Publications by authors named "Hu Zhao"

379 Publications

Genome- and transcriptome-wide association studies reveal the genetic basis and the breeding history of seed glucosinolate content in Brassica napus.

Plant Biotechnol J 2021 Sep 15. Epub 2021 Sep 15.

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

A high content of seed glucosinolates (GSLs) and their degradation products impose anti-nutritional effects on livestock; therefore, persistent efforts are made to reduce the seed GSL content to increase the commercial value of rapeseed meal. Here, we dissected the genetic structure of SGC by genome-wide association studies (GWAS) combined with transcriptome-wide association studies (TWAS). Fifteen reliable QTLs were identified to be associated with the reduced SGC in modern B. napus cultivars by GWAS. Analysis of the selection strength and haplotypes at these QTLs revealed that low SGC was predominantly generated by the co-selection of qGSL.A02.2, qGSL.C02.1, qGSL.A09.2, and qGSL.C09.1. Integration of the results from TWAS, comprehensive bioinformatics, and POCKET algorithm analyses indicated that BnaC02.GTR2 (BnaC02g42260D) is a candidate gene underlying qGSL.C02.1. Using CRISPR/Cas9 derived Bna.gtr2s knockout mutants, we experimentally verified that both BnaC02.GTR2 and its three paralogs positively regulate seed GSL accumulation but negatively regulated vegetative tissue GSL contents. In addition, we observed smaller seeds with higher seed oil content in these Bna.gtr2 mutants. Furthermore, both RNA-seq and correlation analyses suggested that Bna.GTR2s might play a comprehensive role in seed development, such as amino acid accumulation, GSL synthesis, sugar assimilation, and oil accumulation. This study unravels the breeding selection history of low SGC improvement and provides new insights into the molecular function of Bna.GTR2s in both seed GSL accumulation and seed development in B. napus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pbi.13707DOI Listing
September 2021

A New Multiplex Genetic Detection Assay Method for the Rapid Semi-Quantitative Detection of Six Common Curable Sexually Transmitted Pathogens From the Genital Tract.

Front Cell Infect Microbiol 2021 23;11:704037. Epub 2021 Aug 23.

Department of Laboratory Medicine, Huadong Hospital, Affiliated With Fudan University, Shanghai, China.

Background: Sexually transmitted infections (STIs) are some of the most common communicable conditions and exert impact on the health and lives of many hundreds of millions of people across the world every year. Screening high-risk populations and conducting comprehensive detection tests would lead to a significant improvement in preventing the transmission of STIs and help us to provide rapid treatment to those affected. Here, we successfully established and validated a novel high-throughput multiplex gene detection system (HMGS) for the simultaneous and semiquantitative detection of six important curable sexually transmitted pathogens in a single reaction from secretions samples.

Method: Fluorescently labeled primers were designed to target specific conserved and single-copy gene fragments of Ureaplasma urealyticum (U. urealyticum), Mycoplasma hominis (), Chlamydia trachomatis (), Neisseria gonorrhoeae (), Trichomonas vaginalis (), and Treponema pallidum (). The specificity and sensitivity of the STI-HMGS was validated and optimized using plasmids and quantitative genomic DNA. Next, we validated the performances of the STI-HMGS for clinical application by testing samples of clinical secretions collected from patients who visited the gynecology and urology outpatient clinics of our reproductive medicine center. Results derived from the STI-HMGS were then compared with three approved commercialized kits that used to detect and , respectively, followed by further validation with Sanger sequencing for all pathogens. Finally, a comprehensive analysis of epidemiology was performed among different subgroups to investigate the association between infection rates and clinically-relevant information.

Results: The sensitivity of STI-HMGS for six target genes was 10 copies/µL. Data derived from the detection of 381 clinical secretions demonstrated that the STI-HMGS exhibited high concordance rate compared with approved commercialized kits and almost 100% sensitivity and specificity for the detection of six sexually transmitted pathogens when validated by Sanger sequencing. Semi-quantitative analysis found that STIs caused by had a significantly higher () pathogen load than the other pathogens. Infections caused by were significantly more common in younger individuals (). We also found that infections were more likely to happen in females; while the males were more affected by (P<0.05).

Conclusions: STI-HMGS proved to be an efficient method for the semi-quantitative detection of six important curable sexually transmitted pathogens and therefore represents an alternative method for the clinical detection and monitoring of STIs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2021.704037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420868PMC
August 2021

Deciphering the Shifts in Microbial Community Diversity From Material Pretreatment to Saccharification Process of -Flavor .

Front Microbiol 2021 20;12:705967. Epub 2021 Aug 20.

Nutrition & Health Research Institute, COFCO Corporation, Beijing, China.

The microbiota of the pretreatment phase is crucial to the assembly of the microbial community in the saccharification of -flavor . This study investigates the shifts in microbial community diversity from the pretreatment of raw materials to the end of saccharification. High-throughput sequencing reveals that , , and in the bacterial community and , , , and in the fungal community are predominant during raw material pretreatment and saccharification processes. Also, 11 bacterial genera, including , , , , , and , and eight yeast genera, including , , , and , were isolated from the initial saccharification stage by culture-dependent approaches. Sourcetracker analysis indicates that the cooling grains and rice husks were the main contributors to the bacterial community composition of the saccharification process, and was the main contributor to the shaping of the fungal community structure during the saccharification process. Abundance variation of the predictive functional profiles of microbial communities encoding for key enzymes involved in pyruvate metabolism, starch and sucrose metabolism, and glycolysis/gluconeogenesis during the pretreatment and saccharification phases were inferred by PICRUSt2 analysis. The results of this study will be utilized to produce consistently high-quality -flavor via better controlling the shaping of microbial community structures during the pretreatment and fermentation processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.705967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417803PMC
August 2021

Tissue Clearing and 3-D Visualization of Vasculature with the PEGASOS Method.

Methods Mol Biol 2021 ;2319:1-13

Department of Comprehensive Dentistry, Texas A&M University College of Dentistry, Dallas, Texas, USA.

Tissue clearing techniques turn tissue transparent through a series of chemical and physical treatments. They have provided a useful tool for three-dimensional (3-D) imaging to study tissue spatial organization and interactions. Many tissue clearing methods have been developed in recent years. Each method has its own application range depending on the purposes of the study. Three criteria for selecting an appropriate clearing method include clearing transparency, fluorescence preservation, and broad tissue applicability. PEG-associated solvent system (PEGASOS) emerged recently as a solvent-based tissue clearing method capable of rendering diverse tissues highly transparent while preserving fluorescence. Combined with vascular labeling techniques, PEGASOS method enables 3-D visualization of vasculature in whole tissues at subcellular resolution. Here, we describe the standard PEGASOS passive immersion protocol and several compatible vascular labeling techniques. Methods of 3-D imaging, data processing, and annotations are also briefly introduced.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-0716-1480-8_1DOI Listing
August 2021

Osteocytes but not osteoblasts directly build mineralized bone structures.

Int J Biol Sci 2021 11;17(10):2430-2448. Epub 2021 Jun 11.

Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX 75246, USA.

Bone-forming osteoblasts have been a cornerstone of bone biology for more than a century. Most research toward bone biology and bone diseases center on osteoblasts. Overlooked are the 90% of bone cells, called osteocytes. This study aims to test the hypothesis that osteocytes but not osteoblasts directly build mineralized bone structures, and that defects in osteocytes lead to the onset of hypophosphatemia rickets. The hypothesis was tested by developing and modifying multiple imaging techniques, including both and models plus two types of hypophosphatemia rickets models (-null and Hyp, Phex mutation mice), and -Cre induced high level of β-catenin models. Our key findings were that osteocytes (not osteoblasts) build bone similar to the construction of a high-rise building, with a wire mesh frame (i.e., osteocyte dendrites) and cement (mineral matrices secreted from osteocytes), which is a lengthy and slow process whose mineralization direction is from the inside toward the outside. When osteoblasts fail to differentiate into osteocytes but remain highly active in -1-null or Hyp mice, aberrant and poor bone mineralization occurs, caused by a sharp increase in Wnt-β-catenin signaling. Further, the constitutive expression of β-catenin in osteocytes recaptures a similar osteomalacia phenotype as shown in null or mice. Thus, we conclude that osteocytes directly build bone, and osteoblasts with a short life span serve as a precursor to osteocytes, which challenges the existing dogma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijbs.61012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315029PMC
June 2021

The Role of TRPC6 in Renal Ischemia/Reperfusion and Cellular Hypoxia/Reoxygenation Injuries.

Front Mol Biosci 2021 8;8:698975. Epub 2021 Jul 8.

Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Renal ischemia/reperfusion (I/R), a major cause of acute kidney injury (AKI), is a serious clinical event in patients during post-renal transplantation. I/R is associated with renal dysfunction and tubular apoptosis, and calcium (Ca) overload has been reported to be a crucial factor on tubular apoptosis in I/R injury (IRI). The canonical transient receptor potential channel 6 (TRPC6), a type of non-selective Ca channel, is involved in many renal diseases. Our earlier study identified that TRPC6-mediated Ca influx plays a novel role in suppressing cytoprotective autophagy triggered by oxidative stress in primary tubular epithelial cells (TECs). This study explored the potential beneficial impact of TRPC6 knockout (TRPC6) and the relevant cellular mechanisms against I/R-induced AKI in mice. Measuring changes of renal function, apoptotic index, and autophagy in mouse kidneys that suffered 24 h reperfusion after 40 min ischemia and working with TECs that suffered 24 h reoxygenation after 24 h hypoxia, we found that 1) IRI tissues had increased TRPC6 expression and TRPC6 knockout significantly ameliorated renal damage induced by IRI; 2) TRPC6 knockout enhanced the level of autophagy and alleviated the depolarization of mitochondrial membrane potential (ψm, MMP) and apoptotic changes upon IRI; and 3) IRI tissues had increased p-AKT and p-ERK1/2 expressions, while TRPC6 knockout could markedly reduce the phosphorylation of AKT and ERK1/2. These discoveries suggest that, by reducing Ca overload, the underlying protective mechanism of TRPC6 may be involved in down-regulation of PI3K/AKT and ERK signaling, which is likely to provide a new avenue for future AKI therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2021.698975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295989PMC
July 2021

Efficacy and Safety of Leflunomide for Refractory COVID-19: A Pilot Study.

Front Pharmacol 2021 2;12:581833. Epub 2021 Jul 2.

Department of Nephropathy, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may persist in patients with coronavirus disease 2019 (COVID-19) despite receiving standard care. In this pilot study of hospitalized adult patients (≥18 years of age), with radiologically confirmed pneumonia who were SARS-CoV-2 positive for more than 28 days despite standard care, were assigned to receive standard of care (SOC, grp I) or leflunomide + SOC (grp 2). After 2 weeks, grp 1 and grp 2 patients who continued to be SARS-CoV-2-positive received leflunomide for 14 days while continuing SOC. The primary outcomes were the rate of and time to SARS-CoV-2 clearance and the 14-day and 30-day hospital discharge rate. 12 patients were enrolled in grp 1 and 15 patients were in grp 2. The 14 days SARS-CoV-2 viral clearance rate was 80.0% (12/15) for grp 2 patients receiving leflunomide 16.7% for grp 1 patients (2/12) ( = 0.002). By day 14, the median time to SARS-CoV-2 clearance was 6.0 days (range 1-12, IQR 1-12) for grp 2 patients. In grp 1, two patients converted to viral negative on days 1 and 6 ( 0.002). The 14-day discharge rate was 73.3% (11/15) for the grp 2 vs. 8.3% (1/12) for grp 1 ( 0.001). The 30 days discharge rate was 100% (15/15) for the grp 2 vs. 66.7% (8/12) for grp 1. No severe adverse events or deaths were reported. Leflunomide may improve the SARS-CoV-2 clearance rate and discharge rate in patients with refractory COVID-19. The tolerability of the 14-28 days course of treatment with leflunomide is acceptable. These preliminary observations need to be verified by a large sample size and randomized controlled trial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.581833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284962PMC
July 2021

First Report of Colletotrichum cliviicola Causing Leaf Spot on Tobacco (Nicotiana tabacum) in Hunan Province of China.

Plant Dis 2021 Jul 16. Epub 2021 Jul 16.

Hunan Provincial Key Laboratory for Biology and Control of Plant Diseases and Insect Pests, Hunan Agricultural University, Nongda Road 1, Furong District, Changsha City, Hunan Province, Changsha, China;

Tobacco (Nicotiana tabacum L.) is an annual, leafy, herb of the genus Nicotiana in the family Solanaceae. It is an important commercial crop in China. In 2020, a leaf spot disease was observed on tobacco leaves in commercial fields in the Hunan Province of China. Symptoms appeared as water-soaked, yellow-green spots, then turned dark brown, and coalesced into larger necrotic lesions, often leading to leaf wilt. Approximately 20% of the plants in a 50-ha area were infected, exhibiting symptomatic spots on 60% of these leaves. Symptomatic leaf samples were collected and cut into small pieces, sterilized with 70% ethanol for 10 s, 0.1% HgCl2 for 40s, rinsed with sterile distilled water for three times, plated on potato dextrose agar (PDA) and incubated at 26°C in the dark. Isolates with similar morphology were developed from ten samples. Fungal isolates produced densely, white to dark green, aerial mycelium. Conidia were straight, hyaline, aseptate, cylindrical, contained oil globules, and 15 to 25 µm × 3.0 to 4.0 µm (n=50). Appressoria were dark brown, irregularly shaped, 5.5 to 10.0 μm × 4.5 to 6.5 μm (n=50). These morphological characteristics were typical of Colletotrichum cliviicola (Yang et al. 2009). For molecular identification, the internal transcribed spacer (ITS) region of rDNA, actin (ACT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and chitin synthase (CHS-1) genes of a representative isolate CS16-2 were amplified and sequenced using the primer pairs as described previously (Weir et al. 2012). These sequences were deposited in GenBank (GenBank Accession Nos. MW649137 for ITS, MW656181 for ACT, MW656182 for GAPDH and MW656183 for CHS-1). BLAST analysis showed that they had 99.46% to 100% identity to the corresponding sequences of C. cliviicola strains. A concatenated phylogenetic tree was generated, using the ACT, GAPDH and CHS-1 sequences of the isolate CS16-2 and other closely matching Colletotrichum species obtained from the GenBank. We found that the CS16-2 was grouped with the C. cliviicola clade with 97% bootstrap support, including the C. cliviicola strain AH1B6 (Wang et al. 2016). Pathogenicity was tested spraying 2-month-old potted tobacco plants until runoff with a conidial suspension (105 spores/ml). Leaves were mock inoculated with sterilized water. The pathogenicity tests were performed twice, with three replicate plants each. Plants were kept in humid chambers at 26°C with a 12-h photoperiod. Five days post-inoculation, the inoculated plants developed symptoms of consisting of the yellow-brown necrotic lesion resembling the symptoms that were observed in fields, while the control plants remained symptomless. C. cliviicola was re-isolated and identified by morphological and molecular methods as described above. Currently, C. cliviicola has been reported to be the causal agent of anthracnose in some plants, such as soybean (Zhou et al. 2017) and Zamioculcas zamiifolia (Barbieri et al. 2017). However, to our knowledge, this is the first report of C. cliviicola causing leaf spot on tobacco in China and even in the word. Given that the may greatly affect the yield and quality of tobacco production, growers should be prepared to manage this new disease. This work might provide further insight for disease diagnosis on tobacco as some other Colletotrichum species, such as C. fructicola (Wang et al. 2016) and C. karsti (Zhao et al. 2020), have also been responsible for anthracnose.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1094/PDIS-02-21-0409-PDNDOI Listing
July 2021

A Novel Partitivirus That Confer Hypovirulence to the Plant Pathogenic Fungus .

Front Microbiol 2021 22;12:653809. Epub 2021 Jun 22.

Hunan Provincial Key Laboratory for Biology and Control of Plant Diseases and Insect Pests, Hunan Agricultural University, Changsha, China.

Here, we report a novel double-stranded RNA virus designated Colletotrichum liriopes partitivirus 1 (ClPV1) from the plant pathogenic fungus ClPV1 genome has two double stranded RNAs (dsRNAs), named as dsRNA 1 and dsRNA 2, which in the lengths of 1,807 and 1,706 bp, respectively. The dsRNA 1 and dsRNA 2 encoded proteins showing significant amino acid (aa) sequence identity to the RNA-dependent RNA polymerase (RdRp) and coat protein (CP) of partitiviruses, respectively. Phylogenetic analysis using the aa sequences of RdRp and CP indicated that ClPV1 was grouped to members of the putative Epsilonpartitivirus genus in the family. Spherical viral particles in approximately 35 nm in diameter and packaging the ClPV1 genome were isolated. Virus elimination and virus transfection with purified viral particles, and biological comparison revealed that ClPV1 could reduce the virulence and conidia production of . To the best of our knowledge, this is the first report of mycovirus in fungus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.653809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262616PMC
June 2021

An inferred functional impact map of genetic variants in rice.

Mol Plant 2021 Sep 29;14(9):1584-1599. Epub 2021 Jun 29.

National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, China; Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan, China. Electronic address:

Interpreting the functional impacts of genetic variants (GVs) is an important challenge for functional genomic studies in crops and next-generation breeding. Previous studies in rice (Oryza sativa) have focused mainly on the identification of GVs, whereas systematic functional annotation of GVs has not yet been performed. Here, we present a functional impact map of GVs in rice. We curated haplotype information for 17 397 026 GVs from sequencing data of 4726 rice accessions. We quantitatively evaluated the effects of missense mutations in coding regions in each haplotype based on the conservation of amino acid residues and obtained the effects of 918 848 non-redundant missense GVs. Furthermore, we generated high-quality chromatin accessibility (CA) data from six representative rice tissues and used these data to train deep convolutional neural network models to predict the impacts of 5 067 405 GVs for CA in regulatory regions. We characterized the functional properties and tissue specificity of the GV effects and found that large-effect GVs in coding and regulatory regions may be subject to selection in different directions. Finally, we demonstrated how the functional impact map could be used to prioritize causal variants in mapping populations. This impact map will be a useful resource for accelerating gene cloning and functional studies in rice, and can be freely queried in RiceVarMap V2.0 (http://ricevarmap.ncpgr.cn).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molp.2021.06.025DOI Listing
September 2021

OsCBL1 affects rice seedling growth by modulating nitrate and phosphate responses.

Gene 2021 Sep 29;796-797:145806. Epub 2021 Jun 29.

Key Laboratory of Molecular Biology and Gene Engineering of Jiangxi Province, College of Life Science, Nanchang University, Nanchang 330031, China. Electronic address:

To sustain high crop yield, a comprehensive understanding of the processes by which plants sense and acquire nutrients is of great importance. For the efficiency of crop fertilizer, it is essential to exploring the the signaling networks that coordinate the usage of nitrogen and phosphorus, the most demanding two mineral nutrients in plants. Here, we found that a protein OsCBL1 (Calcineurin B-like protein 1) is involved in the regulation of nitrogen and phosphorus signaling in rice. The nitrogen element, existing as ammonium or nitrate in the environment, affects nitrate signaling in vivo and root growth. Compared with the wild type, knockdown of OsCBL1 inhibit the growth of rice to the same extent, when nitrogen is deficient or nitrogen is present in the form of ammonium-nitrate mixture. The growth inhibition by OsCBL1-knockdown is more pronounced when nitrogen is present as ammonium. The phosphorus starvation-responsive genes is also regulated by the compound of nitrogen present in vitro and OsCBL1, while the phosphorus content is not affected. These results suggest that OsCBL1 may be involved in the response of rice to nitrogen and phosphorus nutrition in the environment, as well as the regulation of rice growth by environmental nutrition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2021.145806DOI Listing
September 2021

Fangchinoline Inhibits Human Esophageal Cancer by Transactivating ATF4 to Trigger Both Noxa-Dependent Intrinsic and DR5-Dependent Extrinsic Apoptosis.

Front Oncol 2021 14;11:666549. Epub 2021 Jun 14.

Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Esophageal squamous cell carcinoma (ESCC) is a recalcitrant cancer. The Chinese herbal monomer fangchinoline (FCL) has been reported to have anti-tumor activity in several human cancer cell types. However, the therapeutic efficacy and underlying mechanism on ESCC remain to be elucidated. In the present study, for the first time, we demonstrated that FCL significantly suppressed the growth of ESCC both and . Mechanistic studies revealed that FCL-induced G1 phase cell-cycle arrest in ESCC which is dependent on p21 and p27. Moreover, we found that FCL coordinatively triggered Noxa-dependent intrinsic apoptosis and DR5-dependent extrinsic apoptosis by transactivating ATF4, which is a novel mechanism. Our findings elucidated the tumor-suppressive efficacy and mechanisms of FCL and demonstrated FCL is a potential anti-ESCC agent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.666549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236818PMC
June 2021

Combining UAV-RGB high-throughput field phenotyping and genome-wide association study to reveal genetic variation of rice germplasms in dynamic response to drought stress.

New Phytol 2021 10 23;232(1):440-455. Epub 2021 Jul 23.

Macro Agriculture Research Institute, College of Resource and Environment, Huazhong Agricultural University, Wuhan, 430070, China.

Accurate and high-throughput phenotyping of the dynamic response of a large rice population to drought stress in the field is a bottleneck for genetic dissection and breeding of drought resistance. Here, high-efficiency and high-frequent image acquisition by an unmanned aerial vehicle (UAV) was utilized to quantify the dynamic drought response of a rice population under field conditions. Deep convolutional neural networks (DCNNs) and canopy height models were applied to extract highly correlated phenotypic traits including UAV-based leaf-rolling score (LRS_uav), plant water content (PWC_uav) and a new composite trait, drought resistance index by UAV (DRI_uav). The DCNNs achieved high accuracy (correlation coefficient R = 0.84 for modeling set and R = 0.86 for test set) to replace manual leaf-rolling rating. PWC_uav values were precisely estimated (correlation coefficient R = 0.88) and DRI_uav was modeled to monitor the drought resistance of rice accessions dynamically and comprehensively. A total of 111 significantly associated loci were detected by genome-wide association study for the three dynamic traits, and 30.6% of them were not detected in previous mapping studies using nondynamic drought response traits. Unmanned aerial vehicle and deep learning are confirmed effective phenotyping techniques for more complete genetic dissection of rice dynamic responses to drought and exploration of valuable alleles for drought resistance improvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/nph.17580DOI Listing
October 2021

Abiotic and Biotic Influences on the Movement of Reintroduced Chinese Giant Salamanders () in Two Montane Rivers.

Animals (Basel) 2021 May 21;11(6). Epub 2021 May 21.

Department of Wildlife, Fisheries and Aquaculture, Mississippi State University, Starkville, MS 39762, USA.

Understanding animal movement is a key question in ecology and biodiversity conservation, which is particularly important for the success of reintroduction projects. The movement of critically endangered Chinese giant salamander () remains poorly understood due to the rareness of wild individuals of this species. We lack movement details about the full annual cycle after reintroduction, especially the abiotic and biotic influences that affect its movement. We utilized pilot reintroduction projects as opportunities to fill in some knowledge gaps on their movement ecology. We released 31 juvenile captive-reared Chinese giant salamanders of two age groups in two rivers in the Qinling Mountains of central China and monitored their daily movements for 16 months using surgically implanted radio transmitters. We examined the impacts of individual traits (body mass, body condition) and environmental conditions (temperature, precipitation, and moon phase) on their daily movement patterns. Data were analyzed using a mixed-effects logistic regression model to understand the drivers of their movement tendency (i.e., whether they move or not) and a linear mixed-effects model was used to understand the drivers of their movement distance. We found that movement tendency of the older salamander cohort was positively affected by the moon phase, increasing near the Full Moon, whereas the younger cohort of animals were not impacted by the moon phase. For daily distance moved, we found temperature had a strong positive effect on both cohorts, whereas precipitation had moderate but opposite effects on the two cohorts Body mass and body condition did not have any significant impacts on either age classes' movement tendency or distance. This study provides insight into the abiotic factors that impact the temporal and spatial movement ecology of reintroduced giant salamander, which will in turn help with designing best practices for future releases and conservation of this iconic montane aquatic predator.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ani11061480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224018PMC
May 2021

PlantDeepSEA, a deep learning-based web service to predict the regulatory effects of genomic variants in plants.

Nucleic Acids Res 2021 07;49(W1):W523-W529

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

Characterizing regulatory effects of genomic variants in plants remains a challenge. Although several tools based on deep-learning models and large-scale chromatin-profiling data have been available to predict regulatory elements and variant effects, no dedicated tools or web services have been reported in plants. Here, we present PlantDeepSEA as a deep learning-based web service to predict regulatory effects of genomic variants in multiple tissues of six plant species (including four crops). PlantDeepSEA provides two main functions. One is called Variant Effector, which aims to predict the effects of sequence variants on chromatin accessibility. Another is Sequence Profiler, a utility that performs 'in silico saturated mutagenesis' analysis to discover high-impact sites (e.g., cis-regulatory elements) within a sequence. When validated on independent test sets, the area under receiver operating characteristic curve of deep learning models in PlantDeepSEA ranges from 0.93 to 0.99. We demonstrate the usability of the web service with two examples. PlantDeepSEA could help to prioritize regulatory causal variants and might improve our understanding of their mechanisms of action in different tissues in plants. PlantDeepSEA is available at http://plantdeepsea.ncpgr.cn/.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gkab383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262748PMC
July 2021

First Report of Leaf Spot Caused by Botrytis cinerea on Cardamine hupingshanensis in China.

Plant Dis 2021 May 24. Epub 2021 May 24.

Hunan Provincial Key Laboratory for Biology and Control of Plant Diseases and Insect Pests, Hunan Agricultural University, Nongda Road 1, Furong District, Changsha City, Hunan Province, Changsha, China;

Cardamine hupingshanensis is a selenium (Se) and cadmium (Cd) hyperaccumulator plant distributed in wetlands along the Wuling Mountains of China (Zhou et al. 2018). In March of 2020, a disease with symptoms similar to gray mold was observed on leaves of C. hupingshanensis in a nursery located in Changsha, Hunan Province, China. Almost 40% of the C. hupingshanensis (200 plants) were infected. Initially, small spots were scattered across the leaf surface or margin. As disease progressed, small spots enlarged to dark brown lesions, with green-gray, conidia containing mold layer under humid conditions. Small leaf pieces were cut from the lesion margins and were sterilized with 70% ethanol for 10 s, 2% NaOCl for 2 min, rinsed with sterilized distilled water for three times, and then placed on potato dextrose agar (PDA) medium at 22°C in the dark. Seven similar colonies were consistently isolated from seven samples and further purified by single-spore isolation. Strains cultured on PDA were initially white, forming gray-white aerial mycelia, then turned gray and produced sclerotia after incubation for 2 weeks, which were brown to blackish, irregular, 0.8 to 3.0 × 1.2 to 3.5 mm (n=50). Conidia were unicellular, globose or oval, colourless, 7.5 to 12.0 × 5.5 to 8.3 μm (n=50). Conidiophores arose singly or in group, straight or flexuous, septate, brownish to light brown, with enlarged basal cells, 12.5 to 22.1 × 120.7 to 310.3 μm. Based on their morphological characteristics in culture, the isolates were putatively identified as Botrytis cinerea (Ellis 1971). Genomic DNA of four representative isolates, HNSMJ-1 to HNSMJ-4, were extracted by CTAB method. The internal transcribed spacer region (ITS), glyceraldehyde-3-phosphate dehydrogenase gene (G3PDH), heat-shock protein 60 gene (HSP60), ATP-dependent RNA helicaseDBP7 gene (MS547) and DNA-dependent RNA polymerase subunit II gene (RPB2) were amplified and sequenced using the primers described previously (Aktaruzzaman et al. 2018) (MW820311, MW831620, MW831628, MW831623 and MW831629 for HNSMJ-1; MW314722, MW316616, MW316617, MW316618 and MW316619 for HNSMJ-2; MW820519, MW831621, MW831627, MW831624 and MW831631 for HNSMJ-3; MW820601, MW831622, MW831626, MW831625 and MW831630 for HNSMJ-4). BLAST searches showed 99.43 to 99.90% identity to the corresponding sequences of B. cinerea strains, such as HJ-5 (MF426032.1, MN448500.1, MK791187.1, MH727700.1 and KX867998.1). A combined phylogenetic tree using the ITS, G3PDH, HSP60 and RPB2 sequences was constructed by neighbor-joining method in MEGA 6. It revealed that HNSMJ-1 to HNSMJ-4 clustered in the B. cinerea clade. Pathogenicity tests were performed on healthy pot-grown C. hupingshanensis plants. Leaves were surface-sterilized and sprayed with conidial suspension (106 conidia/ mL), with sterile water served as controls. All plants were kept in growth chamber with 85% humidity at 25℃ following a 16 h day-8 h night cycle. The experiment was repeated twice, with each three replications. After 4 to 7 days, symptoms similar to those observed in the field developed on the inoculated leaves, whereas controls remained healthy. The pathogen was reisolated from symptomatic tissues and identified using molecular methods, confirming Koch's postulates. B. cinerea has already been reported from China on C. lyrate (Zhang 2006), a different species of C. hupingshanensis. To the best of our knowledge, this is the first report of B. cinerea causing gray mold on C. hupingshanensis in China and worldwide. Based on the widespread damage in the nursery, appropriate control strategies should be adopted. This study provides a basis for studying the epidemic and management of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1094/PDIS-04-21-0698-PDNDOI Listing
May 2021

Meta-analysis of randomized clinical trials comparing PCSK9 monoclonal antibody versus ezetimibe/placebo in patients at high cardiovascular risk.

Atherosclerosis 2021 06 7;326:25-34. Epub 2021 May 7.

Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan Province, PR China.

Background And Aims: Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) reduce circulating low-density lipoprotein cholesterol (LDL-C) by controlling the expression of LDL-receptor on the surface of hepatocytes. This meta-analysis aimed at evaluating the efficacy of PCSK9 mAbs on clinical and lipid-lowering outcomes.

Methods: PubMed, Embase, and ClinicalTrials.gov were searched from inception until November 2020 for randomized controlled trials (RCTs) that compared PCSK9 mAbs with ezetimibe or placebo in patients at high cardiovascular risk.

Results: Twenty eight RCTs with a total of 89,115 participants were included. Compared with placebo, PCSK9 mAbs significantly reduced the risk of major adverse cardiac events (MACEs) (RR 0.83, 95% CI 0.79 to 0.88, p < 0.00001). However, no difference was observed in occurring MACEs between PCSK9 mAbs and ezetimibe (RR 0.70, 95% CI 0.40 to 1.20, p = 0.20). Secondary analyses show that PCSK9 mAbs were not superior to ezetimibe in preventing stroke (RR 0.38, 95% CI 0.09 to 1.69, p = 0.20), myocardial infarction (RR 0.95, 95% CI 0.47 to 1.90, p = 0.88), and cardiovascular death (RR 0.44, 95% CI 0.14 to 1.43, p = 0.17). Compared with placebo, PCSK9 mAbs significantly reduced the incidence of stroke (RR 0.75, 95% CI 0.66 to 0.86, p < 0.0001) and myocardial infarction (RR 0.81, 95% CI 0.76 to 0.87, p < 0.00001), but not the risk of cardiovascular death (RR 0.96, 95% CI 0.86 to 1.07, p = 0.45). As for lipid-lowering efficacy, PCSK9 mAbs markedly reduced percent change of LDL-C from baseline to week 12 and 24 compared to ezetimibe or placebo.

Conclusions: In patients at high cardiovascular risk, PCSK9 mAbs could effectively reduce MACEs, stroke, and myocardial infarction compared with placebo. However, PCSK9 mAbs were not superior to ezetimibe in preventing adverse cardiovascular events in our study; RCTs with long-term follow-up and cardiovascular events as the research endpoint are still needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2021.04.008DOI Listing
June 2021

Adverse childhood experiences and risk of cancer during adulthood: A systematic review and meta-analysis.

Child Abuse Negl 2021 Jul 8;117:105088. Epub 2021 May 8.

Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, China. Electronic address:

Background: Research findings on the relationship between adverse childhood experiences (ACEs) and the risk of cancer were inconsistent.

Objective: The purpose of this study was to perform a quantitative synthesis of the preceding research findings.

Participants And Setting: System review and meta-analysis.

Methods: Electronic database of PubMed, Embase, Web of Science and Cochrane Library were systematically searched to identify relevant observational studies published not later than September 9, 2020. Specifically, original articles that reported the risk of cancer in adult populations that experienced ACEs before the age of 18 were selected. All pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using a random-effects model. Publication bias was examined using funnel plots, and sensitivity analysis was used to explore the stability of the pooled results.

Results: A total of 18 studies involving 406,210 participants were included in this review. Individuals with 2 or 3 kinds of ACEs (OR = 1.35, 95%CI:1.12,1.62) or at least 4 ACEs (OR = 2.17, 95%CI: 1.76,2.68) were at increased risk of cancer when compared with individuals with no ACEs. Of the different types of ACEs examined, physical abuse (OR = 1.23, 95%CI:1.05,1.43), sexual abuse (OR = 1.26, 95%CI:1.02,1.56), exposure to intimate partner violence (OR = 1.26, 95%CI:1.12,1.41) and financial difficulties in the family (OR = 1.16, 95%CI:1.00,1.33) were associated with the risk of any cancer.

Conclusions: These findings suggest that multiple ACEs may be a risk factor for cancer development. Therefore, prevention of ACEs and interventions for supporting those affected by ACEs are necessary.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chiabu.2021.105088DOI Listing
July 2021

Comparative study of hospitalized children with acute respiratory distress syndrome caused by SARS-CoV-2 and influenza virus.

BMC Infect Dis 2021 May 4;21(1):412. Epub 2021 May 4.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: Since the outbreak of coronavirus disease 2019 in December 2019, more than 8 million cases have occurred worldwide as of June 16, 2020. However, it is important to distinguish COVID-19 from other respiratory infectious diseases, such as influenza. Here, we comparatively described the clinical characteristics of children with COVID-19 and paediatric patients with influenza.

Methods: In this retrospective, single-centre study, we reviewed the electronic medical records of 585 paediatric patients with COVID-19 or influenza in Wuhan Children's Hospital, China. Clinical and epidemiological characteristics, laboratory findings, and clinical outcomes were comparatively analysed.

Results: The median ages were 6.96 years (IQR, 2-10.81) for children with confirmed COVID-19, 2.67 years (IQR, 1.03-15.25) for those with influenza A and 3.67 years (IQR, 1.62-5.54) for those with influenza B. Fever was a symptom in 84 (34.7%) COVID-19 cases, 132 (70.21%) influenza A cases and 111 (74.50%) influenza B cases. The median length of stay (LOS) was 11 (8-15) days for paediatric COVID-19 patients, 4 (3-6) days for influenza A patients and 5 (3-6) days for influenza B patients. Twenty-six (13.98%) influenza A patients and 18 (12.59%) influenza B patients presented with decreased white blood cell counts, while 13 (5.33%) COVID-19 patients presented with decreased white blood cell counts. Eight (3.28%) COVID-19 patients, 23 (12.71%) influenza A patients and 21 (14.79%) influenza B patients experienced lymphocytopenia. Acute cardiac injury occurred in 18 (7.29%) COVID-19 patients, while 37 (19.68%) influenza A and 27 (18.12%) influenza B patients had acute cardiac injury.

Conclusion: In this study, the illnesses of children with COVID-19 were demonstrated to be less severe than those of paediatric patients with influenza, and COVID-19 patients had milder illness and fewer complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-021-06068-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093914PMC
May 2021

The Direct Semi-Quantitative Detection of 18 Pathogens and Simultaneous Screening for Nine Resistance Genes in Clinical Urine Samples by a High-Throughput Multiplex Genetic Detection System.

Front Cell Infect Microbiol 2021 12;11:660461. Epub 2021 Apr 12.

Department of Laboratory Medicine, Huadong Hospital, Affiliated With Fudan University, Shanghai, China.

Background: Urinary tract infections (UTIs) are one the most common infections. The rapid and accurate identification of uropathogens, and the determination of antimicrobial susceptibility, are essential aspects of the management of UTIs. However, existing detection methods are associated with certain limitations. In this study, a new urinary tract infection high-throughput multiplex genetic detection system (UTI-HMGS) was developed for the semi-quantitative detection of 18 pathogens and the simultaneously screening of nine resistance genes directly from the clinical urine sample within 4 hours.

Methods: We designed and optimized a multiplex polymerase chain reaction (PCR) involving fluorescent dye-labeled specific primers to detect 18 pathogens and nine resistance genes. The specificity of the UTI-HMGS was tested using standard strains or plasmids for each gene target. The sensitivity of the UTI-HMGS assay was tested by the detection of serial tenfold dilutions of plasmids or simulated positive urine samples. We also collected clinical urine samples and used these to perform urine culture and antimicrobial susceptibility testing (AST). Finally, all urine samples were detected by UTI-HMGS and the results were compared with both urine culture and Sanger sequencing.

Results: UTI-HMGS showed high levels of sensitivity and specificity for the detection of uropathogens when compared with culture and sequencing. In addition, ten species of bacteria and three species of fungi were detected semi-quantitatively to allow accurate discrimination of significant bacteriuria and candiduria. The sensitivity of the UTI-HMGS for the all the target genes could reach 50 copies per reaction. In total, 531 urine samples were collected and analyzed by UTI-HMGS, which exhibited high levels of sensitivity and specificity for the detection of uropathogens and resistance genes when compared with Sanger sequencing. The results from UTI-HMGS showed that the detection rates of 15 pathogens were significantly higher (P<0.05) than that of the culture method. In addition, there were 41(7.72%, 41/531) urine samples were positive for difficult-to-culture pathogens, which were missed detected by routine culture method.

Conclusions: UTI-HMGS proved to be an efficient method for the direct semi-quantitative detection of 18 uropathogens and the simultaneously screening of nine antibiotic resistance genes in urine samples. The UTI-HMGS could represent an alternative method for the clinical detection and monitoring of antibiotic resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2021.660461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072482PMC
July 2021

Internal iliac artery balloon occlusion in the management of placenta accreta: A systematic review and meta-analysis.

Eur J Radiol 2021 Jun 20;139:109711. Epub 2021 Apr 20.

Department of Obstetrics and Gynecology, Chengdu Women and Children's Central Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu, 1617 Riyue Avenue, Qingyang District, Sichuan Province, China. Electronic address:

Purpose: To examine the effectiveness and safety of prophylactic internal iliac artery balloon occlusion for hemorrhage control in placenta accreta.

Method: EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials data-bases were searched through November 2020. Clinical trials comparing the management of placenta accreta with and without internal iliac artery balloon occlusion were included. The meta-analysis results were expressed as the risk ratio (RR) or mean difference, with 95 % CIs.

Results: Fifteen studies including 1098 women were eligible. No statistically significant difference was found between the internal arterial balloon occlusion group and the control group with respect to estimated blood loss volume (-0.525 mL, [95 % CI, -1.112 to -0.061], p = 0.079.), red blood cells (RBCs) transfused in observational studies (-0.682 mL, [95 % CI, -1.540 to 0.176], p = 0.119.) and in randomized controlled trials (0.134 mL, [95 % CI, -0.214 to 0.482], p = 0.451.), intensive care unit admission (p = 0.197), hysterectomy in observational studies (p = 0.969) and in randomized controlled trials (p = 0.323), urinary system injury in observational studies (p = 0.182) and in randomized controlled trials (p = 0.956), Apgar score at 5 min (p = 0.641), and neonatal intensive care unit admission (p = 0.973).

Conclusions: The currently available data demonstrate no significant differences between the internal iliac artery balloon occlusion group and the control group in blood loss and packed RBCs transfused for women with placenta accreta. Further large randomized controlled studies are needed to confirm our findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejrad.2021.109711DOI Listing
June 2021

Genomic population structure of Shanghai isolates and identification of genomic features uniquely linked with pathogenicity.

Virulence 2021 12;12(1):1258-1270

Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai, China.

Severe -linked gastric disorders are especially prevalent in the East Asia region. The ability of to cause different clinical outcomes is thought to be associated with unique sets of its genetic features. However, only few genetic features have been definitively linked to specific gastrointestinal pathologies. Genome heterogeneity of clinical strains from patients with four different gastric disorders was studied to explore the population structure and molecular genomic features and their association with pathogenicity. Population analysis showed that 92.9% of the Shanghai isolates were clustered in the East Asia group. Among 2,866 genes detected in all genomes, 1,146 genes formed the core genome, whereas 209 unique genes were detected in individual disease groups. The unique genes of peptic ulcer and gastric cancer groups represented the inorganic ion transport and metabolism function gene clusters. Sixteen virulence genes were detected with statistically different detection rates among the four disease groups. Furthermore, 127 clustered regularly interspaced short palindromic repeats were found with significantly different rates in the four disease groups. A total of 337 putative genomic islands were identified, and three genomic islands were individually found in more than 10% of strains. The genomic islands included several metabolism-associated genes and many genes with unknown function. In total, 88 sequence types were detected among the 112 Shanghai isolates. Our study provides an essential milestone in the mapping of specific genomic features and their functions to identify factors needed to induce specific gastric disorders in
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21505594.2021.1920762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081043PMC
December 2021

Characteristics of abnormal serum creatine kinase-MB levels in children with COVID-19.

World J Pediatr 2021 06 19;17(3):326-328. Epub 2021 Apr 19.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12519-020-00402-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054842PMC
June 2021

High Job Burnout Predicts Low Heart Rate Variability in the Working Population after a First Episode of Acute Coronary Syndrome.

Int J Environ Res Public Health 2021 03 26;18(7). Epub 2021 Mar 26.

Department of Environmental Health Sciences, Fielding School of Public Health, School of Nursing, University of California Los Angeles, Los Angeles, CA 90095, USA.

(1) Background: Job burnout may affect the prognosis of patients with acute coronary syndrome (ACS) through mechanisms involving heart rate variability (HRV). However, no study has yet examined those potential associations. Hence, we conducted the present study to investigate this issue. (2) Method: Participants included patients who presented with a first episode of ACS and who were employed. The Copenhagen Burnout Inventory (CBI) was used to assess job burnout. Twenty-four-hour ambulatory electrocardiography recorded HRV on four occasions, i.e., during the hospitalization and follow-ups at one, six, and 12 months, respectively. (3) Results: A total of 120 participants who at least completed three Holter examinations throughout the study were enrolled in the final analysis. Job burnout scores at baseline were inversely associated with LnSDNN, LnTP, LnHF, LnLF, LnULF, and LnVLF during the consequent one-year follow-up. Each 1 SD increase in job burnout scores predicted a decline ranging from 0.10 to 0.47 in the parameters described above (all < 0.05), and all relationships were independent of numerous confounders, including anxiety and depression. (4) Conclusion: High job burnout predicted reduced HRV parameters during the one-year period post-ACS in the working population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph18073431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037205PMC
March 2021

Raw biomass electroreforming coupled to green hydrogen generation.

Nat Commun 2021 03 31;12(1):2008. Epub 2021 Mar 31.

School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore, Singapore.

Despite the tremendous progress of coupling organic electrooxidation with hydrogen generation in a hybrid electrolysis, electroreforming of raw biomass coupled to green hydrogen generation has not been reported yet due to the rigid polymeric structures of raw biomass. Herein, we electrooxidize the most abundant natural amino biopolymer chitin to acetate with over 90% yield in hybrid electrolysis. The overall energy consumption of electrolysis can be reduced by 15% due to the thermodynamically and kinetically more favorable chitin oxidation over water oxidation. In obvious contrast to small organics as the anodic reactant, the abundance of chitin endows the new oxidation reaction excellent scalability. A solar-driven electroreforming of chitin and chitin-containing shrimp shell waste is coupled to safe green hydrogen production thanks to the liquid anodic product and suppression of oxygen evolution. Our work thus demonstrates a scalable and safe process for resource upcycling and green hydrogen production for a sustainable energy future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-22250-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012647PMC
March 2021

A drug targeting 5-lipoxygenase enhances the activity of a JAK2 inhibitor in CD34 bone marrow cells from patients with JAK2V617F-positive polycythemia vera .

Oncol Lett 2021 May 4;21(5):351. Epub 2021 Mar 4.

Department of Hematology, The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, Hunan 412000, P.R. China.

Janus kinase 2 (JAK2) inhibitors, the first targeted treatments for myeloproliferative neoplasms (MPNs), provide substantial benefits, including a marked reduction in splenomegaly and MPN-associated symptoms. However, these drugs rarely induce molecular remission in patients with MPNs. Zileuton, a 5-lipoxygenase (5-LO) inhibitor, has been demonstrated to selectively deplete hematopoietic stem cells (HSCs) expressing a JAK2 point mutation (JAK2V617F) in mouse models of JAK2V617F-induced polycythemia vera (PV). To determine the potential activity of 5-LO inhibitors in combination with JAK inhibitors against human PV HSCs, the present study first analyzed 5-LO expression in CD34 bone marrow cells from patients with JAK2V617F-positive PV using western blotting and reverse transcription-quantitative PCR, and then examined the effect of zileuton combined with ruxolitinib on colony formation using a colony formation assay. Furthermore, cell cycle and apoptosis in CD34 cells from patients with PV and healthy volunteers were determined by flow cytometry. In the present study, 5-LO expression was upregulated in CD34 cells from patients with PV compared with in CD34 cells from healthy volunteers. Higher levels of leukotriene B4, a product of the 5-LO signaling pathway, were detected in patients with PV compared with in healthy volunteers. Zileuton treatment suppressed the colony formation of CD34 cells from patients with PV in a dose-dependent manner. Furthermore, zileuton and ruxolitinib exerted their anticancer effects by suppressing hematopoietic colony formation, inducing apoptosis and arresting the cell cycle of human CD34 cells from patients with PV. The combination of these two drugs exerted a more beneficial effect than either agent alone. Based on these data, zileuton enhanced the antitumor activity of low-dose ruxolitinib in hematopoietic progenitor cells from patients with PV, providing conceptual validation for further clinical applications of combination treatment with ruxolitinib and zileuton for patients with PV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2021.12612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967924PMC
May 2021

Overexpressed NEDD8 as a potential therapeutic target in esophageal squamous cell carcinoma.

Cancer Biol Med 2021 Mar 18. Epub 2021 Mar 18.

Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.

Objective: The hyperactivated neddylation pathway plays an important role in tumorigenesis and is emerging as a promising anticancer target. We aimed to study whether NEDD8 (neural precursor cell expressed, developmentally down-regulated 8) might serve as a therapeutic target in esophageal squamous cell carcinoma (ESCC).

Methods: The clinical relevance of NEDD8 expression was evaluated by using The Cancer Genome Atlas (TCGA) database and tissue arrays. NEDD8-knockdown ESCC cells generated with the CRISPR/Cas9 system were used to explore the anticancer effects and mechanisms. Quantitative proteomic analysis was used to examine the variations in NEDD8 knockdown-induced biological pathways. The cell cycle and apoptosis were assessed with fluorescence activated cell sorting. A subcutaneous-transplantation mouse tumor model was established to investigate the anticancer potential of NEDD8 silencing .

Results: NEDD8 was upregulated at both the mRNA and protein expression levels in ESCC, and NEDD8 overexpression was associated with poorer overall patient survival (mRNA level: = 0.028, protein level: = 0.026, log-rank test). Downregulation of NEDD8 significantly suppressed tumor growth both and . Quantitative proteomic analysis revealed that downregulation of NEDD8 induced cell cycle arrest, DNA damage, and apoptosis in ESCC cells. Mechanistic studies demonstrated that NEDD8 knockdown led to the accumulation of cullin-RING E3 ubiquitin ligases (CRLs) substrates through inactivation of CRLs, thus suppressing the malignant phenotype by inducing cell cycle arrest and apoptosis in ESCC. Rescue experiments demonstrated that the induction of apoptosis after NEDD8 silencing was attenuated by DR5 knockdown.

Conclusions: Our study elucidated the anti-ESCC effects and underlying mechanisms of NEDD8 knockdown, and validated NEDD8 as a potential target for ESCC therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0484DOI Listing
March 2021

DeepS: A web server for image optical sectioning and super resolution microscopy based on a deep learning framework.

Bioinformatics 2021 Mar 2. Epub 2021 Mar 2.

Chinese Institute for Brain Research, Beijing (CIBR), 102206, CN.

Motivation: Microscopy technology plays important roles in many biological research fields. Solvent-cleared brain high-resolution (HR) 3 D image reconstruction is an important microscopy application. However, 3 D microscopy image generation is time-consuming and expensive. Therefore, we have developed a deep learning framework (DeepS) for both image optical sectioning and super resolution microscopy.

Results: Using DeepS to perform super resolution solvent-cleared mouse brain microscopy 3 D image yields improved performance in comparison with the standard image processing workflow. We have also developed a web server to allow online usage of DeepS. Users can train their own models with only one pair of training images using the transfer learning function of the web server.

Availability: http://deeps.cibr.ac.cn.

Supplementary Information: Supplementary data are available at Bioinformatics online.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/btab144DOI Listing
March 2021
-->