Publications by authors named "Xia Chen"

879 Publications

Recent advances in cell membrane coated metal-organic frameworks (MOFs) for tumor therapy.

J Mater Chem B 2021 May 12. Epub 2021 May 12.

Dongguan Key Laboratory of Drug Design and Formulation Technology, Key Laboratory of Research and Development of New Medical Materials of Guangdong Medical University, School of Pharmacy, Guangdong Medical University, Dongguan 523808, China.

In improving the tumor-targeting ability of metal-organic frameworks (MOFs) for tumor therapy and avoiding the clearance as well as capture by the immune system, there are still several challenges, which limit the development and bio-applications of MOFs. To overcome these challenges, various targeted modification strategies have been proposed. Amongst all the strategies, a promising cell membrane coating method has been explored and utilized for the syntheses of new cell membrane biomimetic MOFs (CMMs). Through such coating, various source cell membranes (e.g., red blood cell, immune cell, cancer cell, platelet, and fusion cell membranes) can be endowed with excellent properties such as long blood circulation, immune escape, and targeting ability. In the presented perspective, the synthetic method, characterization, and research progress in tumor therapy based on CMMs have been summarized. This is because, like many other technologies, the cell membrane coating technology also has several challenges to overcome. Hence, addressing and overcoming such challenges will promote and extend the bio-applications of MOFs which in the future may become a prospective carrier for cancer nano-medicine. Finally, the prospects and challenges of utilizing CMMs for tumor therapy have been discussed.
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http://dx.doi.org/10.1039/d1tb00453kDOI Listing
May 2021

Transcriptome Analysis of Eggplant Root in Response to Root-Knot Nematode Infection.

Pathogens 2021 Apr 13;10(4). Epub 2021 Apr 13.

State Key Laboratory of Agricultural Microbiology, Hubei Key Laboratory of Plant Pathology, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.

Eggplant ( L.), which belongs to the Solanaceae family, is an important vegetable crop. However, its production is severely threatened by root-knot nematodes (RKNs) in many countries. , a wild relative of eggplant, is employed worldwide as rootstock for eggplant cultivation due to its resistance to soil-borne diseases such as RKNs. In this study, to identify the RKN defense mechanisms, the transcriptomic profiles of eggplant and were compared. A total of 5360 differentially expressed genes (DEGs) were identified for the response to RKN infection. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that these DEGs are mainly involved in the processes of response to stimulus, protein phosphorylation, hormone signal transduction, and plant-pathogen interaction pathways. Many phytohormone-related genes and transcription factors (MYB, WRKY, and NAC) were differentially expressed at the four time points (ck, 7, 14, and 28 days post-infection). The abscisic acid signaling pathway might be involved in plant-nematode interactions. qRT-PCR validated the expression levels of some of the DEGs in eggplant. These findings demonstrate the nematode-induced expression profiles and provide some insights into the nematode resistance mechanism in eggplant.
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http://dx.doi.org/10.3390/pathogens10040470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069755PMC
April 2021

Comparative Evaluation of Seven Tigecycline Susceptibility Testing Methods for Carbapenem-Resistant .

Infect Drug Resist 2021 20;14:1511-1516. Epub 2021 Apr 20.

Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, People's Republic of China.

Purpose: Carbapenem-resistant Enterobacteriaceae (CRE) strains are extensively resistant to most antibiotics. Tigecycline is one of the few effective drugs that can be used to treat infections caused by CRE. The aim of this study was to evaluate the accuracy of different methods for detecting the susceptibility of CRE to tigecycline.

Methods: Seven commonly used drug susceptibility testing methods were compared and evaluated for the ability to determine CRE tigecycline susceptibility: broth microdilution (BMD), agar dilution method (ADM), disk diffusion method, Etest, MicroScan, Vitek2 COMPACT, and BD Phoenix 100.

Results: The minimum inhibitory concentration (MIC) of tigecycline to inhibit 50% and 90% of CRE growth (MIC and MIC, respectively) assessed by ADM and BD Phoenix 100 was the same as that determined by the reference method, BMD. The MIC was 2 µg/mL, and the MIC was 4 µg/mL. The highest number of susceptible strains was detected by MicroScan, followed by BMD, Etest, ADM, BD Phoenix 100, Vitek2 COMPACT, and disk diffusion method, in descending order. No significant differences were observed among the tigecycline susceptibility results (P > 0.05) obtained from MicroScan, Etest, BD Phoenix 100, and BMD. BMD confirmed that 82.0% of strains were susceptible to tigecycline. ADM, MicroScan, and BD Phoenix 100 yielded the categorical agreement of 96%, 92%, and 93%, respectively. No method was found to present any very major errors (VMEs), and only the Vitek2 COMPACT yielded major errors (MEs) greater than 3%.

Conclusion: Among the seven methods tested, the ADM, MicroScan, and BD Phoenix 100 methods were accurate for determining the tigecycline susceptibility of CRE. MicroScan was acceptable with better performance than other methods.
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http://dx.doi.org/10.2147/IDR.S289499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068477PMC
April 2021

Establishment of a New Model of Lumbar Intervertebral Disc Degeneration With Pathological Characteristics.

Global Spine J 2021 Apr 28:21925682211012323. Epub 2021 Apr 28.

Department of Orthopedic Surgery, 74678Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, People's Republic of China.

Study Design: A prospective study.

Objectives: Intervertebral disc degenerative disease is a common and frequently-occurring disease in adults and is the main cause of lower back pain. However, there is a lack of universal animal models to study disc degeneration.

Methods: Forty-two male New Zealand white rabbits aged 12 months were used in this study. We established an endplate ischemic disc degeneration model though surgical ligation of rabbit lumbar vertebral body segment arteries. Two weeks after surgery, 6 experimental animals were randomly selected for follow-up tests. First, ischemia and lumbar disc degeneration were confirmed using imaging techniques. Then, immunohistochemical staining was performed to observe the growth of the annulus fibrosus. Finally, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting were used to detect mRNA expression and protein content of IL-1α, TNFα, collagen II, MMP-3, aggrecan, and PLA2 in the nucleus pulposus of the disc.

Results: Imaging examination confirmed the successful construction of a lumbar disc degeneration model. Histological analysis and biochemical analysis showed a damaged intervertebral disc structure, and collagen II and aggrecan, the key extracellular matrix components of intervertebral discs, were reduced in synthesis and content. The synthesis and expression of IL-1α, TNFα, PLA2, and MMP-3 related to disc catabolism and inflammatory response were enhanced.

Conclusions: We successfully constructed a lumbar disc degeneration ischemia model, which provides a novel approach to study the pathological mechanisms involved in discogenic low back pain and to prevent and treat discogenic low back pain.
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http://dx.doi.org/10.1177/21925682211012323DOI Listing
April 2021

Enhancement the antibacterial properties of kefir by adding Lactobacillus fermentum grx08.

J Food Prot 2021 Apr 26. Epub 2021 Apr 26.

CHINA yangzhou.

Kefir is an acidic-alcoholic fermented milk that can provide probiotic benefits such as intestinal microecological balance regulation, antibacterial activity, and anti-inflammatory activity. In this study, Lactobacillus fermentum grx08 isolated from longevous people was used to further improve the health properties of kefir. L. fermentum grx08 and kefir grains obtained from Xinjiang, China were mixed at ratios of 1:1, 5:1 and 25:1 as starters. The 6 Gram-positive and Gram-negative foodborne pathogens were able to grow in the supernatant of kefir, but not in the supernatant of kefir with L. fermentum grx08. With the increasing of amount of inoculated L. fermentum grx08, the antibacterial activity of the mixed fermented kefir gradually increased. The contents of lactic acid, fumaric acid and malic acid in the mixed fermented milk were significantly increased by adding L. fermentum grx08 (P < 0.05), while the content of acetic acid decreased with the increase of L. fermentum grx08, and the content of citric acid was unaffected. This study suggest that the addition of  L. fermentum grx08 shortened the fermentation time, improved the acidity and retained the quality of fermented milk. Moreover, the antibacterial properties of kefir is enhanced by increasing the production of certain acid.
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http://dx.doi.org/10.4315/JFP-21-113DOI Listing
April 2021

Practical access to fluorescent 2,3-naphthalimide derivatives didehydro-Diels-Alder reaction.

Chem Commun (Camb) 2021 Apr 26. Epub 2021 Apr 26.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

A practical and efficient approach for the synthesis of fluorescent 2,3-naphthalimide derivatives has been developed from readily available starting materials via an intramolecular didehydro-Diels-Alder reaction, which proceeded well under room temperature, exhibiting a wide substrate scope and good functional group tolerance. The practicability of this methodology has been verified by one-step synthesis of the environmentally sensitive fluorophore 6-DMN on a gram scale with a shorter time, fewer steps and less waste disposal, and without the utilization of toxic transition metals. The present experimental and computational studies support the crucial role of the propiolimide moiety in the transformation.
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http://dx.doi.org/10.1039/d1cc01437dDOI Listing
April 2021

Character changes and Transcriptomic analysis of a cassava sexual Tetraploid.

BMC Plant Biol 2021 Apr 19;21(1):188. Epub 2021 Apr 19.

Key Laboratory of Biology and Genetic Resources of Tropical Crops, Ministry of Agriculture, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou, 571101, China.

Background: Cassava (Manihot esculenta Crantz) is an important food crop known for its high starch content. Polyploid breeding is effective in its genetic improvement, and use of 2n gametes in sexual polyploid breeding is one of the potential methods for cassava breeding and improvement. In our study, the cassava sexual tetraploid (ST), which carries numerous valuable traits, was successfully generated by hybridizing 2n female gametes SC5 (♀) and 2n male gametes SC10 (♂). However, the molecular mechanisms remain unclear. To understand these underlying molecular mechanisms behind the phenotypic alterations and heterosis in ST plants, we investigated the differences in gene expression between polyploids and diploids by determining the transcriptomes of the ST plant and its parents during the tuber root enlargement period. We also compared the characters and transcriptomes of the ST plant with its parents.

Results: The ST plant was superior in plant height, stem diameter, leaf area, petiole length, plant weight, and root weight than the parent plants, except the leaf number, which was lower. The number of starch granules was higher in the roots of ST plants than those in the parent plants after five months (tuber root enlargement period), which could be due to a higher leaf net photosynthetic rate leading to early filling of starch granules. Based on transcriptome analysis, we identified 2934 and 3171 differentially expressed genes (DEGs) in the ST plant as compared to its female and male parents, respectively. Pathway enrichment analyses revealed that flavonoid biosynthesis and glycolysis/gluconeogenesis were significantly enriched in the ST plants, which might contribute to the colors of petiole (purple-red), root epidermis (dark brown), and tuber starch accumulation, respectively.

Conclusions: After sexual polyploidization, the phenotype of ST has changed significantly in comparison to their diploid parents, mainly manifest as enlarged biomass, yield, early starch filling, deep colored petiole and root epidermis. The tetraploid plants were also mature early due to early starch grain filling. Owing to enriched flavonoid biosynthesis and glycolysis/gluconeogenesis, they are possibly resistant to adversity stresses and provide better yield, respectively.
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http://dx.doi.org/10.1186/s12870-021-02963-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056498PMC
April 2021

Bibliometric Analysis of the Scientific Literature on Adolescent Idiopathic Scoliosis.

World Neurosurg 2021 Apr 16. Epub 2021 Apr 16.

Daniel and Jane Och Spine Hospital, New York-Presbyterian Healthcare System, Columbia University Medical Center, New York, New York, USA.

Background: In recent years, there has been increasing research on adolescent idiopathic scoliosis (AIS), leading to many publications on this topic. To our knowledge, no study has focused on the research trends in this field.

Methods: Using the Web of Science Core Collection database for all articles on AIS, the number of citations, authorship, year of publication, journal of publication, country and institution of origin, and keywords were subjected to co-occurrence analysis using VOSviewer software. The top 100 most-cited articles on AIS were analyzed.

Results: Between 1985 and 2020, 2266 articles related to AIS were identified. The frequency of publication on AIS has increased substantially over time. Among all countries, the United States has contributed the most articles on AIS (n = 671). The most productive institution has been Nanjing University (n = 154). Spine topped the list of journals and has published 569 AIS-related articles, which received 19,862 total citations. The clinical description of AIS has been the most common research focus in the AIS literature.

Conclusions: The scientific literature on AIS has rapidly expanded in recent years. This study represents the updated bibliometric analysis of scientific articles on AIS and provides a research trend for the first time, which aims to give a unique insight into the development of AIS research focus and serve as a useful guide to clinicians and researchers in the field.
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http://dx.doi.org/10.1016/j.wneu.2021.04.020DOI Listing
April 2021

Serum Heparin-Binding Protein as a Potential Biomarker to Distinguish Adult-Onset Still's Disease From Sepsis.

Front Immunol 2021 31;12:654811. Epub 2021 Mar 31.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.

Adult-onset Still's disease (AOSD) is a systemic, multifactorial, autoinflammatory disease for which the etiopathogenesis is not well understood. Given the similarities in clinical and laboratory features between this disease and sepsis, and the differences in treatment strategies for these two diseases, specific diagnostic markers are crucial for the correct diagnosis and management of AOSD. Previous studies have shown plasma heparin-binding protein (HBP) is a promising potential biomarker for AOSD; thus, this study aimed to detect serum HBP levels in patients with AOSD or sepsis to assess its potential as a biomarker for differential diagnosis. We found that serum HBP levels were significantly higher in patients with active AOSD than that in those with inactive AOSD. Patients with sepsis had higher serum HBP levels compared with those who had active or inactive AOSD. We calculated the area under the receiver operating characteristic (ROC) curve to assess whether HBP could be used to differentiate active from inactive AOSD; this was 0.811 with sensitivity 0.650, specificity 0.811, and cutoff HBP value of 35.59 ng/ml. The area under the ROC curve for HBP as a biomarker to differentiate AOSD from sepsis was 0.653, with sensitivity 0.759, and specificity 0.552, and cutoff HBP value of 65.1 ng/ml. Taken together, the results of our study suggest that serum HBP could be a useful diagnostic biomarker to evaluate disease activity in patients with AOSD, and to differentiate AOSD from sepsis.
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http://dx.doi.org/10.3389/fimmu.2021.654811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044511PMC
March 2021

Piperazine-2,5-dione derivatives and an α-pyrone polyketide from Penicillium griseofulvum and their immunosuppression activity.

Phytochemistry 2021 Jun 12;186:112708. Epub 2021 Apr 12.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China. Electronic address:

Four undescribed piperazine-2,5-dione derivatives designated janthinolides C-F, and an α-pyrone-containing polyketide namely trichopyrone C, were isolated from the extract of the fungus Penicillium griseofulvum along with four known products. Among them, janthinolide C represents the first naturally occured piperazine-2,5-dione analogue featuring a cleavaged piperazinedione ring with an oxime group, while the structure of janthinolide D possesses a rare N-methoxy group in natural products. Their structures and absolute stereochemistry were elucidated based on spectroscopic data, theoretical NMR and ECD calculations, Snatzke's method, and modified Mosher's method. All compounds were evaluated for in vitro immunosuppression activity in murine splenocytes stimulated by anti-CD3/anti-CD28 mAbs, of which janthinolides B and C showed potential inhibitory activity with IC values at 9.3 and 1.3 μM, respectively.
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http://dx.doi.org/10.1016/j.phytochem.2021.112708DOI Listing
June 2021

An Insight of the First Community Infected COVID-19 Patient in Beijing by Imported Case: Role of Deep Learning-Assisted CT Diagnosis.

Chin Med Sci J 2021 Mar;36(1):66-71

Department of Infection, Beijing Haidian Section of Peking University Third Hospital (Beijing Haidian Hospital), Beijing 100080, China.

In the era of coronavirus disease 2019 (COVID-19) pandemic, imported COVID-19 cases pose great challenges to many countries. Chest CT examination is considered to be complementary to nucleic acid test for COVID-19 detection and diagnosis. We report the first community infected COVID-19 patient by an imported case in Beijing, which manifested as nodular lesions on chest CT imaging at the early stage. Deep Learning (DL)-based diagnostic systems quantitatively monitored the progress of pulmonary lesions in 6 days and timely made alert for suspected pneumonia, so that prompt medical isolation was taken. The patient was confirmed as COVID-19 case after nucleic acid test, for which the community transmission was prevented timely. The roles of DL-assisted diagnosis in helping radiologists screening suspected COVID cases were discussed.
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http://dx.doi.org/10.24920/003788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041135PMC
March 2021

Gut microbiota accelerates cisplatin-induced acute liver injury associated with robust inflammation and oxidative stress in mice.

J Transl Med 2021 04 13;19(1):147. Epub 2021 Apr 13.

Department of Obstetrics and Gynecology, First People's Hospital of Foshan, Foshan, China.

Background: Gut microbiota has been reported to be disrupted by cisplatin, as well as to modulate chemotherapy toxicity. However, the precise role of intestinal microbiota in the pathogenesis of cisplatin hepatotoxicity remains unknown.

Methods: We compared the composition and function of gut microbiota between mice treated with and without cisplatin using 16S rRNA gene sequencing and via metabolomic analysis. For understanding the causative relationship between gut dysbiosis and cisplatin hepatotoxicity, antibiotics were administered to deplete gut microbiota and faecal microbiota transplantation (FMT) was performed before cisplatin treatment.

Results: 16S rRNA gene sequencing and metabolomic analysis showed that cisplatin administration caused gut microbiota dysbiosis in mice. Gut microbiota ablation by antibiotic exposure protected against the hepatotoxicity induced by cisplatin. Interestingly, mice treated with antibiotics dampened the mitogen-activated protein kinase pathway activation and promoted nuclear factor erythroid 2-related factor 2 nuclear translocation, resulting in decreased levels of both inflammation and oxidative stress in the liver. FMT also confirmed the role of microbiota in individual susceptibility to cisplatin-induced hepatotoxicity.

Conclusions: This study elucidated the mechanism by which gut microbiota mediates cisplatin hepatotoxicity through enhanced inflammatory response and oxidative stress. This knowledge may help develop novel therapeutic approaches that involve targeting the composition and metabolites of microbiota.
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http://dx.doi.org/10.1186/s12967-021-02814-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045234PMC
April 2021

Regulation of Anion Channel LRRC8 Volume-Regulated Anion Channels in Transport of 2'3'-Cyclic GMP-AMP and Cisplatin under Steady State and Inflammation.

J Immunol 2021 May 7;206(9):2061-2074. Epub 2021 Apr 7.

The Center for Microbes, Development and Health, Chinese Academy of Sciences Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China;

The recently identified anion channel LRRC8 volume-regulated anion channels (VRACs) are heteromeric hexamers constituted with the obligate LRRC8A subunit paired with at least one of the accessory LRRC8B to LRRC8E subunits. In addition to transport chloride, taurine, and glutamate, LRRC8 VRACs also transport the anticancer agent cisplatin and STING agonists 2'3'-cyclic GMP-AMP (cGAMP) and cyclic dinucleotides; hence, they are implicated in a variety of physiological and pathological processes, such as cell swelling, stroke, cancer, and viral infection. Although the subunit composition largely determines VRAC substrate specificity, the opening of various VRAC pores under physiological and pathological settings remains enigmatic. In this study, we demonstrated that VRACs comprising LRRC8A and LRRC8E (LRRC8A/E-containing VRACs), specialized in cGAMP transport, can be opened by a protein component present in serum under resting condition. Serum depletion ablated the tonic activity of LRRC8A/E-containing VRACs, decreasing cGAMP transport in various human and murine cells. Also, heating or proteinase K treatment abolished the ability of serum to activate VRAC. Genetic analyses revealed a crucial role for cGAMP synthase (cGAS) in serum/TNF-promoted VRAC activation. Notably, the presence of cGAS on the plasma membrane, rather than its DNA-binding or enzymatic activity, enabled VRAC activation. Moreover, phospholipid PIP2 seemed to be instrumental in the membrane localization of cGAS and its association with VRACs. Corroborating a role for LRRC8A/D-containing VRACs in cisplatin transport, serum and TNF markedly potentiated cisplatin uptake and killing of cancer cells derived from human or mouse. Together, these observations provide new insights into the complex regulation of VRAC activation and suggest a novel approach to enhance the efficacy of cGAMP and cisplatin in treating infection and cancer.
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http://dx.doi.org/10.4049/jimmunol.2000989DOI Listing
May 2021

Somatic CG6015 mediates cyst stem cell maintenance and germline stem cell differentiation via EGFR signaling in Drosophila testes.

Cell Death Discov 2021 Apr 6;7(1):68. Epub 2021 Apr 6.

Department of Gynecology, the Affiliated Hospital of Jiangsu University, Jiangsu University, 212001, Zhenjiang, Jiangsu, P.R. China.

Stem cell niche is regulated by intrinsic and extrinsic factors. In the Drosophila testis, cyst stem cells (CySCs) support the differentiation of germline stem cells (GSCs). However, the underlying mechanisms remain unclear. In this study, we found that somatic CG6015 is required for CySC maintenance and GSC differentiation in a Drosophila model. Knockdown of CG6015 in CySCs caused aberrant activation of dpERK in undifferentiated germ cells in the Drosophila testis, and disruption of key downstream targets of EGFR signaling (Dsor1 and rl) in CySCs results in a phenotype resembling that of CG6015 knockdown. CG6015, Dsor1, and rl are essential for the survival of Drosophila cell line Schneider 2 (S2) cells. Our data showed that somatic CG6015 regulates CySC maintenance and GSC differentiation via EGFR signaling, and inhibits aberrant activation of germline dpERK signals. These findings indicate regulatory mechanisms of stem cell niche homeostasis in the Drosophila testis.
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http://dx.doi.org/10.1038/s41420-021-00452-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024382PMC
April 2021

A Household-Based Cross-Sectional Survey of Knowledge, Awareness and Practice Regarding Malaria in Western Area Rural District, Sierra Leone.

Front Public Health 2021 18;9:664971. Epub 2021 Mar 18.

National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

Sierra Leone is a highly endemic area for malaria, and the implementation of the National Malaria Strategic Plan (2016-2020) has reached its midpoint in 2018. To provide more specific guidance for interventions in the future, a household-based cross-sectional survey was conducted to elucidate the knowledge, awareness and practices regarding malaria and malarial control measures among the general public. Three communities (Grafton, Jui, and Kossoh) in the Western Area Rural District that were in close proximity to Sierra Leone's capital city of Freetown were included. Households were randomly selected and interviewed with a structured questionnaire covering malaria infection, diagnosis, treatment and prevention, as well as knowledge of malaria prevention. As a result, a total of 262 qualified questionnaires were included. The average cost for meals per day is ~30,000 Leones in each household. The rate of awareness, indicated by reporting having heard of malaria, was 98.1% (257/262), and 86.6% (227/262) of the respondents knew that mosquito bites are the main route of transmission. In addition, 80.9% (212/262) of the respondents sought health advice or treatment for the illness, and a similar percentage of respondents had been tested for malaria, mostly with rapid diagnostic tests (RDTs). A high demand for long-lasting insecticidal nets (72.1%) matched the serious shortage (61.8%, 162/262), and of the households that reported a lack of nets, 66 had children younger than 5 years old. In conclusion, public awareness of malaria prevention is high, based on this survey, although there was a limited use of preventive measures in these three communities and the malaria burden was still high. Therefore, the public's knowledge of malaria should be sustained and reinforced, and the distribution and use of malaria prevention measures should be promoted to supprt the achievement of the planned objectives.
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http://dx.doi.org/10.3389/fpubh.2021.664971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012796PMC
March 2021

Synthesis of Succinimides via Intramolecular Alder-Ene Reaction of 1,6-Enynes.

Org Lett 2021 Apr 2;23(8):3173-3178. Epub 2021 Apr 2.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

A novel and convenient method has been developed for the facile synthesis of functionalized succinimide derivatives via intramolecular Alder-ene reaction of 1,6-enynes. This reaction features mild and metal-free reaction conditions, which offers a green and efficient entry to synthetically important succinimide scaffolds. Preliminary mechanistic studies suggest that a diradical intermediate might be involved in this transformation.
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http://dx.doi.org/10.1021/acs.orglett.1c00888DOI Listing
April 2021

Weighted gene co-expression network analysis (WGCNA) to explore genes responsive to biofilm and immune infiltration analysis in human gingival fibroblasts cells.

Bioengineered 2021 Dec;12(1):1054-1065

Department of Prosthodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, China.

The correlation between oral bacteria and dental implants failure has been reported. However, the effect and mechanism of bacteria during dental implants is unclear. In this study, we explored key genes and candidate gene clusters in human gingival fibroblasts (HGF) cells in response to biofilm through weighted gene co-expression network analysis (WGCNA) and differential genes analysis using gene expression matrix, GSE134481, downloaded from the Gene Expression Omnibus (GEO) database. We obtained 325 genes in the module significantly associated with infection and 113 differentially expressed genes (DEGs) in the biofilm; 62 DEGs indicated significant correlation with injury. Multiple immune pathways, such as the tumor necrosis factor (TNF) signaling pathway, were considerably enriched. We obtained a candidate genes cluster containing 12 genes - , and ; we observed 5 candidate hub genes associated with infection - , and . The fraction of macrophage M0 cells was significantly increased in biofilm treatment compared with control; expression of and was significantly positively correlated with macrophage M0 cells. Our findings present a fierce inflammation changes in the transcript level of HGF in response to .
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http://dx.doi.org/10.1080/21655979.2021.1902697DOI Listing
December 2021

The common YAP activation mediates corneal epithelial regeneration and repair with different-sized wounds.

NPJ Regen Med 2021 Mar 26;6(1):16. Epub 2021 Mar 26.

Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Regeneration/repair after injury can be endowed by adult stem cells (ASCs) or lineage restricted and even terminally differentiated cells. In corneal epithelium, regeneration after a large wound depends on ASCs (limbal epithelial stem cells, LESCs), whereas repair after a small wound is LESCs-independent. Here, using rat corneal epithelial wounds with different sizes, we show that YAP activation promotes the activation and expansion of LESCs after a large wound, as well as the reprogramming of local epithelial cells (repairing epithelial cells) after a small wound, which contributes to LESCs-dependent and -independent wound healing, respectively. Mechanically, we highlight that the reciprocal regulation of YAP activity and the assembly of cell junction and cortical F-actin cytoskeleton accelerates corneal epithelial healing with different-sized wounds. Together, the common YAP activation and the underlying regulatory mechanism are harnessed by LESCs and lineage-restricted epithelial cells to cope with corneal epithelial wounds with different sizes.
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http://dx.doi.org/10.1038/s41536-021-00126-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997881PMC
March 2021

MicroRNA‑378d inhibits by targeting in vitamin D deficient ovarian granulosa cells.

Mol Med Rep 2021 May 24;23(5). Epub 2021 Mar 24.

Department of Reproductive Center, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

Vitamin D (VD) is not only associated with bone growth and development, but is also closely associated with numerous other pathological conditions. The present study aimed to investigate the effect of microRNA (miRNA/miR)‑378d on ovarian granulosa cells by regulating the round spermatid basic protein 1 () in the absence of VD. The abnormal expression of miRNAs in ovarian tissues of the VD‑deficient mouse was analyzed using transcriptome sequencing. miR‑378d, glucose transporter 4 () and aromatase () expression levels were examined via reverse transcription‑quantitative (RT‑q)PCR and western blotting. The expression levels of , and were detected in transfected mouse ovarian granulosa cells. The targeting regulation between miR‑378d and was verified using double reporter gene assay and functional rescue experiments. Among the 672 miRNAs that were differentially expressed, cluster analysis revealed that 17 were significantly upregulated and 16 were significantly downregulated. Moreover, miR‑378d showed significant upregulation, which was further verified via RT‑qPCR. It was identified that the protein expression level of was significantly downregulated. Furthermore, mRNA expression was significantly decreased in the mimic group but markedly increased in the inhibitor group. By contrast, the mRNA expression levels of and did not demonstrate any significant difference. The western blotting results indicated that the protein expression levels of and were decreased and increased, respectively, while did not show any significant change. In addition, the double reporter gene experiments confirmed that was the target gene of miR‑378d. Collectively, the present results demonstrated that miR‑378d was abnormally overexpressed in the ovarian tissues of the VD‑deficient mice, and that miR‑378d could inhibit production by targeting , which may lead to insulin resistance.
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http://dx.doi.org/10.3892/mmr.2021.12008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985995PMC
May 2021

A Rare Case of Acute Liver Failure Secondary to Diffuse Hepatic Infiltration of Small Cell Neuroendocrine Carcinoma.

Front Oncol 2021 4;11:616337. Epub 2021 Mar 4.

Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou, China.

Background: Malignant liver infiltration is an uncommon cause of acute liver failure (ALF) and has rarely been reported.

Case Presentation: We present a patient with progressive jaundice and dissociation of bilirubin and aminotransferases, who had no history of relevant liver diseases or tumor except the use of Chinese traditional drugs for a cold. An abdominal computed tomography (CT) scan showed ascites without hepatic focal lesions. Laboratory studies revealed no evidence of hepatitis or underlying autoimmune disorders. Following 8 days of conservative management ALF rapidly worsened. Contrast-enhanced CT revealed diffuse regenerative nodules in the liver. The patient underwent liver biopsy, which demonstrated that the liver was infiltrated by pulmonary neuroendocrine tumor classified as small cell lung cancer. The patient died 13 days after diagnosis.

Discussion And Conclusions: This case represents a rare cause of ALF induced by pulmonary neuroendocrine tumor of small cell type and illustrates the importance of prompt biopsy in an unknown cause of ALF.
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http://dx.doi.org/10.3389/fonc.2021.616337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969992PMC
March 2021

Thyroid Parenchyma Microcalcifications on Ultrasound for Predicting Lymph Node Metastasis in Papillary Thyroid Carcinoma: A Prospective Multicenter Study in China.

Front Oncol 2021 3;11:609075. Epub 2021 Mar 3.

Department of Ultrasound, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Cervical lymph node metastasis (LNM) was found to be clinically significant prognostic factors of patients with papillary thyroid carcinomas (PTC). Ultrasound (US) characteristics of thyroid nodules and thyroid parenchyma may be used to predict LNM. To investigate the value of nodular US features as well as thyroid parenchymal microcalcifications on US in predicting LNM in patients with PTC. This prospective study was approved by the Institutional Review Board. From January 2018 to June 2019, 971 consecutive patients with solitary PTC who underwent preoperative neck US evaluation were included from six hospitals in China. The US features of thyroid nodules as well as thyroid parenchyma microcalcifications were carefully evaluated based on the static images and dynamic clips. Univariate and multivariate analyses were performed to determine independent predictors of LNM. Of the 971 patients, 760 were female, 211 were male. According to the pathological examination, 241(24.82%) patients were found with cervical LNM (LNM positive group), while 730 (75.18%) patients were not (LNM negative group). Multiple logistic regression analysis showed that young age (<55 years old) (OR = 1.522, = 0.047), large size (>10 mm) (OR = 1.814, < 0.001), intratumoral microcalcifications (OR = 1.782, = 0.002) and thyroid parenchyma microcalcifications (OR = 1.635, = 0.046) were independent risk factors for LNM of PTC. Young age, large nodule size, intratumoral microcalcifications, as well as thyroid parenchyma microcalcifications on US are independent predictors of cervical LNM for patients with PTC.
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http://dx.doi.org/10.3389/fonc.2021.609075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968415PMC
March 2021

New immunosuppressive secondary metabolites from the endophytic fungus Aspergillus sp.

Fitoterapia 2021 Mar 19;151:104882. Epub 2021 Mar 19.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, People's Republic of China. Electronic address:

Six new metabolites, including two diphenolic derivatives (1 and 2), one pseurotin (3), one butenolide derivative (4), one benzopyran (5) and one isochromane lactone (6), together with ten known compounds (7-16) were isolated from an endophytic fungus Aspergillus sp. Their planar structures and absolute configurations were established based on techniques of MS, NMR, IR, UV, [Rh2(OCOCF3)4] complex-induced ECD, quantum chemical electronic circular dichroism (ECD) calculations, and single crystal X-ray diffraction. Structurally, compound 2 represents the first example of diphenolic derivative possessing an unusual 1-oxaspiro[2.4]heptane core bearing a 5/3 bicyclic skeleton; compound 3 represents the first example of pseurotin type natural products that only one hydroxy group is substituted at side chain. In bioassay, compounds 3, 7 and 8 exhibited potential inhibitory effect on the proliferation of anti-CD3/anti-CD28 monoclonal antibodies (mAbs) induced murine T cells, with IC50 values of (7.81 ± 0.71), (8.25 ± 0.78) and (8.84 ± 0.81) μM, respectively.
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http://dx.doi.org/10.1016/j.fitote.2021.104882DOI Listing
March 2021

Hollow Mesoporous Silica Nanoparticles Gated by Chitosan-Copper Sulfide Composites as Theranostic Agents for the Treatment of Breast Cancer.

Acta Biomater 2021 May 14;126:408-420. Epub 2021 Mar 14.

College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, P.R. China. Electronic address:

The combination of chemotherapy and photothermal therapy (PTT) into a single formulation has attracted increasing attention as a strategy for enhancing cancer treatment. Here, hollow mesoporous silica nanoparticles (HMSNs) were used as a base carrier material, loaded with the anti-cancer drug doxorubicin (DOX), and surface functionalized with chitosan (CS) and copper sulfide (CuS) nanodots to give HMSNs-CS-DOX@CuS. In this formulation, the CuS dots act as gatekeepers to seal the surface pores of the HMSNs, preventing a burst release of DOX into the systemic circulation. S-S bonds connect the CuS dots to the HMSNs; these are selectively cleaved under the reducing microenvironment of the tumor, permitting targeted drug release. This, coupled with the PTT properties of CuS, results in a potent chemo/PTT platform. The HMSNs-CS-DOX@CuS nanoparticles have a uniform size (150 ± 13 nm), potent photothermal properties (η = 36.4 %), and tumor-targeted and near infrared (NIR) laser irradiation-triggered DOX release. In vitro and in vivo experimental results confirmed that the material has good biocompatibility, but is effectively taken up by cancer cells. Moreover, the CuS nanodots permit simultaneous thermal/photoacoustic dual-modality imaging. Treatment with HMSNs-CS-DOX@CuS and NIR irradiation caused extensive apoptosis in cancer cells both in vitro and in vivo, and could dramatically extend the lifetimes of animals in a murine breast cancer model. The system developed in this work therefore merits further investigation as a potential nanotheranostic platform for cancer treatment. STATEMENT OF SIGNIFICANCE: Conventional cancer chemotherapy is accompanied by unavoidable off-target toxicity. Combination therapies, which can ameliorate these issues, are attracting significant attention. Here, the anticancer drug doxorubicin (DOX) was encapsulated in the central cavity of chitosan (CS)-modified hollow mesoporous silica nanoparticles (HMSNs). The prepared system can target drug release to the tumor microenvironment. When exposed to near infrared laser (NIR) irradiation, CuS nanodots located at the surface pores of the HMSNs generate energy, accelerating drug release. In addition, a systematic in vitro and in vivo evaluation confirmed the HMSNs-CS-DOX@CuS platform to give highly effective synergistic chemotherapeutic-photothermal therapy and have effective thermal/photoacoustic dual-imaging properties. This work may open up a new avenue for NIR-enhanced synergistic therapy with simultaneous thermal/photoacoustic dual imaging.
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http://dx.doi.org/10.1016/j.actbio.2021.03.024DOI Listing
May 2021

Prolactin Is Associated With Insulin Resistance and Beta-Cell Dysfunction in Infertile Women With Polycystic Ovary Syndrome.

Front Endocrinol (Lausanne) 2021 25;12:571229. Epub 2021 Feb 25.

Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: Our study aimed to investigate if serum prolactin (PRL) levels associated with insulin resistance and beta-cell dysfunction in infertile patients with polycystic ovary syndrome (PCOS).

Methods: This was a retrospective cross-sectional study performed in the reproductive medicine center of the first affiliated hospital of Wenzhou Medical University. From January 2007 to August 2018, a total of 792 PCOS and 700 non-PCOS infertile women were included. All patients' prolactin levels were in the normal range. PCOS was diagnosed according to the Rotterdam Criteria. Anthropometric parameters, blood pressure, serum prolactin levels, sex hormones, fasting lipids, fasting plasma glucose (FPG), fasting insulin (FINS) and hepatic biological parameters were measured in all subjects.

Results: Serum prolactin levels in PCOS women were significantly decreased compared with levels in non-PCOS women after adjusting for age and BMI ( < 0.05). Moreover, we found that prolactin levels were positively associated with high-density lipoprotein cholesterol (HDL-C) and negatively associated with age, BMI, waist circumference (WC), hip circumference (HC), luteinizing hormone/follicle stimulating hormone (LH/FSH), estradiol (E), FINS, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of β (HOMA-β), triglyceride (TG) and alanine aminotransferase (ALT) ( < 0.05). After adjusting for age and BMI, multiple linear regression analysis revealed that LH, LH/FSH, E, FINS, HOMA-IR, and HOMA-β were negatively associated with serum PRL ( < 0.05).

Conclusions: Low serum PRL levels within the normal range associates with a higher incidence of insulin resistance and beta-cell dysfunction in infertile women with PCOS.
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http://dx.doi.org/10.3389/fendo.2021.571229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947819PMC
February 2021

Effect of Cisplatin Arterial Infusion (CAI) on Primary Nonmetastatic Pelvic Osteosarcoma: A Preliminary Study.

Cancer Manag Res 2021 15;13:1491-1503. Epub 2021 Feb 15.

Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People's Republic of China.

Purpose: The critical role of arterial infusion chemotherapy in the multimodal treatment of extremity bone cancer has been investigated extensively, but few studies have focused on pelvic osteosarcoma. Therefore, we attempted to evaluate the clinical significance of arterial infusion chemotherapy in the treatment of pelvic osteosarcoma.

Patients And Methods: We combined a cisplatin arterial infusion regimen with multidrug systematic chemotherapy as a neoadjuvant protocol for the treatment of pelvic osteosarcoma. The course number and dosage of cisplatin arterial infusion were adjusted to achieve a maximal tumor response evaluated by contrast-enhanced MRI per RECIST 1.1. Good responders received the same systematic combination for postoperative chemotherapy, and poor responders received second-line therapy. Twelve patients with nonmetastatic high-grade pelvic osteosarcoma were included. Survival, chemotherapy response and adverse events data were analyzed.

Results: The mean follow-up period was 56.1 months. Four patients died of refractory tumor progression, and 1 patient with local recurrence had no evidence of disease for 27 months after receiving secondary amputation and resection. Kaplan-Meier survival analysis demonstrated a 57.8% overall survival and 52.5% event-free survival rate at 5 years. Eight of 12 patients had a >90% tumor necrosis rate according to histopathologic examinations. The rates of local adverse events were lower than those reported for extremity osteosarcoma.

Conclusion: Our study initially indicated that the cisplatin arterial infusion regimen was a potential therapy with good tolerance in the treatment of pelvic osteosarcoma.
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http://dx.doi.org/10.2147/CMAR.S294677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894794PMC
February 2021

Lacking Communication Would Increase General Symptom Index Scores of Medical Team Members During COVID-19 Pandemic in China: A Retrospective Cohort Study.

Inquiry 2021 Jan-Dec;58:46958021997344

The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, Anhui Province, People's Republic of China.

There are few studies on the psychological status of medical staff during the COVID-19 outbreak. Our study addresses whether lack of communication affects the psychological status of medical team members supporting Wuhan during the COVID-19 pandemic in China. We used general symptom index (GSI) scores of the Symptom Checklist-90 (SCL-90) to evaluate participants' psychological status. We adopted a stratified sampling method and selected the fourth team, with a total of 137 members, as participants. In total 76.6% and 69.7% of female and male participants, respectively, had bachelor's degrees; 41.6% and 21.2% of female and male participants, respectively, were unmarried. Regarding communication, 14.29% and 6.06% of female and male participants, respectively, reported a lack of communication with the team (LCWT). Additionally, 13.0% and 6.1% of female and male participants, respectively, experienced fear of being infected (FoBI). LCWT and FoBI were positively correlated with GSI score (estimated change = 0.2, 95% CI [0.1-0.3]). When adjusted for gender, age, and FoBI, LCWT was positively correlated with GSI score ( < .05). Increasing communication among medical team members can reduce GSI scores.
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http://dx.doi.org/10.1177/0046958021997344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905727PMC
March 2021

Efficient endothelial and smooth muscle cell differentiation from human pluripotent stem cells through a simplified insulin-free culture system.

Biomaterials 2021 Apr 11;271:120713. Epub 2021 Feb 11.

Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing, 100084, China. Electronic address:

A major obstacle for using human pluripotent stem cells (hPSCs) derived vascular cells for cell therapy is the lack of simple, cost-saving, and scalable methods for cell production. Here we described a simplified and chemically defined medium (AATS) for endothelial cells (ECs) and smooth muscle cells (SMCs) differentiation. AATS medium does not contain insulin, enabling the rapid and highly efficient vascular mesoderm formation through accelerating metabolic and autophagy-enhanced mesoderm induction. Transcriptome profiling confirmed that hPSC-derived ECs and SMCs in the AATS medium closely resembled primary ECs and SMCs formed in vivo. ECs appeared to adhere and grow better in the AATS medium over other cell types, which allowed the purification of CD31CD144 double-positive cells. Furthermore, the AATS medium was compatible with 3D microscaffold (MS) culture, which may facilitate large-scale bioproduction of ECs. HPSC-derived ECs and SMCs in the AATS medium exhibited strong revascularization potential in treating murine ischemic models. Our study provided a cost-effective and efficient medium system to manufacture GMP compatible, off-the-shelf ECs, and SMCs to model human diseases and vascular repair.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120713DOI Listing
April 2021

Tissue-engineered autologous peritoneal grafts for bladder reconstruction in a porcine model.

J Tissue Eng 2021 Jan-Dec;12:2041731420986796. Epub 2021 Feb 6.

School of Clinical Medicine, Tsinghua University, Beijing, China.

Ileal neobladder construction is a common treatment for patients with bladder cancer after radical cystectomy. However, metabolic disorders caused by transposed bowel segments occur frequently. Bladder tissue engineering is a promising alternative approach. Although numerous studies have reported bladder reconstruction using acellular and cellular scaffolds, there are also disadvantages associated with these methods, such as immunogenicity of synthetic grafts and incompatible mechanical properties of the biomaterials. Here, we engineered an autologous peritoneal graft consisting of a peritoneal sheet and the seromuscular layer from the ileum. Three months after the surgery, compared with the neobladder made from the ileum, the reconstructed neobladder using our new method showed normal function and better gross morphological characteristics. Moreover, histopathological and transcriptomic analysis revealed urothelium-like cells expressing urothelial biomarkers appeared in the neobladder, while no such changes were observed in the control group. Overall, our study provides a new strategy for bladder tissue engineering and informs a variety of future research prospects.
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http://dx.doi.org/10.1177/2041731420986796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874343PMC
February 2021

The Genome of Banana Leaf Blight Pathogen str. FS66 Harbors Widespread Gene Transfer From .

Front Plant Sci 2021 4;12:629859. Epub 2021 Feb 4.

Guangdong Provincial Key Laboratory of High Technology for Plant Protection, Plant Protection Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, China.

species have been identified as pathogens causing many different plant diseases, and here we report an emerging banana leaf blight (BLB) caused by () discovered in Guangdong, China. From the symptomatic tissues collected in the field, a fungal isolate was obtained, which induced similar symptoms on healthy banana seedlings after inoculation. Koch's postulates were fulfilled after the re-isolation of the pathogen. Phylogenetic analysis on two gene segments and the whole genome sequence identified the pathogen belonging to and named as str. FS66. A 45.74 Mb genome of FS66 was acquired through assembly using long-read sequencing data, and its contig N50 (1.97 Mb) is more than 10-fold larger than the previously available genome in the species. Based on transcriptome sequencing and gene annotation, a total of 14,486 protein-encoding genes and 418 non-coding RNAs were predicted. A total of 48 metabolite biosynthetic gene clusters including the fusaric acid biosynthesis gene cluster were predicted in the FS66 genome. Comparison between FS66 and other 11 Fusarium genomes identified tens to hundreds of genes specifically gained and lost in FS66, including some previously correlated with pathogenicity. The FS66 genome also harbors widespread gene transfer on the core chromosomes putatively from species complex (FOSC), including 30 involved in pathogenicity/virulence. This study not only reports the BLB caused by , but also provides important information and clues for further understanding of the genome evolution among pathogenic species.
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http://dx.doi.org/10.3389/fpls.2021.629859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889605PMC
February 2021