strategies reduce distribution in important organs, such as the heart; targeting the tumour microenvironment and niche; stimulus-responsive polymer nano-drug carriers rapidly iterate; better economic benefits were obtained. Nanoparticles can effectively deliver chemotherapeutic drugs to tumour tissues, while reducing the toxicity to heart tissues, and break through the dilemma of existing chemotherapy to a certain extent. It is important to explore the interactions between the physicochemical properties of nanoparticles and optimize the highly specific tumour targeting strategy in the future.
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http://dx.doi.org/10.1016/j.semcancer.2021.08.003DOI Listing
August 2021

A 20-Year Antifungal Susceptibility Surveillance (From 1999 to 2019) for spp. and Proposed Epidemiological Cutoff Values for and : A Study in a Tertiary Hospital in China.

Front Microbiol 2021 22;12:680884. Epub 2021 Jul 22.

Department of Dermatology and Venereology, Peking University First Hospital, Beijing, China.

The emergence of resistant spp. is increasing worldwide. Long-term susceptibility surveillance for clinically isolated spp. strains is warranted for understanding the dynamic change in susceptibility and monitoring the emergence of resistance. Additionally, neither clinical breakpoints (CBPs) nor epidemiological cutoff values (ECVs) for spp. in China have been established. In this study, we performed a 20-year antifungal susceptibility surveillance for 706 isolates of spp. in a clinical laboratory at Peking University First Hospital from 1999 to 2019; and antifungal susceptibility to triazoles, caspofungin, and amphotericin B was determined by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. It was observed that was the most common species, followed by and . Forty isolates (5.7%), including , , , , and , were classified as non-wild type (non-WT). Importantly, multidrug resistance was observed among , , and isolates. mutations were characterized for 19 non-WT isolates, and TR/L98H/S297T/F495I was the most prevalent mutation during the 20-year surveillance period. The overall resistance trend of increased over 20 years in China. Furthermore, based on ECV establishment principles, proposed ECVs for and were established using gathered minimum inhibitory concentration (MIC)/minimum effective concentration (MEC) data. Consequently, all the proposed ECVs were identical to the CLSI ECVs, with the exception of itraconazole against , resulting in a decrease in the non-WT rate from 6.0 to 0.6%.
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http://dx.doi.org/10.3389/fmicb.2021.680884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339419PMC
July 2021

Gut microbiota-derived short-chain fatty acids and hypertension: Mechanism and treatment.

Biomed Pharmacother 2020 Oct 18;130:110503. Epub 2020 Aug 18.

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China. Electronic address:

Hypertension (HTN) is an growing emerging health issue around across the world. In recent years, increasing attention has been paid to the role of dysbacteriosis in HTN and its underlying mechanism. Short-chain fatty acids (SCFAs), which are novel metabolites of intestinal flora, exert substantial regulatory effects on HTN, providing an exciting avenue for novel therapies for this disease. They function primarily by activating transmembrane G protein-coupled receptors and inhibiting histone acetylation. In this review, we discuss the mechanisms underlying the complex interaction between SCFAs and gut microbiota composition to lower blood pressure by regulating the brain-gut and kidney-gut axes, and the role of high-salt diet, immune system, oxidative stress, and inflammatory mechanism in the development of HTN. Furthermore, we also discuss the various treatment strategies for HTN, including diet, antibiotics, probiotics, fecal microflora transplantation, and traditional Chinese medicine. In conclusion, manipulation of SCFAs opens new avenues to improve treatment of HTN.
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http://dx.doi.org/10.1016/j.biopha.2020.110503DOI Listing
October 2020

Impaired meningeal lymphatic vessels exacerbate early brain injury after experimental subarachnoid hemorrhage.

Brain Res 2021 Oct 22;1769:147584. Epub 2021 Jul 22.

Tianjin Neurological Institute, Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, China; Department of Neurosurgery, Tianjin Medical University General Hospital, China. Electronic address:

Background And Purpose: Blood that enters the subarachnoid space (SAS) and its breakdown products are neurotoxic and are the principal inducers of brain injury after subarachnoid hemorrhage (SAH). Recently, meningeal lymphatic vessels (MLVs) have been proven to play an important role in clearing erythrocytes that arise from SAH, as well as other macromolecular solutes. However, evidence demonstrating the relationship between MLVs and brain injury after SAH is still limited. Therefore, we performed this study to observe the effects of meningeal lymphatic impairment on early brain injury (EBI) after experimental SAH.

Methods: The MLVs of C57BL/6 male adult mice were ablated by injecting Visudyne into the cisterna magna and transcranially photoconverting it with laser light. The MLVs were then examined by immunofluorescence staining for lyve-1. Next, both the MLV-ablated group and the control group (normal mice) underwent filament perforation to model SAH or sham operation. We assessed the cortical perfusion of all the mice before SAH induction, 5 min after SAH and 24 h after SAH. In addition, we evaluated neurological function deficits by Garcia scores and measured brain water content at 24 h post SAH. Then, neuroinflammation and neural apoptosis in the mouse brain were also examined.

Results: Visudyne and transcranial photoconversion treatment notably ablated mouse MLVs. Five minutes after SAH induction, cortical perfusion was significantly impaired, and after 24 h, this impairment was ameliorated considerably in the control group but ameliorated only slightly or worsened in the MLV-ablated group. Additionally, the MLVablated group presented worse neurological function deficits and more severe brain edema than the control group. More notably, neuroinflammation and neural apoptosis were also observed.

Conclusion: Ablation of MLVs by Visudyne treatment exacerbated EBI after experimental SAH in mice. The worsening of EBI may have arisen from limited drainage of blood and other breakdown products, which are thought to cause brain edema, neuroinflammation, neuronal apoptosis and other pathological processes.
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http://dx.doi.org/10.1016/j.brainres.2021.147584DOI Listing
October 2021

Integration of Metabolomics and Transcriptomics Reveals Ketone Body and Lipid Metabolism Disturbance Related to ER Stress in the Liver.

J Proteome Res 2021 08 16;20(8):3875-3888. Epub 2021 Jul 16.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and Beijing Key Laboratory of Drug Target and Screening Research, Beijing 100050, China.

Once protein synthesis is excessive or misfolded protein becomes aggregated, which eventually overwhelms the capacity of the endoplasmic reticulum (ER), a state named ER stress would be reached. ER stress could affect many tissues, especially the liver, in which nonalcoholic fatty liver disease, liver steatosis, etc. have been reported relative. However, there is still a lack of systematic insight into ER stress in the liver, which can be obtained by integrating metabolomics and transcriptomics of the tissue. Here, tunicamycin was utilized to induce ER stress in C57BL/6N mice. Microarray and untargeted metabolomics were performed to identify the genes and metabolites significantly altered in liver tissues. Surprisingly, apart from the predictable unfolded protein response, liver lipid, arginine, and proline metabolisms were affirmed to be related to ER stress. Also, the ketone body metabolism changed most prominently in response to ER stress, with few studies backing. What is more, succinate receptor 1 (Sucnr1) may be a novel marker and therapeutical target of liver ER stress. In this study, the combination of the metabolome and transcriptome provided reliable information about liver pathological processes, including key relative pathways, potential markers, and targets involved in ER stress of the liver.
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http://dx.doi.org/10.1021/acs.jproteome.1c00167DOI Listing
August 2021

Acute Effects of Sleeve Gastrectomy on Glucose Variability, Glucose Metabolism, and Ghrelin Response.

Obes Surg 2021 Sep 8;31(9):4005-4014. Epub 2021 Jul 8.

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Purpose: This study aims to examine the changes of glucose metabolism, glucose variability (GV), and ghrelin secretion within 1 week following SG in Chinese patients with obesity.

Materials And Methods: Forty-nine patients with obesity (15 with type 2 diabetes) were enrolled to undergo SG. Within 1 week before and after surgery, liquid meal tests were performed in all subjects, and continuous glucose monitoring (CGM) was performed in diabetic patients. Blood samples were collected at 0, 15, 30, 45, 60, 120, and 180 min for glucose, C-peptide, insulin, and ghrelin analysis in liquid meal test. Mean amplitude of glucose excursions (MAGE), standard deviations (SD), and percent time-in-range (%TIR) determined by CGM were analyzed.

Results: Both in diabetic and non-diabetic groups, significant decrease was observed in glucose, insulin, C-peptide, and ghrelin. Homeostasis model assessment-insulin resistance and liver fat content was decreased. In diabetic group, MAGE and SD were decreased significantly, and the percent time-in-range was higher. The decrease in blood glucose was positively correlated with the decrease in ghrelin concentration in non-diabetic group.

Conclusion: Within 1 week after SG, both glucose metabolism and glucose variability were improved significantly. Suppression of ghrelin secretion postoperatively might be a driver of this early improved glycemia homeostasis.
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http://dx.doi.org/10.1007/s11695-021-05534-3DOI Listing
September 2021

NLRP3-activated bone marrow dendritic cells play antileukemic roles via IL-1β/Th1/IFN-γ in acute myeloid leukemia.

Cancer Lett 2021 Nov 5;520:109-120. Epub 2021 Jul 5.

Department of Hematology, Qilu Hospital, Shandong University, Jinan, 250012, China. Electronic address:

The bone marrow microenvironment of acute myeloid leukemia (AML) characterized by immunosuppressive features fosters leukemia immune escape. Elucidating the immunosuppressive mechanism and developing effective immunotherapeutic strategies are necessary. Here, we found that the Th1% and IFN-γ level were downregulated in bone marrow of AML and NLRP3-activated BMDCs promoted CD4 T cell differentiation into Th1 cells via IL-1β secretion. However, IFN-γ-producing Th1 cells were not induced by NLRP3-activated BMDCs in the presence of the NLRP3 inflammasome inhibitor MCC950 or anti-IL-1β antibody in vitro unless exogenous IL-1β was replenished. This inhibitory effect on Th1 differentiation was also observed in Nlrp3 mice or anti-IL-1β antibody-treated mice. Notably, elevated Th1 cell levels promoted apoptosis and inhibited proliferation in leukemia cells via IFN-γ secretion in vitro and in vivo. Thus, NLRP3-activated BMDCs promote the proliferation of IFN-γ-producing Th1 cells with antileukemic effects and may provide insight into the basis for leukemia immunotherapy in patients with AML.
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http://dx.doi.org/10.1016/j.canlet.2021.06.014DOI Listing
November 2021

Lipophagy: A New Perspective of Natural Products in Type 2 Diabetes Mellitus Treatment.

Diabetes Metab Syndr Obes 2021 30;14:2985-2999. Epub 2021 Jun 30.

Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.

Autophagy has been reported to involve in the pathogenesis of type 2 diabetes mellitus (T2DM), which protects the insulin target tissues and pancreatic β-cells. However, autophagy is inhibited when the cells are lipid overload. That, in turn, increases the accumulation of fat. Lipotoxicity caused by excessive lipid accumulation contributes to pathogenesis of T2DM. Therefore, it is undeniable to break the vicious circles between lipid excess and autophagy deficiency. Lipophagy, a selective form of autophagy, is characterized by selective breakdown of lipid droplets (LDs). The nutritional status of cells contributes to the way of autophagy (selective or non-selective), while selective autophagy helps to accurately remove excess substances. It seems that lipophagy could be an effective means to decrease abnormal lipid accumulation that leads to insulin resistance and β-cell impairment by removing ectopic LDs. Based on this process, many natural compounds have been reported to decrease lipid accumulation in tissues through autophagy-lysosomal pathway, which gradually highlights the significance of lipophagy. In this review, we focus on the mechanisms that lipophagy improves T2DM and natural products that are applied to induce lipophagy. It is also suggested that natural herbs with rich contents of natural products inducing lipophagy would be potential candidates for alleviating T2DM.
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http://dx.doi.org/10.2147/DMSO.S310166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256822PMC
June 2021

NLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia IL-1β Pathway.

Front Immunol 2021 15;12:661939. Epub 2021 Jun 15.

Department of Hematology, Qilu Hospital of Shandong University, Jinan, China.

NLRP3 inflammasome has been reported to be associated with the pathogenesis of multiple solid tumors. However, the role of NLRP3 inflammasome in acute myeloid leukemia (AML) remains unclear. We showed that NLRP3 inflammasome is over-expressed and highly activated in AML bone marrow leukemia cells, which is correlated with poor prognosis. The activation of NLRP3 inflammasome in AML cells promotes leukemia cells proliferation, inhibits apoptosis and increases resistance to chemotherapy, while inactivation of NLRP3 by caspase-1 or NF-κB inhibitor shows leukemia-suppressing effects. Bayesian networks analysis and cell co-culture tests further suggest that NLRP3 inflammasome acts through IL-1β but not IL-18 in AML. Knocking down endogenous IL-1β or anti-IL-1β antibody inhibits leukemia cells whereas IL-1β cytokine enhances leukemia proliferation. In AML murine model, up-regulation of NLRP3 increases the leukemia burden in bone marrow, spleen and liver, and shortens the survival time; furthermore, knocking out NLRP3 inhibits leukemia progression. Collectively, all these evidences demonstrate that NLRP3 inflammasome promotes AML progression in an IL-1β dependent manner, and targeting NLRP3 inflammasome may provide a novel therapeutic option for AML.
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http://dx.doi.org/10.3389/fimmu.2021.661939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239362PMC
June 2021

Effects of ammonia on growth performance, lipid metabolism and cecal microbial community of rabbits.

PLoS One 2021 30;16(6):e0252065. Epub 2021 Jun 30.

College of Animal Science and Technology, Hebei Agricultural University, Bao ding, China.

This study was designed to investigate the effect of ammonia on growth performance, lipid metabolism and intestinal flora of rabbits. A total of 150 female IRA rabbits (35-days-old) were randomly divided into three groups including 0 ppm (CG), 10 ppm (LAC) and 30 ppm ammonia (HAC) groups for a period of 28 days. The average daily weight gain (ADG) of rabbits was significantly reduced in LAC (-17.11%; p < 0.001) and HAC groups (-17.46%; p < 0.001) as compared with the CG. Serum concentration of high density lipoprotein (HDL) and glucose (Glu) were increased in LAC (+80.95%; +45.99; p < 0.05) and HAC groups (+219.05%; +45.89; p < 0.001), while apolipoprotein A1 (apoA1) was decreased in LAC (-58.49%; p < 0.001) and HAC groups (-36.92%; p < 0.001). The structural integrity of cecum was damaged, and the thickness of mucosa and serosa were significantly decreased in LAC and HAC. The acetate, butyrate and propionate level of cecal chyme were reduced in HAC group (-21.67%; -19.82%; -30.81%; p < 0.05). Microbial diversity and burden of Firmicutes were significantly decreased, while that of pathogenic bacteria, such as Bacteroidetes, Clostridium and Proteobacteria were increased in ammonia treated groups. Spearman's correlation confirmed that burden of Ruminococcaceae_NK4A214_group showed significantly negative correlation with acetic acid (r = -0.67; p < 0.001) while Barnesiellaceae_unclassified showed significantly positive correlation with propionic acid (r = 0.50; p < 0.001). In conclusion, ammonia treatment was responsible for an imbalance of intestinal flora, which affected lipid metabolism and damaged intestinal barrier of rabbits, resulting in low growth performance due to lipid metabolism dysfunction.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252065PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244895PMC
June 2021

Potential Gene Association Studies of Chemotherapy-Induced Cardiotoxicity: A Systematic Review and Meta-Analysis.

Front Cardiovasc Med 2021 4;8:651269. Epub 2021 Jun 4.

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Chemotherapy is widely used in the treatment of cancer patients, but the cardiotoxicity induced by chemotherapy is still a major concern to most clinicians. Currently, genetic methods have been used to detect patients with high risk of chemotherapy-induced cardiotoxicity (CIC), and our study evaluated the correlation between genomic variants and CIC. The systematic literature search was performed in the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), China Biology Medicine disc (CBMdisc), the Embase database, China National Knowledge Internet (CNKI) and Wanfang database from inception until June 2020. Forty-one studies were identified that examined the relationship between genetic variations and CIC. And these studies examined 88 different genes and 154 single nucleotide polymorphisms (SNPs). Our study indicated 6 variants obviously associated with the increased risk for CIC, including CYBA rs4673 (pooled odds ratio, 1.93; 95% CI, 1.13-3.30), RAC2 rs13058338 (2.05; 1.11-3.78), CYP3A5 rs776746 (2.15; 1.00-4.62) ABCC1 rs45511401 (1.46; 1.05-2.01), ABCC2 rs8187710 (2.19; 1.38-3.48), and HER2-Ile655Val rs1136201 (2.48; 1.53-4.02). Although further studies are required to validate the diagnostic and prognostic roles of these 6 variants in predicting CIC, our study emphasizes the promising benefits of pharmacogenomic screening before chemotherapy to minimize the CIC.
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http://dx.doi.org/10.3389/fcvm.2021.651269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213036PMC
June 2021

NBR2 promotes the proliferation of glioma cells via inhibiting p15 expression.

J BUON 2021 Mar-Apr;26(2):388-394

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.

Purpose: The purpose of this study was to investigate whether NBR2 can affect the proliferation of glioma cells by inhibiting the expression of p15, so as to promote the occurrence and development of glioma.

Methods: The expression of NBR2 in 44 glioma tissue specimens was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of NBR2 on cell viability, cell colony formation as well as cell migration and invasion abilities were examined by cell counting kit-8 (CCK-8) assay, plate cloning assay and Transwell assay. p15 protein was detected using Western blot. After simultaneous knockdown of NBR2 and p15, qRT-PCR, CCK-8, and plate cloning experiments were adopted to analyze p15 gene level, cell viability and proliferation ability, respectively.

Results: NBR2 was highly expressed in glioma tissues, and the level in stage III/IV glioma tissues was conspicuously higher than that in stage I/II. The overall survival rate of glioma patients with high NBR2 level was conspicuously lower than those with low NBR2 expression. Clinical data analysis revealed that NBR2 expression was correlated with the WHO stage of clinical patients. After knockdown of NBR2, it was found that NBR2 level, cell viability, cell proliferation ability as well as migration and invasion abilities were all conspicuously reduced. In addition, the protein level of p15 was significantly increased after NBR2 was inhibited. Meanwhile, knockout of p15 could reverse the inhibitory effect of NBR2 on glioma cell proliferation.

Conclusions: The highly-expressed NBR2 inhibits the expression of p15, thus promoting the proliferation of glioma cells.
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June 2021

Prediction of Anticancer Peptides with High Efficacy and Low Toxicity by Hybrid Model Based on 3D Structure of Peptides.

Int J Mol Sci 2021 May 26;22(11). Epub 2021 May 26.

State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.

Recently, anticancer peptides (ACPs) have emerged as unique and promising therapeutic agents for cancer treatment compared with antibody and small molecule drugs. In addition to experimental methods of ACPs discovery, it is also necessary to develop accurate machine learning models for ACP prediction. In this study, features were extracted from the three-dimensional (3D) structure of peptides to develop the model, compared to most of the previous computational models, which are based on sequence information. In order to develop ACPs with more potency, more selectivity and less toxicity, the model for predicting ACPs, hemolytic peptides and toxic peptides were established by peptides 3D structure separately. Multiple datasets were collected according to whether the peptide sequence was chemically modified. After feature extraction and screening, diverse algorithms were used to build the model. Twelve models with excellent performance (Acc > 90%) in the ACPs mixed datasets were used to form a hybrid model to predict the candidate ACPs, and then the optimal model of hemolytic peptides (Acc = 73.68%) and toxic peptides (Acc = 85.5%) was used for safety prediction. Novel ACPs were found by using those models, and five peptides were randomly selected to determine their anticancer activity and toxic side effects in vitro experiments.
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http://dx.doi.org/10.3390/ijms22115630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198792PMC
May 2021

Molecular Dynamics Simulation for the Effect of Fluorinated Graphene Oxide Layer Spacing on the Thermal and Mechanical Properties of Fluorinated Epoxy Resin.

Nanomaterials (Basel) 2021 May 20;11(5). Epub 2021 May 20.

State Key Laboratory of Power Transmission Equipment & System Security and New Technology, Chongqing University, Chongqing 400044, China.

Traditional epoxy resin (EP) materials have difficulty to meet the performance requirements in the increasingly complex operating environment of the electrical and electronic industry. Therefore, it is necessary to study the design and development of new epoxy composites. At present, fluorinated epoxy resin (F-EP) is widely used, but its thermal and mechanical properties cannot meet the demand. In this paper, fluorinated epoxy resin was modified by ordered filling of fluorinated graphene oxide (FGO). The effect of FGO interlayer spacing on the thermal and mechanical properties of the composite was studied by molecular dynamics (MD) simulation. It is found that FGO with ordered filling can significantly improve the thermal and mechanical properties of F-EP, and the modification effect is better than that of FGO with disordered filling. When the interlayer spacing of FGO is about 9 Å, the elastic modulus, glass transition temperature, thermal expansion coefficient, and thermal conductivity of FGO are improved with best effect. Furthermore, we calculated the micro parameters of different systems, and analyzed the influencing mechanism of ordered filling and FGO layer spacing on the properties of F-EP. It is considered that FGO can bind the F-EP molecules on both sides of the nanosheets, reducing the movement ability of the molecular segments of the materials, so as to achieve the enhancement effect. The results can provide new ideas for the development of high-performance epoxy nanocomposites.
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http://dx.doi.org/10.3390/nano11051344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160737PMC
May 2021

Sex hormone levels in females of different ages suffering from depression.

BMC Womens Health 2021 05 22;21(1):215. Epub 2021 May 22.

Department of Clinical Psychology, Kailuan Mental Health Center Affiliated to North China University of Science and Technology, Tangshan, China.

Background: There are only a few studies on sex hormones in females of different ages suffering from depression, and their conclusions are not uniform until now. This study aimed to investigate the correlation between the severity of depression in females and factors such as sex hormones and differences in sex hormone levels in females of different ages, exploring variations after treatment.

Methods: A total of 169 females with depression were selected and divided into the first-episode (91 cases) and recurrent (78 cases) groups. Then, on the basis of their age, the first-episode patients were divided into the young (48 cases, age < 45 years), perimenopausal (20 cases, 45-55 years), and elderly groups (23 cases, age > 55 years); the patients with recurrent depression were classified into the young (37 cases, age < 45 years), perimenopausal (19 cases, 45-55 years), and elderly groups (22 cases, age > 55 years). The patients were assessed in accordance with the International Classification of Diseases of mental and behavioral disorders. The serum progesterone, prolactin, estradiol, and testosterone levels in the patients were measured, and differences in sex hormone levels of the groups were analyzed.

Results: The estradiol level was negatively correlated with age and the prolactin level was positively correlated with occupation. The severity of depression in females was found to be negatively correlated with age. The serum progesterone and estradiol levels in the young group were significantly higher than those in the elderly group, regardless of the first episode or recurrence. Estradiol levels in the perimenopausal and elderly groups with first-episode depression were significantly higher than those in the same group with recurrent depression. However, there was no significant difference in the serum progesterone, prolactin, estradiol, and testosterone levels in the recurrent group before and after treatment.

Conclusions: Sex hormone levels, especially estradiol, varied among females of different ages suffering from depression. Recurrent depression also has a certain effect on sex hormone levels in females. Not only should the age and relapse be considered when studying the sex hormone levels of females with depression, but also attention should be paid to whether the patients have used antidepressants before their sexual hormonal testing.
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http://dx.doi.org/10.1186/s12905-021-01350-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141202PMC
May 2021

Spatiotemporal quantification of inoculum in relation to clubroot development under inoculated and naturally infested field conditions.

Plant Dis 2021 May 21. Epub 2021 May 21.

Shenyang Agricultural University, 98428, Plant Pathology, No. 120 Dongling Road, Shenhe, Shenyang, Liaoning, China, 110866;

Clubroot caused by is a destructive disease of cruciferous plants worldwide. A quantitative PCR (qPCR) system specific to was developed. Analysis of the qPCR sensitivity indicated that the lower limit of detection was 1 × 10 resting spores/mL, 1 × 10 spores/g soil, and 1 × 10 spores/g roots and seeds. The regression curves generated from the qPCR data of different samples had a parallel relationship. The difference between the theoretical and actual concentrations was lowest at 1 × 10 spores/g sample, compared to other concentrations. The biomass in soil and plant root tissues after inoculated with different spore concentrations was correlated. A correlation analysis confirmed that the clubroot incidence and disease index at six weeks after inoculation increased as the spore concentration increased. Under field conditions, the natural inoculum density of population decreased at early stage and then increased with mainly being detected at a soil depth of 0-50 cm. The horizontal distribution of varied in the field with occurrences of hot spots. This study established a qPCR-based method for quantitative detection of clubroot. The developed assay is useful for monitoring the spatiotemporal dynamics of in the field. It may also be applicable for clubroot forecasting as a part of proactive disease management.
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http://dx.doi.org/10.1094/PDIS-03-21-0653-REDOI Listing
May 2021

Association of / Gene Polymorphisms with Increased Susceptibility to Intracranial Aneurysm in a Chinese Han Population.

Neuropsychiatr Dis Treat 2021 12;17:1443-1449. Epub 2021 May 12.

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.

Objective: Several studies have reported that single-nucleotide polymorphisms (SNPs) of the / gene on chromosome 9p21.3 are associated with increased risk of intracranial aneurysm (IA). However, the association between IAs and SNPs of / in Chinese Han people is yet to be evaluated. This study examined the association of the SNPs rs10811661 and rs4977574 with IA in the Chinese Han population.

Methods: A total of 595 IA patients and 600 sex- and age-matched controls were enrolled in the study. Peripheral blood was collected and stored at -80°C until use. / was identified using polymerase chain reaction-ligase detection reaction. SNP genotyping was performed for rs10811661 and rs4977574 using a MassArray system. Associations between these two SNPs and IAs was tested with χ or Fisher's exact tests and multivariate logistic regression.

Results: rs10811661 and rs4977574 were significantly associated with IA. The frequency of rs10811661-T in IA was higher than in controls (OR 1.26, 95% CI 1.07-1.49; <0.01). There was no significant difference in frequency of haplotype between control subjects and IA patients.

Conclusion: rs10811661 and rs4977574 on 9p21.3 were strongly associated with genetic susceptibility to IA in the Chinese Han population, which emphasizes a need for further investigation.
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http://dx.doi.org/10.2147/NDT.S306542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126964PMC
May 2021

The attention networks in benign epilepsy with centrotemporal spikes: A long-term follow-up study.

J Clin Neurosci 2021 Jun 29;88:22-27. Epub 2021 Mar 29.

Department of Neurology, Anhui Provincial Children's Hospital, Hefei 230051, PR China. Electronic address:

Purpose: To evaluate the long-term prognosis of attention deficit in children with newly diagnosed benign childhood epilepsy with centrotemporal spikes (BECTS).

Methods: Attention network test (ANT) was performed over a period of 7 years on 42 patients who were newly diagnosed with BECTS, in the Department of Neurology of Anhui Provincial Children's Hospital.

Results: In the patients' group, the accuracy of ANT was lower (P = 0.000), the total response time was longer (P = 0.000), and the efficiency of orienting (P = 0.000) and alerting (P = 0.041) networks was lower than that of the control group. Accuracy was positively correlated with age of onset (b = 1.184) and negatively correlated with number of seizures (b = -1.321). After 7 years, there was no significant difference in the accuracy (P = 0.385); total response time (P = 0.661); and alerting (P = 0.797), orienting (P = 0.709), and executive control (P = 0.806) network efficiencies between the patients and controls. Accuracy was positively correlated with age of onset (b = 0.8583) and negatively correlated with number of seizures (b = -1.017) and duration of antiepileptic drugs therapy (b = -3.203).

Conclusions: In our study, the newly diagnosed BECTS patients had impaired attention network, mainly in the alerting and orienting domains. Age of onset, number of seizures, and time of antiepileptic treatment may affect the attention networks. With the remission of BECTS, the attention network dysfunction was reversed.
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http://dx.doi.org/10.1016/j.jocn.2021.03.022DOI Listing
June 2021
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