Publications by authors named "Yu Qin"

672 Publications

An ABCC-type transporter endowing glyphosate resistance in plants.

Proc Natl Acad Sci U S A 2021 Apr;118(16)

Australian Herbicide Resistance Initiative, School of Agriculture and Environment, University of Western Australia, WA 6009, Australia;

Glyphosate is the most widely used herbicide in world agriculture and for general vegetation control in a wide range of situations. Global and often intensive glyphosate selection of very large weedy plant populations has resulted in widespread glyphosate resistance evolution in populations of many weed species. Here, working with a glyphosate-resistant (GR) population that evolved in a Western Australia agricultural field, we identified an ATP-binding cassette (ABC) transporter () that is consistently up-regulated in GR plants. When expressed in transgenic rice, this transporter endowed glyphosate resistance. Equally, rice, maize, and soybean overexpressing the ortholog genes were made resistant to glyphosate. Conversely, CRISPR/Cas9-mediated knockout of the ortholog gene increased rice susceptibility to glyphosate. Subcellular localization analysis and quantification of glyphosate cellular levels in treated transgenic rice plants and isolated leaf protoplasts as well as structural modeling support that EcABCC8 is likely a plasma membrane-localized transporter extruding cytoplasmic glyphosate to the apoplast, lowering the cellular glyphosate level. This is a report of a membrane transporter effluxing glyphosate in a GR plant species, and its function is likely conserved in crop plant species.
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http://dx.doi.org/10.1073/pnas.2100136118DOI Listing
April 2021

Dinitroaniline Herbicide Resistance and Mechanisms in Weeds.

Front Plant Sci 2021 25;12:634018. Epub 2021 Mar 25.

Australian Herbicide Resistance Initiative (AHRI), School of Agriculture and Environment, University of Western Australia (UWA), Perth, WA, Australia.

Dinitroanilines are microtubule inhibitors, targeting tubulin proteins in plants and protists. Dinitroaniline herbicides, such as trifluralin, pendimethalin and oryzalin, have been used as pre-emergence herbicides for weed control for decades. With widespread resistance to post-emergence herbicides in weeds, the use of pre-emergence herbicides such as dinitroanilines has increased, in part, due to relatively slow evolution of resistance in weeds to these herbicides. Target-site resistance (TSR) to dinitroaniline herbicides due to point mutations in α-tubulin genes has been confirmed in a few weedy plant species (e.g., , , and recently in ). Of particular interest is the resistance mutation Arg-243-Met identified from dinitroaniline-resistant that causes helical growth when plants are homozygous for the mutation. The recessive nature of the TSR, plus possible fitness cost for some resistance mutations, likely slows resistance evolution. Furthermore, non-target-site resistance (NTSR) to dinitroanilines has been rarely reported and only confirmed in due to enhanced herbicide metabolism (metabolic resistance). A cytochrome P450 gene (CYP81A10) has been recently identified in that confers resistance to trifluralin. Moreover, TSR and NTSR have been shown to co-exist in the same weedy species, population, and plant. The implication of knowledge and information on TSR and NTSR in management of dinitroaniline resistance is discussed.
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http://dx.doi.org/10.3389/fpls.2021.634018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027333PMC
March 2021

Viologen-Based Cationic Metal-Organic Framework for Efficient CrO Adsorption and Dye Separation.

Inorg Chem 2021 Apr 7. Epub 2021 Apr 7.

School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116, P. R. China.

A novel cationic metal-organic framework composed of {Cu(COO)} paddle-wheel units and a tetracarboxylic viologen derivative, namely, {[Cu(bdcbp)(HO)]·2NO·2HO} (, HbdcbpCl = 1,1'-bis(3,5-dicarboxyphenyl)-4,4'-bipyridinium dichloride), has been successfully synthesized and structurally characterized. In , the {Cu(COO)} unit and viologen derivative both act as four-connected nodes forming an ssb-type cationic network with 4.8 topology, in which the positive charges are distributed on the organic viologen moieties. Deeper insight of the structure indicates that the 3D architecture of can be seen as packing of a 26-faceted polyhedral cage and two cuboid cages. Notably, displays a highly efficient anion exchange ability for capture and removal of anionic pollutants. UV-vis absorption spectra and digital images demonstrate that is capable of adsorbing the dichromate anion and anionic dyes effectively, such as methyl orange (MO), Congo red (CR), and New Coccine (NC). Meaningfully, anionic dyes (MO, CR, and NC) can be efficiently and selectively removed by in the presence of cationic dye methylene blue (MLB). Such behaviors of anionic pollutant adsorption and dye separation are mainly caused by an ion-exchange process facilitated by the large cavity and decentralized distribution of positive charge in .
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http://dx.doi.org/10.1021/acs.inorgchem.1c00404DOI Listing
April 2021

The effect of coronary slow flow on left atrial structure and function.

Sci Rep 2021 Apr 5;11(1):7511. Epub 2021 Apr 5.

Department of Cardiology, Affiliated Zhongshan Hospital of Dalian University, Dalian, 620061, Liaoning Province, China.

The coronary slow flow phenomenon (CSFP) is common in coronary angiography, however its impact on left atrial (LA) function is still controversial. This study aims to evaluate the LA structure and function of patients with CSFP using two-dimensional speckle tracking echocardiography (2D-STE). Consecutive patients scheduled for coronary angiography from January 2016 to September 2017 were enrolled in this study. Patients' demographic data, clinical histories, laboratory and angiographic findings were collected and recorded. Diagnostic criteria for CSFP is based on Beltrame et al. proposed in 2012. Meanwhile 139 patients who have no significant stenosis (≤ 40%) and normal blood flow were selected as control. All patients received an echocardiographic examination 24 h before coronary angiography. LA structure and function were measured with echocardiography and 2D-STE. Our results showed that among the 1,954 patients who had received coronary angiography, 512 patients were included in the analysis after the exclusion criteria was implemented. Of those, 101 patients met the CSFP criteria (5.5%). CSFP is mainly seen in LAD (~ 70%). There was no statistical difference in baseline characteristics between the CSFP group and control group, except for a higher proportion of smokers in the CSFP group (P = 0.001). The percentage of monocytes is an independent risk factor for the occurrence of CSFP (P = 0.036) after binary logistic regression analysis. The LA global longitudinal strain (LA-GLS, represents reservoir functions) decreased and LA strain rate at late diastole (LA-SRa, represents booster function) increased in patients with CSFP compared to the control group (P < 0.05). Correlation test of continuous variables by Pearson test suggested that LA-GLS was negatively correlated with TIMI frame count (TFC). We concluded that the percentage of monocytes is an independent risk factor for the CSFP; the LA reservoir and booster functions were impaired in patients with CSFP; LA-GLS is negatively correlated with TFC.
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http://dx.doi.org/10.1038/s41598-021-87193-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021584PMC
April 2021

Overexpression of AGAMOUS-like gene PfAG5 promotes early flowering in Polypogon fugax.

Funct Plant Biol 2021 Apr 6. Epub 2021 Apr 6.

Herbicides are the major tool for controlling large populations of yield depleting weeds. However, over-reliance on herbicides has resulted in weed adaptation and herbicide resistance. In recent years, early flowering weed species related to herbicide resistance is emerging, which may cause seed loss before crop harvest, creating a new problem for non-chemical weed management. In this study, a homologue gene of AGAMOUS sub-family (referred to as PfAG5) of the MADS-box family was cloned from plants of an early flowering Polypogon fugax Nees ex Steud. population resistant to the ACCase inhibitor herbicide (clodinafop-propargyl). The PfAG5 gene was functionally characterised in Arabidopsis thaliana L. Overexpression of the PfAG5 gene in Arabidopsis resulted in early flowering, abnormal flowers (e.g. small petals), short plants and reduced seed set, compared with the wild type. The expression of the PfAG5 gene was high in leaves and flowers, but low in pods in transgenic Arabidopsis. The PfAG5 gene was expressed earlier and higher in the resistant (R) than the susceptible (S) P. fugax plants. Furthermore, one protein (FRIGIDA-like) with relevance to flowering time regulation and interacts with PfAG5 in resistant (R) P. fugax was identified by the yeast two-hybrid and pull-down assays. These results suggest that the PfAG5 gene is involved in modulating early flowering in P. fugax.
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http://dx.doi.org/10.1071/FP21047DOI Listing
April 2021

Harnessing Big Data to Optimize an Algorithm for Rapid Diagnosis of Pulmonary Tuberculosis in a Real-World Setting.

Front Cell Infect Microbiol 2021 18;11:650163. Epub 2021 Mar 18.

Department of Pediatrics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.

Background: The prompt diagnosis of pulmonary tuberculosis (PTB) remains a challenge in clinical practice. The present study aimed to optimize an algorithm for rapid diagnosis of PTB in a real-world setting.

Methods: 28,171 adult inpatients suspected of having PTB in China were retrospectively analyzed. Bronchoalveolar lavage fluid (BALF) and/or sputum were used for acid-fast bacilli (AFB) smear, Xpert MTB/RIF (Xpert), and culture. A positive mycobacterial culture was used as the reference standard. Peripheral blood mononuclear cells (PBMC) were used for T-SPOT.. We analyzed specimen types' effect on these assays' performance, determined the number of smears for diagnosing PTB, and evaluated the ability of these assays performed alone, or in combination, to diagnose PTB and nontuberculous mycobacteria (NTM) infections.

Results: Sputum and BALF showed moderate to substantial consistency when they were used for AFB smear or Xpert, with a higher positive detection rate by BALF. 3-4 smears had a higher sensitivity than 1-2 smears. Moreover, simultaneous combination of AFB and Xpert correctly identified 44/51 of AFB/Xpert and 6/7 of AFB/Xpert cases as PTB and NTM, respectively. Lastly, when combined with AFB/Xpert sequentially, T-SPOT showed limited roles in patients that were either AFB or Xpert. However, T-SPOT (manufacturer-defined cut-off) showed a high negative predicative value (99.1%) and suboptimal sensitivity (74.4%), and TBAg/PHA (ratio of -specific antigens to phytohaemagglutinin spot-forming cells, which is a modified method calculating T-SPOT. assay results) ≥0.3 demonstrated a high specificity (95.7%) and a relatively low sensitivity (16.3%) in AFB/Xpert patients.

Conclusions: Concurrently performing AFB smear (at least 3 smears) and Xpert on sputum and/or BALF could aid in rapid diagnosis of PTB and NTM infections in a real-world high-burden setting. If available, BALF is preferred for both AFB smear and Xpert. Expanding this algorithm, PBMC T-SPOT and TBAg/PHA ratios have a supplementary role for PTB diagnosis in AFB/Xpert patients (moderately ruling out PTB and ruling in PTB, respectively). Our findings may also inform policy makers' decisions regarding prevention and control of TB in a high burden setting.
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http://dx.doi.org/10.3389/fcimb.2021.650163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012509PMC
March 2021

Molecular epidemiology analysis of early variants of SARS-CoV-2 reveals the potential impact of mutations P504L and Y541C (NSP13) in the clinical COVID-19 outcomes.

Infect Genet Evol 2021 Mar 30:104831. Epub 2021 Mar 30.

Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Gynecologic Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused global pandemic with alarming speed, comprehensively analyzing the mutation and evolution of early SARS-CoV-2 strains contributes to detect and prevent such virus. Here, we explored 1962 high-quality genomes of early SARS-CoV-2 strains obtained from 42 countries before April 2020. The changing trends of genetic variations in SARS-CoV-2 strains over time and country were subsequently identified. In addition, viral genotype mapping and phylogenetic analysis were performed to identify the variation features of SARS-CoV-2. Results showed that 57.89% of genetic variations involved in ORF1ab, most of which (68.85%) were nonsynonymous. Haplotype maps and phylogenetic tree analysis showed that amino acid variations in ORF1ab (p.5828P > L and p.5865Y > C, also NSP13: P504L and NSP13: Y541C) were the important characteristics of such clade. Furthermore, these variants showed more significant aggregation in the United States (P = 2.92E-66, 95%) than in Australia or Canada, especially in strains from Washington State (P = 1.56E-23, 77.65%). Further analysis demonstrated that the report date of the variants was associated with the date of increased infections and the date of recovery and fatality rate change in the United States. More importantly, the fatality rate in Washington State was higher (4.13%) and showed poorer outcomes (P = 4.12E-21 in fatality rate, P = 3.64E-29 in death and recovered cases) than found in other states containing a small proportion of strains with such variants. Using sequence alignment, we found that variations at the 504 and 541 sites had functional effects on NSP13. In this study, we comprehensively analyzed genetic variations in SARS-CoV-2, gaining insights into amino acid variations in ORF1ab and COVID-19 outcomes.
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http://dx.doi.org/10.1016/j.meegid.2021.104831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010360PMC
March 2021

Selective autophagy of AKAP11 activates cAMP/PKA to fuel mitochondrial metabolism and tumor cell growth.

Proc Natl Acad Sci U S A 2021 Apr;118(14)

Department of Neurology, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029;

Autophagy is a catabolic pathway that provides self-nourishment and maintenance of cellular homeostasis. Autophagy is a fundamental cell protection pathway through metabolic recycling of various intracellular cargos and supplying the breakdown products. Here, we report an autophagy function in governing cell protection during cellular response to energy crisis through cell metabolic rewiring. We observe a role of selective type of autophagy in direct activation of cyclic AMP protein kinase A (PKA) and rejuvenation of mitochondrial function. Mechanistically, autophagy selectively degrades the inhibitory subunit RI of PKA holoenzyme through A-kinase-anchoring protein (AKAP) 11. AKAP11 acts as an autophagy receptor that recruits RI to autophagosomes via LC3. Glucose starvation induces AKAP11-dependent degradation of RI, resulting in PKA activation that potentiates PKA-cAMP response element-binding signaling, mitochondria respiration, and ATP production in accordance with mitochondrial elongation. AKAP11 deficiency inhibits PKA activation and impairs cell survival upon glucose starvation. Our results thus expand the view of autophagy cytoprotection mechanism by demonstrating selective autophagy in RI degradation and PKA activation that fuels the mitochondrial metabolism and confers cell resistance to glucose deprivation implicated in tumor growth.
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http://dx.doi.org/10.1073/pnas.2020215118DOI Listing
April 2021

Effectiveness of cognitive behavior therapy for sleep disturbance and glycemic control in persons with type 2 diabetes mellitus: A community-based randomized controlled trial in China.

World J Diabetes 2021 Mar;12(3):292-305

Department of Control and Prevention of Chronic Non-communicable Diseases, Xuzhou Center for Disease Control and Prevention, Xuzhou 221006, Jiangsu Province, China.

Background: Poor sleep quality is a common clinical feature in patients with type 2 diabetes mellitus (T2DM), and often negatively related with glycemic control. Cognitive behavioral therapy (CBT) may improve sleep quality and reduce blood sugar levels in patients with T2DM. However, it is not entirely clear whether CBT delivered by general practitioners is effective for poor sleep quality in T2DM patients in community settings.

Aim: To test the effect of CBT delivered by general practitioners in improving sleep quality and reducing glycemic levels in patients with T2DM in community.

Methods: A cluster randomized controlled trial was conducted from September 2018 to October 2019 in communities of China. Overall 1033 persons with T2DM and poor sleep quality received CBT plus usual care or usual care. Glycosylated hemoglobin A1c (HbAlc) and sleep quality [Pittsburgh Sleep Quality Index (PSQI)] were assessed. Repeated measures analysis of variance and generalized linear mixed effects models were used to estimate the intervention effects on hemoglobin A1c and sleep quality.

Results: The CBT group had 0.64, 0.50, and 0.9 lower PSQI scores than the control group at 2 mo, 6 mo, and 12 mo, respectively. The CBT group showed 0.17 and 0.43 lower HbAlc values than the control group at 6 mo and 12 mo. The intervention on mean ΔHbAlc values was significant at 12 mo ( = 3.68, < 0.01) and that mean ΔPSQI scores were closely related to ΔHbAlc values ( = 7.02, < 0.01). Intention-to-treat analysis for primary and secondary outcomes showed identical results with completed samples. No adverse events were reported.

Conclusion: CBT delivered by general practitioners, as an effective and practical method, could reduce glycemic levels and improve sleep quality for patients with T2DM in community.
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http://dx.doi.org/10.4239/wjd.v12.i3.292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958479PMC
March 2021

CDK1 serves as a novel therapeutic target for endometrioid endometrial cancer.

J Cancer 2021 22;12(8):2206-2215. Epub 2021 Feb 22.

Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China, 310006.

Endometrial cancer (EC) is one of the most common and prevalent gynecologic malignancies worldwide. The aim of this study was to identify a novel therapeutic target for endometrioid endometrial cancer. Bioinformatic analysis was performed and CDK1 was screen out as one of the hub genes in the pathogenesis of EC. Immunohistochemistry was used to verify the expression of CDK1 in endometrial cancer tissue. Cell viability and colony formation were used to study the effects of CDK1 on the proliferation and colony formation of endometrial cancer cells . Apoptosis and cell cycle assays were used to elucidate the mechanism of CDK1 affecting cell proliferation. Tumor xenograft transplantation assay was performed to show the effects of CDK1 on the growth of endometrial cancer cells . CDK1 was over expressed in endometrioid endometrial cancer, and accumulation of cytoplasmic CDK1 was associated with histological grade of EC. CDK1 promoted endometrial cancer cell growth and colony formation . The inhibition of CDK1 activity induced cell apoptosis and caused G2/M phase arrest of cell cycle in endometrial cancer cells. The inhibition of CDK1 activity also inhibited endometrial cancer growth in xenograft models. CDK1 was involved in the pathogenesis of endometrioid endometrial cancer and provided a novel therapeutic target for endometrioid endometrial cancer.
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http://dx.doi.org/10.7150/jca.51139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974891PMC
February 2021

The association between daily total physical activity and risk of cardiovascular disease among hypertensive patients: a 10-year prospective cohort study in China.

BMC Public Health 2021 Mar 16;21(1):517. Epub 2021 Mar 16.

Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.

Background: The effect of high levels of physical activity and relationship between daily total physical activity and the risk of cardiovascular disease (CVD) among hypertensive people were not clear. This study aimed to explore the optimum level of physical activity for CVD prevention.

Methods: Data used in the present study was derived from the sub-study of China Kadoorie Biobank study (CKB) in Jiangsu province of China. The CKB was a prospective cohort study established during 2004-2008. At baseline, 53,259 participants aged 35-74 years were recruited for the CKB Jiangsu sub-study conducted in Wuzhong district of Suzhou City. Among those 53,259 participants, the 20,179 hypertensive individuals were our study population. The outcome events were cardiovascular diseases (CVDs), while the independent variable was total daily physical activity. The Cox proportional hazard models were introduced to investigate the association between total physical activity and CVDs, reporting as hazard ratios (HR) and 95% confidence intervals (CIs).

Results: During a 10.1-year follow-up, 2419 CVD cases were identified. After adjustment for potential confounding factors, compared with participants at the lowest level of daily total physical activity, the hazard ratios for CVDs were 0.87 (95%CI: 0.79-0.97), 0.73 (95%CI: 0.65-0.83) and 0.75 (95%CI: 0.65-0.85) for participants within 2, 3 and 4 quartiles of physical activity. Such a negative association between total physical activity and CVDs were also observed among participants by gender and age-group, but within patients with stage 1 hypertension only. Moreover, the association of physical activity with CVDs was U-shape and the lowest HR (0.63, 95%CI: 0.54-0.74) was observed at 35.4 MET-h/d of total physical activity.

Conclusions: Total daily physical activity was negatively associated with CVDs among hypertensive adults in China, and this association was U-shape. It has some public health implications that community-based total physical activity intervention campaigns can be of help for CVDs prevention among hypertensive people in China.
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http://dx.doi.org/10.1186/s12889-021-10551-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968198PMC
March 2021

Anthraquinone derivative C10 inhibits proliferation and cell cycle progression in colon cancer cells via the Jak2/Stat3 signaling pathway.

Toxicol Appl Pharmacol 2021 May 13;418:115481. Epub 2021 Mar 13.

Key Laboratory of Chemical Biology and Molecular Engineering of the Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, China.

Since its discovery, anthraquinone has become very valuable as a lead compound in the development of anti-cancer drugs. Previously, we designed and synthesized a new type of amide anthraquinone derivative (1-nitro-2-acylanthraquinone glycine, C10) with good activity against colon cancer. However, its effect and the underlying mechanism are unclear. In this study, C10 significantly inhibited the proliferation of HCT116 and HT29 colon cancer cells by blocking the cell cycle at the G2/M phase. C10 also plays a role in cell cycle arrest by reducing the protein and gene expression levels of cyclin B1 and its downstream signaling molecule cyclin-dependent kinase (CDK1). In addition, molecular docking studies showed that C10 has high affinity for Jak2, the first target in the cell cycle-related Jak2/Stat3 signaling pathway. Furthermore, C10 downregulated the expression of Jak2/Stat3 signaling pathway-related signaling molecules proteins and genes, and up-regulated the expression of PIAS-3, the upstream signaling molecule of Stat3, thereby down-regulating Stat3 phosphorylation. C10 reversed the expression of Jak2/Stat3 signaling pathway-related molecules activated by IL-6. Overall, our results indicate for the first time that C10 induces cell cycle arrest and inhibits cell proliferation by inhibiting the Jak2/Stat3 signaling pathway. This study provides new insights into the potential role of Jak2/Stat3 in the regulating cell cycle-related signaling pathways that mediate the inhibitory effects of C10 on colon cancer cell proliferation.
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http://dx.doi.org/10.1016/j.taap.2021.115481DOI Listing
May 2021

Ethylene-regulated asymmetric growth of the petal base promotes flower opening in rose (Rosa hybrida).

Plant Cell 2021 Feb 2. Epub 2021 Feb 2.

Department of Ornamental Horticulture, State Key Laboratory of Agrobiotechnology, Beijing Key Laboratory of Development and Quality Control of Ornamental Crops, China Agricultural University, Beijing 100193, China.

Flowers are the core reproductive structures and key distinguishing features of angiosperms. Flower opening to expose stamens and gynoecia is important in cases where pollinators much be attracted to promote cross-pollination, which can enhance reproductive success and species preservation. The floral opening process is accompanied by the coordinated movement of various floral organs, particularly petals. However, the mechanisms underlying petal movement and flower opening are not well understood. Here, we integrated anatomical, physiological, and molecular approaches to determine the petal movement regulatory network using rose (Rosa hybrida) as a model. We found that PETAL MOVEMENT-RELATED PROTEIN1 (RhPMP1), a homeodomain transcription factor (TF) gene, is a direct target of ETHYLENE INSENSITIVE3, a TF that functions downstream of ethylene signaling. RhPMP1 expression was upregulated by ethylene and specifically activated endoreduplication of parenchyma cells on the adaxial side of the petal (ADSP) base by inducing the expression of RhAPC3b, a gene encoding the core subunit of the Anaphase-Promoting Complex. Cell expansion of the parenchyma on the ADSP base was subsequently enhanced, thus resulting in asymmetric growth of the petal base, leading to the typical epinastic movement of petals and flower opening. These findings provide insights into the pathway regulating petal movement and associated flower-opening mechanisms.
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http://dx.doi.org/10.1093/plcell/koab031DOI Listing
February 2021

Identification of a Potentially Functional microRNA-mRNA Regulatory Network in Lung Adenocarcinoma Using a Bioinformatics Analysis.

Front Cell Dev Biol 2021 18;9:641840. Epub 2021 Feb 18.

The First School of Clinical Medicine, Lanzhou University, Lanzhou, China.

Background: Lung adenocarcinoma (LUAD) is a common lung cancer with a high mortality, for which microRNAs (miRNAs) play a vital role in its regulation. Multiple messenger RNAs (mRNAs) may be regulated by miRNAs, involved in LUAD tumorigenesis and progression. However, the miRNA-mRNA regulatory network involved in LUAD has not been fully elucidated.

Methods: Differentially expressed miRNAs and mRNA were derived from the Cancer Genome Atlas (TCGA) dataset in tissue samples and from our microarray data in plasma (GSE151963). Then, common differentially expressed (Co-DE) miRNAs were obtained through intersected analyses between the above two datasets. An overlap was applied to confirm the Co-DEmRNAs identified both in targeted mRNAs and DEmRNAs in TCGA. A miRNA-mRNA regulatory network was constructed using Cytoscape. The top five miRNA were identified as hub miRNA by degrees in the network. The functions and signaling pathways associated with the hub miRNA-targeted genes were revealed through Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The key mRNAs in the protein-protein interaction (PPI) network were identified using the STRING database and CytoHubba. Survival analyses were performed using Gene Expression Profiling Interactive Analysis (GEPIA).

Results: The miRNA-mRNA regulatory network consists of 19 Co-DEmiRNAs and 760 Co-DEmRNAs. The five miRNAs (miR-539-5p, miR-656-3p, miR-2110, let-7b-5p, and miR-92b-3p) in the network were identified as hub miRNAs by degrees (>100). The 677 Co-DEmRNAs were targeted mRNAs from the five hub miRNAs, showing the roles in the functional analyses of the GO analysis and KEGG pathways (inclusion criteria: 836 and 48, respectively). The PPI network and Cytoscape analyses revealed that the top ten key mRNAs were NOTCH1, MMP2, IGF1, KDR, SPP1, FLT1, HGF, TEK, ANGPT1, and PDGFB. SPP1 and HGF emerged as hub genes through survival analysis. A high SPP1 expression indicated a poor survival, whereas HGF positively associated with survival outcomes in LUAD.

Conclusion: This study investigated a miRNA-mRNA regulatory network associated with LUAD, exploring the hub miRNAs and potential functions of mRNA in the network. These findings contribute to identify new prognostic markers and therapeutic targets for LUAD patients in clinical settings.
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http://dx.doi.org/10.3389/fcell.2021.641840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930498PMC
February 2021

Reporting and methodological quality of COVID-19 systematic reviews needs to be improved: an evidence mapping.

J Clin Epidemiol 2021 Feb 28;135:17-28. Epub 2021 Feb 28.

Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China; Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, China; WHO Collaborating Centre for Guideline Implementation and Knowledge Translation, Lanzhou University, Lanzhou, China; Evidence Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China. Electronic address:

Objectives: To assess the reporting and methodological quality of COVID-19 systematic reviews, and to analyze trends and gaps in the quality, clinical topics, author countries, and populations of the reviews using an evidence mapping approach.

Study Design And Setting: A structured search for systematic reviews concerning COVID-19 was performed using PubMed, Embase, Cochrane Library, Campbell Library, Web of Science, CBM, WanFang Data, CNKI, and CQVIP from inception until June 2020. The quality of each review was assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) checklist and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist.

Results: In total, 243 systematic reviews met the inclusion criteria, over 50% of which (128, 52.7%) were from 14 developing countries, with China contributing the most reviews (76, 31.3%). In terms of methodological quality of the studies, 30 (12.3%) were of moderate quality, 63 (25.9%) were of low quality, and 150 (61.7%) were of critically low quality. In terms of reporting quality, the median (interquartile range) PRISMA score was 14 (10-18). Regarding the topics of the reviews, 24 (9.9%) focused on the prevalence of COVID-19, 69 (28.4%) focused on the clinical manifestations, 30 (12.3%) focused on etiology, 43 (17.7%) focused on diagnosis, 65 (26.7%) focused on treatment, 104 (42.8%) focused on prognosis, and 25 (10.3%) focused on prevention. These studies mainly focused on general patients with COVID-19 (161, 66.3%), followed by children (22, 9.1%) and pregnant patients (18, 7.4%).

Conclusion: This study systematically evaluated the methodological and reporting quality of systematic reviews of COVID-19, summarizing and analyzing trends in their clinical topics, author countries, and study populations.
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http://dx.doi.org/10.1016/j.jclinepi.2021.02.021DOI Listing
February 2021

pH-sensitive and bubble-generating mesoporous silica-based nanoparticles for enhanced tumor combination therapy.

Acta Pharm Sin B 2021 Feb 2;11(2):520-533. Epub 2020 Sep 2.

Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China.

Chemotherapy has been a major option in clinic treatment of malignant tumors. However, single chemotherapy faces some drawbacks, such as multidrug resistance, severe side effects, which hinder its clinic application in tumor treatment. Multifunctional nanoparticles loading with chemotherapeutic agent and photosensitizer could be a promising way to efficiently conduct tumor combination therapy. In the current study, a novel pH-sensitive and bubble-generating mesoporous silica-based drug delivery system (denoted as M(a)D@PI-PEG-RGD) was constructed. Ammonium bicarbonate (NHHCO; abc) and chemotherapeutic agent doxorubicin (DOX) were loaded into the pores of mesoporous silica. Indocyanine green (ICG) as a photothermal and photodynamic agent was loaded onto the polydopamine (PDA) layer surface. The synthesized nanoparticles displayed a narrow polydispersity (PDI) and small particle size as characterized through dynamic light scattering-autosizer analysis. The nanoparticles also showed high targeting efficacy through RGD modification as indicated by cellular uptake and animal studies. DOX release analysis confirmed that the nanoparticles were pH-dependent and that NHHCO accelerated drug release. At the same time, the nanoparticles had obvious photothermal and photodynamic effects performed by ICG which restrained tumor growth remarkably. In summary, the multifunctional nanoparticles presented a promising system for combination therapy.
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http://dx.doi.org/10.1016/j.apsb.2020.08.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893139PMC
February 2021

Free CA125 promotes ovarian cancer cell migration and tumor metastasis by binding Mesothelin to reduce DKK1 expression and activate the SGK3/FOXO3 pathway.

Int J Biol Sci 2021 14;17(2):574-588. Epub 2021 Jan 14.

Integrative Medical Diagnosis Laboratory, Tianjin Nankai Hospital, Tianjin, 300100, China; School of Medical Technology, Tianjin Medical University, Tianjin 300203, China.

CA125/MUC16 is an O-glycosylated protein that is expressed on the surfaces of ovarian epithelial cells. This molecule is a widely used tumor-associated marker for diagnosis of ovarian cancer. Recently, CA125 was shown to be involved in ovarian cancer metastasis. The purpose of this study was to investigate the mechanism of CA125 during ovarian cancer metastasis. We analyzed the Oncomine and CSIOVDB databases to determine the expression levels of DKK1 in ovarian cancer. DKK1 expression levels were upregulated or downregulated and applied with CA125 to Transwell and Western blot assays to ascertain the underlying mechanism by which CA125 stimulates cell migration via the SGK3/FOXO3 pathway. Anti-mesothelin antibodies (anti-MSLN) were used to block CA125 stimulation. Then the expression levels of DKK1were tested by enzyme-linked immunosorbent assay (ELISA) to eliminate the blocking effect of anti-MSLN to CA125 stimulation. Xenograft mouse models were used to detect the effects of CA125 and anti-MSLN on ovarian cancer metastasis . DKK1 levels were downregulated in ovarian tumor tissues according to the analyses of two databases and significantly correlated with FIGO stage, grade and disease-free survival in ovarian cancer patients. DKK1 levels were downregulated by CA125 stimulation . Overexpression of DKK1 reversed the ability of exogenous CA125 to mediate cell migration by activating the SGK3/FOXO3 signaling pathway. Anti-MSLN abrogated the DKK1 reduction and increased the apoptosis of ovarian cancer cells. The use of anti-MSLN in xenograft mouse models significantly reduced tumor growth and metastasis accelerated by CA125. These experiments revealed that the SGK3/FOXO3 pathway was activated, wherein decreased expression of DKK1 was caused by CA125, which fuels ovarian cancer cell migration. Mesothelin is a potential therapeutic target for the treatment of ovarian cancer metastasis.
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http://dx.doi.org/10.7150/ijbs.52097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893585PMC
January 2021

CRS-related coagulopathy in BCMA targeted CAR-T therapy: a retrospective analysis in a phase I/II clinical trial.

Bone Marrow Transplant 2021 Feb 19. Epub 2021 Feb 19.

Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) has shown promising effects in the treatment of patients with refractory/relapsed multiple myeloma (R/R MM) patients. In this retrospective analysis of phase I/II clinical trial (ChiCTR1800017404), 37 patients with R/R MM received their first BCMA-targeted CAR T-cells following lymphodepletion chemotherapy. The response rate was high (97%), while accompanied by a high incidence of adverse events including coagulation dysfunction. Of 37 patients, all (100%) had cytokine release syndrome (CRS) and 34 (91%) developed at least one abnormal coagulation parameter. The values of coagulation parameters were positively correlated with the severity of CRS as well as with the levels of some cytokines, such as interleukin (IL)-6, IL-10, and interferon (IFN)-γ, etc. Furthermore, levels of the plasma tissue factor (TF), Factor X (FX), Factor XII (FXII), and P-selectin also showed a positive correlation with severity of CRS as well as some specific cytokines, which indicates that these factors are likely to play important roles in CRS-related coagulopathy. Our study suggests that there exists relationship in some extent between coagulation disorder and CRS. Moreover, coagulation dysfunction can be managed with daily monitoring and early intervention despite high incidence.
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http://dx.doi.org/10.1038/s41409-021-01226-9DOI Listing
February 2021

Clinical Utility of Circulating Cell-free DNA Mutations in Anaplastic Thyroid Carcinoma.

Thyroid 2021 Feb 18. Epub 2021 Feb 18.

University of Texas MD Anderson Cancer Center, 4002, Department of Endocrine Neoplasia and Hormonal Disorders, Houston, Texas, United States;

Background: Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid cancer that requires a rapid diagnosis and treatment to achieve disease control. Gene mutation profiling of circulating cell free DNA (cfDNA) in peripheral blood may help to facilitate early diagnosis and treatment selection. The relatively rapid turnaround time compared to conventional tumor mutation testing is a major advantage. The objectives of this study were to examine the concordance of ATC-related mutations detected in cfDNA with those detected in the corresponding tumor tissue, and to determine the prognostic significance of cfDNA mutations in ATC patients.

Methods: ATC patients who were diagnosed and treated at The University of Texas MD Anderson Cancer Center between January 2015 and February 2018 and who had cfDNA testing were included in this study. cfDNA was collected by blood draw and was analyzed by next generation sequencing (NGS) using the Guardant360- 73 gene platform.

Results: A total of 87 patients were included in the study. The most frequently mutated genes detected in cfDNA were TP53, BRAF and PIK3CA. In 28 treatment naive ATC patients, the concordance rate of detected mutations in TP53, BRAF V600E and PIK3CA between cfDNA and matched tissue NGS was 82.1%, 92.9% and 92.9% respectively. Patients with a PIK3CA mutation detected on cfDNA had worse overall survival (p=0.03). This association was observed across various treatment modalities including surgery, cytotoxic chemotherapy, radiation and BRAF inhibitor therapy. With regard to treatment, BRAF inhibitor therapy significantly improved ATC overall survival (p=0.003).

Conclusions: cfDNA is a valuable tool to evaluate a tumor's molecular profile in ATC patients. We identified high concordance rates between the gene mutations identified via cfDNA analysis and those identified from the NGS of the corresponding tumor tissue sequencing. Identified mutations in cfDNA can potentially provide timely information to guide treatment selection and evaluate the prognosis in ATC patients.
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http://dx.doi.org/10.1089/thy.2020.0296DOI Listing
February 2021

Macrophage-derived netrin-1 contributes to endometriosis-associated pain.

Ann Transl Med 2021 Jan;9(1):29

Department of Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Endometriosis-associated pain can be considered a type of neuropathic pain. Netrin-1 is an axon guidance cue that regulates axonal attraction or rejection in neural injury and regeneration. However, whether netrin-1 plays a role in endometriosis-associated pain remains unclear. This study aimed to determine the role of netrin-1 in endometriosis-related pain.

Methods: Peripheral blood, peritoneal fluid, and endometrial tissues were sampled from women with (n=37) and without endometriosis (n=23). Lipopolysaccharide (LPS) and interferon gamma (IFN-γ) were used to stimulate human monocytic cell lines (THP-1) and rat alveolar macrophage-derived cell lines (NR8383) to induce M1 phenotype macrophages. Serum netrin-1 concentrations, endometrial expression levels of netrin-1, and its receptors including deleted in colorectal cancer (DCC), A2B adenosine receptor (A2BAR), uncoordinated B receptor (UNC5B), uncoordinated C receptor (UNC5C) and Down's syndrome cell adhesion molecule (DSCAM) were assessed. The polarization phenotypes of the peritoneal macrophages were identified by detecting the marker expression of M1/M2 macrophages via flow cytometry. The expression levels of M1 markers and netrin-1 in THP-1/NR8383 cells were determined.

Results: The expression levels of netrin-1 in serum and endometriotic lesions were significantly higher in women with endometriosis, and were positively correlated with the severity of endometriosis-associated pain. Netrin-1 was co-expressed with CD68 (a macrophage marker) in endometriotic lesions and was synthesized and secreted by THP-1 and NR8383 cells in the process of M1 polarization. In women with endometriosis, peritoneal macrophages were polarized towards the M1 phenotype. In addition, increased expression of DCC and A2BAR, and decreased expression of UNC5B, UNC5C and DSCAM were found in endometriotic lesions.

Conclusions: These results suggest that netrin-1 production by macrophages in endometriotic lesions may play an important role in endometriosis-associated pain.
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http://dx.doi.org/10.21037/atm-20-2161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859736PMC
January 2021

Combination of Microneedles and MF59 Adjuvant as a Simple Approach to Enhance Transcutaneous Immunization.

J Biomed Nanotechnol 2020 Dec;16(12):1776-1786

MF59, an oil-in-water nanoemulsion, has been used in licensed seasonal influenza vaccines for many years. Administration of such vaccines by injection is associated with pain and safety issues. Here, we evaluated the potential of administering MF59 via a transcutaneous route with antigen loading (either encapsulated into or mixed with MF59) to intact or microneedle-pretreated skin. In addition to commercial MF59, we also prepared a nanoemulsion to encapsulate hydrophilic antigens by mimicking the formulation and preparation technique of MF59. The nanoemulsion was prepared using a water-in-oil-in-water emulsion method, and was similar to MF59 in composition, particle size, and morphology. Compared with the intact skin group, the microneedle-pretreated group showed significant enhanced antigen penetration. transcutaneous immunization analysis showed that the MF59-adjuvant influenza vaccine elicited approximately 3-5 times higher hemagglutination inhibition titers than the influenza solution alone in BALB/c mice after microneedle pretreatment. The intact skin group showed negative immune results at the same dose, suggesting that microneedle pretreatment was critical for efficient delivery of antigens, to obtain strong immune responses. Furthermore, the loading method (encapsulation or mixing with the vehicle) did not affect the dermal penetration or transcutaneous immunization of antigens on microneedle-pretreated skin. Moreover, cellular assays showed that MF59 facilitated the maturation of dendritic cells and enhanced antigen uptake by antigen-presenting cells. In conclusion, the combination of microneedle pretreatment and mixing of MF59 with antigen provides a simple approach to enhance transcutaneous immunization.
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http://dx.doi.org/10.1166/jbn.2020.3007DOI Listing
December 2020

Identification of the first glyphosate-resistant capeweed (Arctotheca calendula) population.

Pest Manag Sci 2021 May 10;77(5):2568-2575. Epub 2021 Feb 10.

Australian Herbicide Resistance Initiative (AHRI), School of Agriculture and Environment, The University of Western Australia, Perth, WA, Australia.

Background: Glyphosate is routinely used in Australia to control the Arctotheca species Arctotheca calendula (L.) Levyns (referred hereinafter as capeweed). This study identifies the first global case of field-evolved glyphosate-resistant capeweed, collected from the grainbelt of Western Australia.

Results: In 2020, a capeweed biotype that was collected from Borden in the southern Western Australian grainbelt was confirmed to be glyphosate-resistant (referred hereinafter as Spence population). When compared to the pooled mortality of six field-collected, glyphosate susceptible capeweed populations (S1, S2, S3, S4, S5 and S6), the Spence population was found > 11-fold more resistant to glyphosate than the pooled results of the susceptible populations (S1-S6) at the lethal dose of 50% (LD ) level. The growth of the Spence population was also less affected, requiring > 13-fold more glyphosate to reduce growth than the pooled susceptible populations at the growth reduction of 50% (GR ) level. Sequencing of the plastidic 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene indicated no known single gene mutation imparting glyphosate resistance. This study, however, did not investigate any other known mechanisms that impart glyphosate resistance. When screened at the field-applied rate, this Spence population was also found to survive an inhibitor of acetolactate synthase (ALS) (metosulam) and an inhibitor of phytoene desaturase (diflufenican).

Conclusions: This is the first confirmation of glyphosate resistance evolution in a capeweed population globally. With capeweed resistance already confirmed to photosystem-I inhibiting herbicides (paraquat and diquat), this study emphasizes the importance of using integrated measures that do not depend only on the use of non-selective herbicides for controlling herbicide resistance-prone capeweed populations. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.6295DOI Listing
May 2021

A convolutional recurrent neural network with attention framework for speech separation in monaural recordings.

Sci Rep 2021 Jan 14;11(1):1434. Epub 2021 Jan 14.

College of Electrical Engineering, Sichuan University, Chengdu, 610065, China.

Most speech separation studies in monaural channel use only a single type of network, and the separation effect is typically not satisfactory, posing difficulties for high quality speech separation. In this study, we propose a convolutional recurrent neural network with an attention (CRNN-A) framework for speech separation, fusing advantages of two networks together. The proposed separation framework uses a convolutional neural network (CNN) as the front-end of a recurrent neural network (RNN), alleviating the problem that a sole RNN cannot effectively learn the necessary features. This framework makes use of the translation invariance provided by CNN to extract information without modifying the original signals. Within the supplemented CNN, two different convolution kernels are designed to capture information in both the time and frequency domains of the input spectrogram. After concatenating the time-domain and the frequency-domain feature maps, the feature information of speech is exploited through consecutive convolutional layers. Finally, the feature map learned from the front-end CNN is combined with the original spectrogram and is sent to the back-end RNN. Further, the attention mechanism is further incorporated, focusing on the relationship among different feature maps. The effectiveness of the proposed method is evaluated on the standard dataset MIR-1K and the results prove that the proposed method outperforms the baseline RNN and other popular speech separation methods, in terms of GNSDR (gloabl normalised source-to-distortion ratio), GSIR (global source-to-interferences ratio), and GSAR (gloabl source-to-artifacts ratio). In summary, the proposed CRNN-A framework can effectively combine the advantages of CNN and RNN, and further optimise the separation performance via the attention mechanism. The proposed framework can shed a new light on speech separation, speech enhancement, and other related fields.
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http://dx.doi.org/10.1038/s41598-020-80713-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809293PMC
January 2021

The Ile-2041-Val mutation in the ACCase gene confers resistance to clodinafop-propargyl in American sloughgrass (Beckmannia syzigachne Steud).

Pest Manag Sci 2021 May 27;77(5):2425-2432. Epub 2021 Jan 27.

College of Plant Protection, Hunan Agricultural University, Changsha, 410128, China.

Background: Exploring the mechanisms of herbicide resistance in weeds is an important part of designing resistance management strategies and rationalizing herbicide use. Beckmannia syzigachne is one of the most important agricultural weeds in China. Long-term use of acetyl-CoA carboxylase (ACCase)-inhibiting herbicides has led to the evolution of herbicide resistance in B. syzigachne. ACCase-inhibiting herbicides comprise three chemical families: aryloxyphenoxypropionates (APPs), cyclohexanediones (CHDs) and phenylpyraxoline (DENs).

Results: Based on whole-plant dose-response experiments, a B. syzigachne population (BS-R) was confirmed to be 12- and 20-fold resistant to the APP herbicides quizalofop-P-ethyl and clodinafop-propargyl, and 2.2-, 2.8- and 2.8-fold resistant to fenoxaprop-P-ethyl, the CHD herbicide sethoxydim and the PPZ herbicide pinoxaden, respectively, compared with its susceptible counterpart (BS-S). Resistance to clodinafop-propargyl in the BS-R population could not be reversed by the known cytochrome P450 (CYP450) inhibitor malathion and the glutathione S-transferase (GST) inhibitor 4-chloro-7-nitrobenzoxadiazole. In addition, no difference in CYP450 and GST activity was confirmed between the BS-R and BS-S populations. ACCase gene sequencing revealed an Ile-2041-Val mutation in the BS-R population. A derived cleaved amplified polymorphic sequence marker was developed for rapid detection of the specific Ile-2041-Val mutation. Correlation quantification of resistance in homo- and hetero-resistant versus wild-type plants showed that resistance to clodinafop-propargyl in this population is conferred by the Ile-2041-Val mutation.

Conclusion: Unlike previous reports on the unique cross-resistance pattern conferred by the 2041 mutation, this study demonstrates that the Ile-2041-Val mutation in BS-R population confers resistance to certain ACCase-inhibiting APP, CHD and PPZ herbicides in B. syzigachne. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.6271DOI Listing
May 2021

Droplet-based mRNA sequencing of fixed and permeabilized cells by CLInt-seq allows for antigen-specific TCR cloning.

Proc Natl Acad Sci U S A 2021 Jan;118(3)

Molecular Biology Institute, University of California, Los Angeles, CA 90095;

T cell receptors (TCRs) are generated by somatic recombination of V/D/J segments to produce up to 10 unique sequences. Highly sensitive and specific techniques are required to isolate and identify the rare TCR sequences that respond to antigens of interest. Here, we describe the use of mRNA sequencing via cross-linker regulated intracellular phenotype (CLInt-Seq) for efficient recovery of antigen-specific TCRs in cells stained for combinations of intracellular proteins such as cytokines or transcription factors. This method enables high-throughput identification and isolation of low-frequency TCRs specific for any antigen. As a proof of principle, intracellular staining for TNFα and IFNγ identified cytomegalovirus (CMV)- and Epstein-Barr virus (EBV)-reactive TCRs with efficiencies similar to state-of-the-art peptide-MHC multimer methodology. In a separate experiment, regulatory T cells were profiled based on intracellular FOXP3 staining, demonstrating the ability to examine phenotypes based on transcription factors. We further optimized the intracellular staining conditions to use a chemically cleavable primary amine cross-linker compatible with current single-cell sequencing technology. CLInt-Seq for TNFα and IFNγ performed similarly to isolation with multimer staining for EBV-reactive TCRs. We anticipate CLInt-Seq will enable droplet-based single-cell mRNA analysis from any tissue where minor populations need to be isolated by intracellular markers.
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http://dx.doi.org/10.1073/pnas.2021190118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826406PMC
January 2021

Implications of the microbiome in the development and treatment of pancreatic cancer: Thinking outside of the box by looking inside the gut.

Neoplasia 2021 02 6;23(2):246-256. Epub 2021 Jan 6.

Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA; Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL, USA. Electronic address:

Pancreatic ductal adenocarcinoma is the third leading cause of cancer-related death in the United States. As one of the most lethal cancer types, the prognosis for patients diagnosed with pancreatic cancer remains dismal and novel investigations are urgently needed. Evidence for an association of microbes with pancreatic cancer risk, development, treatment response, and post-treatment survivorship is rapidly developing. Herein, we provide an overview on the role of the microbiome as it relates to the natural history of pancreatic cancer, including host immune interactions, alterations in metabolism, direct carcinogenic effect, and its role in treatment response.
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http://dx.doi.org/10.1016/j.neo.2020.12.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804346PMC
February 2021

Recepteur d'origine nantais contributes to the development of endometriosis via promoting epithelial-mesenchymal transition of a endometrial epithelial cells.

J Cell Mol Med 2021 Feb 6;25(3):1601-1612. Epub 2021 Jan 6.

Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Endometriosis is a benign, chronic inflammatory disease that commonly occurs in reproductive-aged women. Epithelial-mesenchymal transition (EMT) of endometrial epithelial cells plays an important role in the development of endometriosis. Recepteur d'origine nantais (RON), a receptor tyrosine kinase, has been reported to promote EMT and progression in tumours. However, whether and how RON mediates the EMT and endometriosis development is not known. Here, we found that RON activation could improve the migratory and invasive capabilities, change cellular morphologies, and decrease expression of E-cadherin and increase expression of N-cadherin in endometrial epithelial cells. Inhibition or knockdown of RON expression suppressed the migration and invasion of endometrial epithelial cells. Our studies also indicated that RON played its part in endometrial epithelial cells through protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) pathways. Treatment with a RON inhibitor could decrease the number of ectopic lesions in a mouse model of endometriosis and mediate expression of EMT markers in endometriotic lesions. These data suggest that RON contributed to endometriosis development by promoting EMT of endometrial epithelial cells. Therefore, RON may be a new therapeutic target for endometriosis.
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http://dx.doi.org/10.1111/jcmm.16261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875913PMC
February 2021

Changes in planktonic and sediment bacterial communities under the highly regulated dam in the mid-part of the Three Gorges Reservoir.

Appl Microbiol Biotechnol 2021 Jan 6;105(2):839-852. Epub 2021 Jan 6.

Key Laboratory of Reservoir Aquatic Environment, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China.

Bacterial communities play an important role in the biogeochemical cycle in reservoir ecosystems. However, the dynamic changes in both planktonic and sediment bacterial communities in a highly regulated dam reservoir remain unclear. This study investigated the temporal distribution patterns of bacterial communities in a transition section of the Three Gorges Reservoir (TGR) using Illumina MiSeq sequencing. Results suggested that in comparison to the planktonic bacteria, sediment bacteria contributed more to the reservoir microbial communities, accounting for 97% of the 7434 OTUs. The Shannon diversity index in the water (3.22~5.68) was generally lower than that in the sediment (6.72~7.56). In the high water level period (January and March), Proteobacteria, Actinobacteria, Cyanobacteria, and Firmicutes were the most abundant phyla, whereas in the low water level period (May, July, and September), the dominant phyla were Proteobacteria, Actinobacteria, and Bacteroidetes. Sediment samples were dominated by Proteobacteria, Chloroflexi, and Acidobacteria. Principal coordinate analysis of the bacterioplankton communities showed greater sensitivity to monthly changes than that of the sediment bacterial communities. Network analysis suggested that in comparison to planktonic bacterial communities, sediment bacterial communities were more complex and stable. The linear relationship between the CH/CO ratio, water level, and relative abundance of methanotrophs highlighted the potential methane-oxidizing process in the mid-part of the TGR. Moreover, the potential impact of dam regulation on the bacterial communities was revealed by the significant relationship between abundant phyla and the inflow of the TGR. KEY POINTS: • Bacterioplankton communities showed great sensitivity to monthly changes. • Potential methane-oxidizing process was revealed in this representative area. • Water inflow regulated by dam has significant effects on dominant bacterioplankton.
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http://dx.doi.org/10.1007/s00253-020-11047-3DOI Listing
January 2021