Publications by authors named "Yu Ma"

790 Publications

Effect of propiconazole on neutrophil extracellular traps formation: Assessing the role of autophagy.

Food Chem Toxicol 2022 Aug 8:113354. Epub 2022 Aug 8.

Xiangya School of Public Health, Central South University, Changsha, 410078, PR China. Electronic address:

Propiconazole (Pcz) is a kind of triazole fungicide which has an important impact on the environment. With the extensive use of Pcz in agricultural production activities, the pesticides are left in soil, water, crops and food, and will enter the organisms in the form of residues. Neutrophils play a key role in the body's innate immunity against pathogens, and the formation of neutrophil extracellular traps (NETs) is an important way for neutrophils to exert their immune function. In the present study, we focused on the effect of Pcz on the NETs of Sprague-Dawley (SD) rats for the first time. Our data demonstrated that Pcz could hinder NETs formation via inhibiting the Phosphoinositide 3-kinase (PI3K)/rapidly accelerated fibrosarcoma (Raf)/extracellular signal-regulated kinase (ERK) signaling. In the meanwhile, we assessed the role of autophagy played in this process and revealed that Pcz may inhibit the respiratory burst in neutrophils. This study provided new insights into the immunotoxic hazards of Pcz and additional laboratory evidence for assessing the impact of Pcz on terrestrial organisms.
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http://dx.doi.org/10.1016/j.fct.2022.113354DOI Listing
August 2022

Fucoxanthin Prevents the Ovalbumin-Induced Food Allergic Response by Enhancing the Intestinal Epithelial Barrier and Regulating the Intestinal Flora.

J Agric Food Chem 2022 Aug 10. Epub 2022 Aug 10.

College of Ocean Food and Biological Engineering, Jimei University, Xiamen, Fujian 361021, China.

This study aimed to determine whether fucoxanthin alleviated ovalbumin (OVA)-induced food allergy (FA) and explored the possible mechanisms. The results indicated that supplementation with fucoxanthin at 10.0-20.0 mg/kg per day for 7 weeks inhibited food anaphylaxis and the production of immunoglobulin (Ig) E, IgG, histamine, and related cytokines while alleviating allergic symptoms in sensitized mice. Fucoxanthin enhanced the intestinal epithelial barrier by up-regulating tight junction (TJ) protein expression and promoting regenerating islet-derived protein III-gamma (RegIIIγ) and secretory IgA (sIgA) secretion. In addition, fucoxanthin induced the secretion of anti-inflammatory factors (interleukin (IL)-10 and transforming growth factor β (TGF-β)) by regulatory T (Treg) cells and decreased the pro-inflammatory factor levels (IL-4, tumor necrosis factor-α (TNF-α), IL-17, and IL-1β), ameliorating intestinal inflammation. Compared with the model group, beneficial bacteria, such as Lactobacillaceae, increased in the intestinal flora, while pathogenic bacteria like Helicobacteraceae, Desulfovibrionaceae, and Streptococcaceae decreased. Therefore, fucoxanthin may effectively prevent FA by enhancing the intestinal epithelial barrier and reshaping the intestinal flora.
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http://dx.doi.org/10.1021/acs.jafc.2c04685DOI Listing
August 2022

Low molecular weight protein phosphatase APH mediates tyrosine dephosphorylation and ABA response in Arabidopsis.

Stress Biol 2022 18;2(1):23. Epub 2022 May 18.

Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai, 200032 China.

Low molecular weight protein tyrosine phosphatase (LWM-PTP), also known as acid phosphatase, is a highly conserved tyrosine phosphatase in living organisms. However, the function of LWM-PTP homolog has not been reported yet in plants. Here, we revealed a homolog of acid phosphatase, APH, in Arabidopsis plants, is a functional protein tyrosine phosphatase. The mutants are hyposensitive to ABA in post-germination growth. We performed an anti-phosphotyrosine antibody-based quantitative phosphoproteomics in wild-type and mutant and identified hundreds of putative targets of APH, including multiple splicing factors and other transcriptional regulators. Consistently, RNA-seq analysis revealed that the expression of ABA-highly-responsive genes is suppressed in mutants. Thus, APH regulates the ABA-responsive gene expressions by regulating the tyrosine phosphorylation of multiple splicing factors and other post-transcriptional regulators. We also revealed that Tyr383 in RAF9, a member of B2 and B3 RAF kinases that phosphorylate and activate SnRK2s in the ABA signaling pathway, is a direct target site of APH. Phosphorylation of Tyr383 is essential for RAF9 activity. Our results uncovered a crucial function of APH in ABA-induced tyrosine phosphorylation in Arabidopsis.

Supplementary Information: The online version contains supplementary material available at 10.1007/s44154-022-00041-6.
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http://dx.doi.org/10.1007/s44154-022-00041-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345830PMC
May 2022

Design of fusion enzymes for biocatalytic applications in aqueous and non-aqueous media.

Front Bioeng Biotechnol 2022 22;10:944226. Epub 2022 Jul 22.

Biocatalysis and Bioprocessing Group, Department of Biological and Chemical Engineering, Aarhus University, Aarhus, Denmark.

Biocatalytic cascades play a fundamental role in sustainable chemical synthesis. Fusion enzymes are one of the powerful toolboxes to enable the tailored combination of multiple enzymes for efficient cooperative cascades. Especially, this approach offers a substantial potential for the practical application of cofactor-dependent oxidoreductases by forming cofactor self-sufficient cascades. Adequate cofactor recycling while keeping the oxidized/reduced cofactor in a confined microenvironment benefits from the fusion fashion and makes the use of oxidoreductases in harsh non-aqueous media practical. In this mini-review, we have summarized the application of various fusion enzymes in aqueous and non-aqueous media with a focus on the discussion of linker design within oxidoreductases. The design and properties of the reported linkers have been reviewed in detail. Besides, the substrate loadings in these studies have been listed to showcase one of the key limitations (low solubility of hydrophobic substrates) of aqueous biocatalysis when it comes to efficiency and economic feasibility. Therefore, a straightforward strategy of applying non-aqueous media has been briefly discussed while the potential of using the fusion oxidoreductase of interest in organic media was highlighted.
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http://dx.doi.org/10.3389/fbioe.2022.944226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354712PMC
July 2022

Human activities induce potential aquatic threats of micropollutants in Danjiangkou Reservoir, the largest artificial freshwater lake in Asia.

Sci Total Environ 2022 Aug 4:157843. Epub 2022 Aug 4.

College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China. Electronic address:

Freshwater biodiversity and ecosystem services may decline because of toxicant input, and other environmental variables often co-occur with contaminants to jeopardize the freshwater ecosystem. In this study, Danjiangkou Reservoir (DJKR) in central China was selected as the target research area to investigate the impact of multiple categories of micropollutants coupled with other stressors on the reservoir ecosystem. A total of 140 samples were collected from 28 sites in DJKR, and 124 micropollutants, including pesticides, organophosphate esters (OPEs), psychoactive substances, antiviral drugs, and pharmaceutical and personal care products, were quantified. A total of 108 micropollutants were detected in the water samples, with sum concentrations ranging from 82.35 ng·L to 1436.57 ng·L, and 71 of them had a detection frequency above 50 %, indicating the prevailing micropollutant contamination in the reservoir. The most severe pollution and risks were observed in the tributaries of DJKR. Pesticides (neonicotinoid and triazine) and OPEs were the major contributors to the ecological risk in the reservoir. Insecticides, herbicides, and OPEs accounted for the majority of the risks to fish, algae, and invertebrates, respectively. The determined priority pollutants should be paid increased attention. Environmental variables and human activities, such as human land use, induced the potential aquatic threats of micropollutants in DJKR. Results demonstrated that micropollutant pollution was one of the dominant pressures faced by aquatic organisms and human beings, and human activities played important roles as well.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157843DOI Listing
August 2022

Interactions between suspended sediments and submerged macrophytes-epiphytic biofilms under water flow in shallow lakes.

Water Res 2022 Jul 26;222:118911. Epub 2022 Jul 26.

Ministry of Education Key Laboratory of Integrated Regulation and Resource Development on Shallow Lakes, Ministry of Education, Hohai University, Nanjing 210098, China; College of Environment, Hohai University, Nanjing 210098, P. R. China.

Suspended sediments (SS) pollution is one of the factors affecting the transfer from turbid water state to clear water state in shallow lakes. However, the interactions between suspended sediments and submerged plants are far from clear. In this study, we investigated the settlement laws of SS in overlying water and its impact on the epiphytic biofilm of Myriophyllum verticillatum and Vallisneria natans under water flow. At least 90% of turbidity can be removed from overlying water, and the decreasing trend of water turbidity fitted the logarithmic decay model in all treatments. The size distribution of SS fit the log-normal distribution model in the first 240 min after SS addition. It should be noted that the main peak particle sizes were lower in treatments with submerged macrophytes (8.71-13.18 μm) than without plants (15.14-19.95 μm). Water flow and SS addition significantly increased the thickness of biofilms attached to M. verticillatum (p < 0.05), but they together significantly reduced the biofilm thickness on V. natans (p < 0.05). SS increased the bacterial α-diversity but decreased eukaryotic one in epiphytic biofilms. However, water flow had a more significant impact on microbial communities (especially eukaryotes) than SS and plant species. The relative abundances of dominant phylum Proteobacteria, class Alphaproteobacteria and Betaproteobacteria, and class Verrucomicrobiae increased in epiphytic biofilms after SS addition. Co-occurrence networks reveal that photosynthetic microbes in epiphytic biofilms played an important role in microbial communities under water flow and SS, and many hub microbes were increased by SS addition but reduced by water flow. These data highlight that SS decline can be predicted by the logarithmic decay model and, SS and water flow can affect the epiphytic-biofilm on submerged macrophytes.
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http://dx.doi.org/10.1016/j.watres.2022.118911DOI Listing
July 2022

Foxp2 inhibits Th9 cell differentiation and attenuates allergic airway inflammation in a mouse model of ovalbumin-induced asthma.

Int Immunopharmacol 2022 Aug 2;111:109060. Epub 2022 Aug 2.

Department of Respiratory Medicine, Children's Hospital of Soochow University, Suzhou 215003, China. Electronic address:

This study aimed to explore the effects of forkhead box P2 gene (Foxp2) on T-helper 9 (Th9) differentiation in asthmatic mice. An in vivo asthmatic mouse model was induced with ovalbumin (OVA). An in vitro model was established by culturing CD4 T cells with TGF-β, IL-4, and anti-IFN-γ. ELISA, flow cytometry, qRT-PCR and Western blot were performed to examine IL-9 secretion, Th9 cell number, and Th9 cell transcription factor expression, respectively. Pathological changes in lung tissues and airway mucus secretion were assessed with HE and PAS glycogen staining. Anti-IL-9 mAb reversed the elevation in Th9 cells and IL-9 expression in lung tissues and bronchoalveolar lavage fluid (BALF) of asthmatic mice. Foxp2 was downregulated in BALF and lung tissue of asthmatic mice and Th9 cells. Overexpression of Foxp2 inhibited Th9 cell differentiation in vitro and improved airway inflammation in vivo. Our study suggests that overexpression of Foxp2 attenuates allergic asthma by inhibiting Th9 cell differentiation.
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http://dx.doi.org/10.1016/j.intimp.2022.109060DOI Listing
August 2022

The long noncoding RNA HOXA11-AS promotes lung adenocarcinoma proliferation and glycolysis via the microRNA-148b-3p/PKM2 axis.

Cancer Med 2022 Aug 4. Epub 2022 Aug 4.

Department of Nuclear Medicine, The First Hospital of China Medical University, Shenyang, China.

Background: Lung cancer is the most common malignancy in the world and a growing number of researches have focused on its metabolic characteristics. Studies have shown that the long non-coding RNA (lncRNA) HOXA11-AS is aberrantly expressed in many tumors. However, the role of HOXA11-AS in lung adenocarcinoma (LUAD) glycolysis and other energy metabolism pathways has not been characterized.

Method: The mRNA levels of HOXA11-AS, microRNA-148b-3p (miR-148b-3p), and pyruvate kinase M2 (PKM2) were detected using qRT-PCR. The expression levels of proteins were measured using immunohistochemistry and western blot. The CCK-8, EdU, and colony formation assays were used to assess proliferation. Glycolytic changes were assessed by measuring lactate production, ATP production, and F-FDG uptake. Bioinformatics analysis and dual-luciferase reporter assays were used to characterize the relationship between HOXA11-AS, miR-148b-3p, and PKM2. Proliferation and glycolytic changes were analyzed in xenograft tumor experiments using Micro-PET imaging after downregulation of HOXA11-AS in vivo.

Results: The expression of HOXA11-AS was markedly increased in LUAD, and was strongly associated with a poor prognosis. In addition, HOXA11-AS promoted proliferation and glycolysis in LUAD, and miR-148b-3p inhibited proliferation and glycolysis in LUAD. Mechanistically, HOXA11-AS positively regulated PKM2 expression by binding to miR-148b-3p, thereby promoting LUAD proliferation and glycolysis. In addition, HOXA11-AS inhibited LUAD xenograft growth and glycolysis via upregulation of miR-148b-3p expression and downregulation of PKM2 expression in vivo.

Conclusions: These results showed that HOXA11-AS enhanced LUAD proliferation and glycolysis via the miR-148b-3p/PKM2 axis. The findings in this paper expanded our understanding of the molecular mechanisms of LUAD tumorigenesis and glycolysis and showed that HOXA11-AS could be useful as a diagnostic and prognostic marker for LUAD. F-FDG PET/CT can be used to visually evaluate the therapeutic effect of targeting HOXA11-AS.
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http://dx.doi.org/10.1002/cam4.5103DOI Listing
August 2022

Effects of High Ammonium Loading on Two Submersed Macrophytes of Different Growth Form Based on an 18-Month Pond Experiment.

Front Plant Sci 2022 14;13:939589. Epub 2022 Jul 14.

Department of Ecoscience, WATEC, Aarhus University, Aarhus, Denmark.

Ammonium (NH-N) produces a paradoxical effect on submersed macrophytes because it is not only the preferred nitrogen source for the growth of plants but also threatens the growth of plants at high concentration. Whether short-term and small-scale physiological toxicity experiments at an individual level can reflect the effects of high ammonium on populations of submersed macrophytes in natural conditions is still unclear. In this study, an 18-month experiment was conducted in six 600 m ponds subjected to different levels of ammonium loading. The effects of high ammonium on populations of canopy-forming and rosette-forming were explored. The results showed that and populations can develop high cover and height at high ammonium concentration (7 mg/L) at short-term exposures, and may be tolerant to 18 mg/L ammonium concentration. However, the cover of and the height of both species were inhibited at 2.4 mg/L at long-term exposures. The height of was two to six times higher than that of across all treatments and control by the end of the experiment, and the cover of was 7-11 times higher than that of in most NH-N loading treatments, except the cover of in the highest NH-N loading treatment with 18 mg/L NH-N. The rosette-forming resists ammonium stress by slow growth (shoot elongation) to reduce consumption, while canopy-forming species resist ammonium stress by shoot elongation and canopy development to capture light. Although increasing ammonium concentration may induce severe stress on , the morphological characteristics of this species may, to some extent, release the plants from this stress. Our present study indicates that the negative effects of ammonium stress on the development of populations increased with exposure duration, and the submersed macrophyte community with stronger ability for light capture and dispersal may resist high ammonium stress. Nevertheless, in strongly ammonium-enriched systems, competition and succession cannot be neglected.
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http://dx.doi.org/10.3389/fpls.2022.939589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330597PMC
July 2022

Ratiometric Fluorescent pH Sensor Based on a Tunable Multivariate Covalent Organic Framework.

Anal Chem 2022 Aug 26;94(31):11062-11069. Epub 2022 Jul 26.

College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institutes of Biomedical Sciences, Shandong Normal University, Jinan 250014, P.R. China.

Ratiometric detection of pH is always significant in environmental regulation, medical diagnosis, synthetic chemistry, and beyond. The construction of practical ratiometric pH sensors with reusability is still challenging. Herein, by exploiting a multivariate strategy, we first synthesized and reported a series of novel three-component covalent organic frameworks (COF-COOH, = 33, 50, and 67) through Schiff base reaction between 2-hydroxybenzene-1,3,5-tricarbaldehyde (HTA), 4,4'-diamino-3,3'-biphenyldicarboxylic acid (DBA), and 5,5'-diamino-2,2'-bipyridine (BPY) at various molar ratios ( = [DBA]/([BPY] + [DBA]) × 100 = 33, 50, and 67). COF-COOH ( = 33, 50, and 67) displayed ratiometric pH sensing performance in acidic conditions with selectivity and repeatability. By tuning the molar ratio of DBA and BPY, the fluorescent properties, linear pH responsive ranges, and p values of COF-COOH ( = 33, 50, and 67) can be regulated. Meanwhile, the two-component COF-COOH and COF-COOH did not exhibit ratiometric pH detection ability. Moreover, the constructed three ratiometric sensors can be applied to detect pH in drug solutions and carbonated drinks with satisfactory results. This work sheds new light on the design and fabrication of innovative ratiometric fluorescent sensors using COFs.
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http://dx.doi.org/10.1021/acs.analchem.2c01999DOI Listing
August 2022

An analgesic peptide H-20 attenuates chronic pain via the PD-1 pathway with few adverse effects.

Proc Natl Acad Sci U S A 2022 Aug 25;119(31):e2204114119. Epub 2022 Jul 25.

Center for Basic Medical Research, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China.

The lack of effective and safe analgesics for chronic pain management has been a health problem associated with people's livelihoods for many years. Analgesic peptides have recently shown significant therapeutic potential, as they are devoid of opioid-related adverse effects. Programmed cell death protein 1 (PD-1) is widely expressed in neurons. Activation of PD-1 by PD-L1 modulates neuronal excitability and evokes significant analgesic effects, making it a promising target for pain treatment. However, the research and development of small molecule analgesic peptides targeting PD-1 have not been reported. Here, we screened the peptide H-20 using high-throughput screening. The in vitro data demonstrated that H-20 binds to PD-1 with micromolar affinity, evokes Src homology 2 domain-containing tyrosine phosphatase 1 (SHP-1) phosphorylation, and diminishes nociceptive signals in dorsal root ganglion (DRG) neurons. Preemptive treatment with H-20 effectively attenuates perceived pain in naïve WT mice. Spinal H-20 administration displayed effective and longer-lasting analgesia in multiple preclinical pain models with a reduction in or absence of tolerance, abuse liability, constipation, itch, and motor coordination impairment. In summary, our findings reveal that H-20 is a promising candidate drug that ameliorates chronic pain in the clinic.
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http://dx.doi.org/10.1073/pnas.2204114119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351488PMC
August 2022

Plant regeneration via callus-mediated organogenesis in commercial variety of Chuanbeichai No. 1 in DC.

Plant Biotechnol Rep 2022 Jul 16:1-11. Epub 2022 Jul 16.

School of Life Science and Engineering, Southwest University of Science and Technology, 59 Qinglong Road, Mianyang, 621010 Sichuan China.

DC is an important medicinal plant with many active ingredients that are used for the treatment of different types of diseases and valued in pharmaceutical markets. In vitro shoot regeneration can efficiently contribute to the improvement of In the present study, we investigated the effects of the explant type and plant growth regulators (PGRs) on embryogenic callus induction and plant regeneration in . Our investigation demonstrated that 2 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) combined with 1 mg/L thidiazuron (TDZ) played a major role in promoting callus induction from leaf, hypocotyl and stem 2 explants, whereas the most effective treatment for stem 1 callus formation was Murashige and Skoog (MS) medium supplemented with 1 mg/L 2,4-D, 0.5 mg/L 6-benzyladenine (BA) and 0.5 mg/L kinetin (Kin). The highest shoot regeneration rate (57.14%) was obtained from hypocotyl-induced calli in MS medium with 0.5 mg/L Kin after 12 weeks of cultivation. This regeneration protocol can be used in large-scale cultivation and may be useful for future genetic modifications of
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http://dx.doi.org/10.1007/s11816-022-00772-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288091PMC
July 2022

Curcumin reduces inflammation in mice with the psoriasis model by inhibiting NLRP3 inflammatory bodies.

Cell Mol Biol (Noisy-le-grand) 2022 Feb 27;67(6):48-54. Epub 2022 Feb 27.

Department of Pharmacy, Hongze Huaian District People's Hospital, Huai'an, 223100, China.

As a chronic skin disease, psoriasis is a relatively common disease among various types of skin diseases. Because this disease is often distributed throughout the patient's body and is prone to develop, it is difficult to guarantee the quality of life and physical and mental health of patients with this disease. The purpose of this article is to investigate whether curcumin can effectively inhibit the NLRP3 inflammatory body and thereby reduce the inflammation in the mouse psoriasis model. Through the use of the curcumin gel prepared and the mouse psoriasis model, the percutaneous administration was used to investigate the mechanism and mechanism of curcumin's effect on reducing inflammation in the mouse psoriasis model. In addition, in order to better explore the curative effect of curcumin on psoriasis, related experiments were conducted by setting up a control group and an experimental group. The results show that curcumin has a good inhibitory effect on NLRP3 inflammatory bodies. Curcumin can not only reduce the NLRP3 expression and inhibit the inflammation caused by IL-22 and IL-18 but also reduce the damage of psoriasis. 22 Induced phosphorylation of STAT3 almost completely inhibits phosphorylation in normal cells. Among them, curcumin inhibited IL-22-induced phosphorylation of STAT3 up to 95.6%, and inhibited IL-22 and IL-18 by about 47%.
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http://dx.doi.org/10.14715/cmb/2021.67.6.7DOI Listing
February 2022

GTransU-CAP: Automatic labeling for cyclic alternating patterns in sleep EEG using gated transformer-based U-Net framework.

Comput Biol Med 2022 Aug 3;147:105804. Epub 2022 Jul 3.

School of Information Science and Technology, Fudan University, Shanghai, 200433, China; Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention (MICCAI) of Shanghai, Shanghai, 200032, China.

Cyclic alternating pattern (CAP) sequences are composed of cycles of alternate activation phases (A-phases) and background phases. CAP A-phases can be further divided into three subtypes, which act as important bio-markers of sleep instability and are also associated with identifiable sleep pathologies. Thus, its accurate detection and identification is of great clinical interest and significance. To release the burden of sleep experts who manually perform this labeling task, several automatic detectors have been proposed, yet the characteristics of CAP have not been fully exploited to achieve a satisfactory performance. In this paper, we propose an automated method to detect A-phases and their subtypes using Transformer-based U-Net framework. In light of the long-span duration of A-phases, our method has intrinsic advantages as U-Net extracts local information while Transformer module provides global dependencies. We also use a curriculum-learning based training strategy to further improve the performance. The method is validated on the publicly available CAP Sleep Database. It obtains average F1 scores of 67.78% and 72.16% on 16 healthy subjects and 30 patients with nocturnal frontal lobe epilepsy respectively for A-phase detection, and the average macro F1-score is 59.5% for multi-class subtype classification. Compared with state-of-the-art methods, the proposed method achieves superior performance in these two CAP labeling tasks.
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http://dx.doi.org/10.1016/j.compbiomed.2022.105804DOI Listing
August 2022

A national effort to improve outcomes for in-hospital cardiac arrest in China: The BASeline Investigation of Cardiac Arrest (BASIC-IHCA).

Resusc Plus 2022 Sep 23;11:100259. Epub 2022 Jun 23.

Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China; Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China.

Background: In-hospital cardiac arrest (IHCA) is a common clinical event with poor outcomes. Former IHCA registries in China were local, inconsistent in data reporting, and lacked attention to the process of care. Therefore, we designed and implemented the BASeline Investigation of In-hospital Cardiac Arrest (BASIC-IHCA), the first national IHCA registry in China.

Methods: BASIC-IHCA is a prospective, multicenter, observational study with a nationwide surveillance network covering urban and rural hospitals from seven geographic regions of China. IHCA patients were enrolled continuously, and data were collected from medical records by investigators at participating hospitals. Key variables referring to the updated Utstein Template included patient information, event variables, process of care, and outcomes. Follow-up was conducted by telephone interview to obtain details on long-term survival and neurological status.

Results: Thirty-two urban hospitals and eight rural hospitals from twenty-nine provinces in seven geographic regions of China participated in BASIC-IHCA. The starting time of enrollment ranged from July 1, 2019, to January 1, 2020. By December 31, 2020, 35,451 IHCAs were enrolled in all participating hospitals, of which 19,493 (55%) received CPR, with a predominance of males (65%) and a median age of 65 years.

Conclusion: BASIC-IHCA is the first national registry for IHCA in China. It will describe the epidemiology and outcomes of IHCA from a nationwide perspective, with a particular focus on details of the process of care for quality improvement. Meanwhile, it will help to facilitate the standardization of IHCA-related data reporting in China.
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http://dx.doi.org/10.1016/j.resplu.2022.100259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240856PMC
September 2022

Dietary olive oil enhances the oral tolerance of the food allergen ovalbumin in mice by regulating intestinal microecological homeostasis.

J Food Biochem 2022 Jul 2:e14297. Epub 2022 Jul 2.

College of Ocean Food and Biological Engineering, Xiamen Key Laboratory of Marine Functional Food, Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Jimei University, Xiamen, People's Republic of China.

Increasing evidence indicates that intestinal microecological imbalances are strongly associated with food allergen intolerance. This study investigated the effect of olive oil on food allergy susceptibility and intestinal microecology based on an ovalbumin (OVA)-sensitized mouse model. The results indicated that the allergic symptoms of sensitized mice were alleviated when they were supplemented with olive oil at 1-3 g/kg per day for 7 weeks. Intestinal epithelium observation showed repaired ileum villi and upregulated tight junction (TJ) protein expression. Furthermore, the levels of the cytokines (e.g., IL-10) secreted by regulatory T cells were increased, whereas T helper 2 (Th2) cell-associated factors were decreased in lamina propria. Furthermore, 16S rRNA sequencing indicated reduced Burkholderiaceae and increased Clostridiaceae in the intestinal microflora. The results suggest that an olive oil-enriched diet may effectively prevent food allergies by regulating the intestinal microecological balance. PRACTICAL APPLICATIONS: Recent studies emphasized that intestinal ecological imbalance, including intestinal immunity and microflora structure, plays an important role in affecting the occurrence and development of food allergy. The present results implied that olive oil, one of the main components of the Mediterranean diet, can effectively ameliorate the symptoms of OVA-induced food allergy by regulating intestinal microecological homeostasis. Therefore, dietary supplementation with olive oil may be an effective strategy for preventing food allergies.
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http://dx.doi.org/10.1111/jfbc.14297DOI Listing
July 2022

Ambient NO exposure induces migraine in rats: Evidence, mechanisms and interventions.

Sci Total Environ 2022 Jun 29:157102. Epub 2022 Jun 29.

Department of Health Toxicology, Xiangya School of Public Health, Central South University, Changsha 410078, PR China. Electronic address:

Migraine is a complex neurological disorder with a high disability rate. Although the precipitating factors of migraine remain unclear, previous studies suggest that when there is excess nitrogen dioxide (NO) pollution in the atmosphere, the medical demand due to migraine attacks increases sharply. However, the main role of NO as a trigger for migraine is not yet well understood. The purpose of this study was to explore the relationship between NO exposure and the occurrence of migraine as well as the possible underlying mechanisms. We first investigated whether repeated short-term NO exposure could induce behavioural and biological migraine phenotypes in rats. Next, capsazepine (CZP) was used to block transient receptor potential cation channel subfamily V member 1 (TRPV1) in vivo, and CZP and vitamin E (VE) were used to verify the role of reactive oxygen species (ROS)-TRPV1 signalling in NO-induced migraine in primary trigeminal neurones in vitro. We demonstrated that short-term repeated NO exposure can significantly induce migraine in rats, and its key molecular mechanism may be related to ROS burst and its downstream TRPV1 channel activation. The findings of this study will enhance the understanding of the neurotoxic mechanism of NO, provide new clues for identifying the aetiology of migraine, and lay a new experimental basis for implementing migraine-related preventive and therapeutic control measures.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157102DOI Listing
June 2022

Charged Nanochannels in Covalent Organic Framework Membranes Enabling Efficient Ion Exclusion.

ACS Nano 2022 Jun 30. Epub 2022 Jun 30.

Key Laboratory for Green Chemical Technology of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.

Controllable ion transport through nanochannels is crucial for biological and artificial membrane systems. Covalent organic frameworks (COFs) with regular and tunable nanochannels are emerging as an ideal material platform to develop synthetic membranes for ion transport. However, ion exclusion by COF membranes remains challenging because most COF materials have large-sized nanochannels leading to nonselective transport of small ions. Here we develop ionic COF membranes (iCOFMs) to control ion transport through charged framework nanochannels, the interior surfaces of which are covered with arrayed sulfonate groups to render superior charge density. The overlap of an electrical double layer in charged nanochannels blocks the entry of co-ions, narrows their passageways, and concomitantly restrains the permeation of counterions the charge balance. These highly charged large-sized nanochannels within the iCOFM enable ion exclusion while maintaining intrinsically high water permeability. Our results reveal possibilities for controllable ion transport based on COF membranes for water purification, ionic separation, sensing, and energy conversion.
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http://dx.doi.org/10.1021/acsnano.2c04767DOI Listing
June 2022

Microwave ablation vs. surgery for papillary thyroid carcinoma with minimal sonographic extrathyroid extension: a multicentre prospective study.

Eur Radiol 2022 Jun 30. Epub 2022 Jun 30.

Department of Interventional Ultrasound, Chinese PLA General Hospital, No.28 Fuxing Road, Haidian District, Beijing, 100853, China.

Objectives: Minimal extrathyroid extension (mETE) was removed from the TNM staging system. This study was designed prospectively to compare the safety and efficacy of microwave ablation (MWA) versus surgery for treating T1N0M0 papillary thyroid carcinomas (PTC) with sonographically detected mETE.

Methods: From December 2019 to April 2021, 198 patients with T1N0M0 mETE-PTCs evaluated by preoperative ultrasound from 10 hospitals were included. Ninety-two patients elected MWA, and 106 patients elected surgery for treatment. MWA was performed using extensive ablation with hydrodissection. Surgery consisted of lobectomy with ipsilateral central lymph node dissection (CLD), lobe and isthmus excision with ipsilateral CLD and total thyroidectomy with ipsilateral CLD. The rates of technical success, cost, oncologic outcomes, complications and quality of life of the two groups were assessed.

Results: The follow-up times for the MWA and surgery groups were 12.7 ± 4.1 and 12.6 ± 5.0 months, respectively. The technical success rate was 100% for both groups. Oncological outcomes of the two groups were similar during the follow-up (all p > 0.05). The MWA group had a shorter operation time, less blood loss and lower costs (all p < 0.001). Three complications (3.3%) were reported in the MWA group and 4 (3.8%) in the surgery group (p = 0.846). The surgery group had higher scores for scar problems and anxiety (p < 0.001 and p = 0.003, respectively).

Conclusions: Microwave ablation was comparable in the short term to surgery in terms of treatment safety and efficacy in selected patients with T1N0M0 mETE-PTC detected by ultrasound.

Key Points: • Microwave ablation is comparable to surgery in the safety and short-term efficacy for PTCs with sonographically detected mETE. • Thermal ablation is technically feasible for mETE-PTC treatment. • Patients with mETE-PTC have similar quality of life in the two groups, except for worse scar problems and anxiety in the surgery group.
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http://dx.doi.org/10.1007/s00330-022-08962-6DOI Listing
June 2022

High Expression of MUC5AC, MUC5B, and Layilin Plays an Essential Role in Prediction in the Development of Plastic Bronchitis Caused by MPP.

Front Microbiol 2022 13;13:911228. Epub 2022 Jun 13.

Department of Respiratory Medicine, Children's Hospital of Soochow University, Suzhou, China.

Plastic bronchitis (PB) is a rare respiratory condition which can result in severe respiratory complications such as respiratory failure and death. infection is a main etiology cause of plastic bronchitis. However, the pathogenesis of plastic bronchitis complicated by pneumonia (MPP) has not yet been fully elucidated. Our article aims to explore biomarkers for early prediction of MPP cases complicated with plastic bronchitis. We utilized a protein chip to screen for significantly different proteins among the groups of healthy, general pneumonia (GMPP) and refractory pneumonia (RMPP) patients, where layilin exhibited a potent change across biology information technology. Next, we demonstrated the high expression of MUC5AC, MUC5B, and layilin in bronchoalveolar lavage fluid (BALF) of MPP cases complicated with plastic bronchitis. Further study suggested that the level of layilin had a positive correlation with both MUC5AC and MUC5B. A receiver operating characteristic (ROC) analysis was performed to assess the diagnostic values of MUC5AC, MUC5B, and layilin in MPP cases with PB. Data show that the three indicators have similar diagnostic ability for MPP children with plastic bronchitis. Then, we used different concentrations of community-acquired respiratory distress syndrome (CARDS) toxin or lipid-associated membrane proteins (LAMPs) to simulate an experiment. The assay revealed that CARDS toxin or LAMPs induced A549 cells to secrete MUC5AC, MUC5B, layilin, and proinflammatory factors. These findings suggest that MUC5AC, MUC5B, and layilin are correlated with MPP. The high expression of MUC5AC, MUC5B, and layilin play an essential role in prediction in the development of plastic bronchitis caused by MPP. The high expression of MUC5AC, MUC5B, and layilin may be relevant to the severity of illness.
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http://dx.doi.org/10.3389/fmicb.2022.911228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234514PMC
June 2022

Loss of Heterozygosity for Promotes Malignant Phenotype of Pancreatic Ductal Adenocarcinoma by Activating HIF-2α-c-Myc-Regulated Glutamine Metabolism.

Int J Mol Sci 2022 Jun 15;23(12). Epub 2022 Jun 15.

Department of Pathology, Xuzhou Medical University, Xuzhou 221004, China.

Loss of heterozygosity (LOH) for , in which a wild-type allele is progressively lost, promotes invasive and migratory abilities of pancreatic ductal adenocarcinoma (PDAC) cells and tissues. Moreover, the occurrence of -LOH activates nonclassical glutamine metabolism, which is related to the malignant behavior of PDAC cells. Herein, we aim to demonstrate the regulatory link between hypoxia-inducible factor-2α (HIF-2α) and glutamine metabolism that mediates malignant phenotypes in -LOH PDAC cells. HIF-2α-shRNA knockdown lentivirus transfection and metabolite analysis were performed in -LOH and cell lines, respectively. Cell proliferation, migration, and invasion were examined using Cell Counting Kit-8, colony formation, and Transwell assays. Cell cycle phase and apoptosis were determined using flow cytometry. Western blotting and real-time quantitative PCR were also performed. Additionally, a subcutaneous xenograft mouse model was established. LOH stimulated HIF-2α activity and transactivated c-Myc, which has a central regulatory effect on glutamine metabolism independent of hypoxia. Meanwhile, HIF-2α silencing repressed -LOH PDAC cell proliferation, invasion, and migration. HIF-2α knockdown inhibited glutamine uptake and GOT1 expression via a c-Myc-dependent pathway. Collectively, -LOH can activate HIF-2α to regulate c-Myc-mediated glutamine metabolism and promote malignant phenotypes. Moreover, targeting HIF-2α-c-Myc regulated nonclassical glutamine metabolism, providing a new therapeutic perspective for -LOH PDAC.
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http://dx.doi.org/10.3390/ijms23126697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224498PMC
June 2022

The Effect of Propofol versus Sevoflurane on Postoperative Delirium in Parkinson's Disease Patients Undergoing Deep Brain Stimulation Surgery: An Observational Study.

Brain Sci 2022 May 25;12(6). Epub 2022 May 25.

Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.

Background: The selection of the maintenance of general anesthesia may affect the development of postoperative delirium (POD), notably for Parkinson's disease (PD) patients, due to their lower cognitive reserve. The present study was designed to compare the potential impact of propofol vs. sevoflurane based general anesthesia maintenance methods on the development of POD in PD patients following deep brain stimulation (DBS) surgery.

Methods: A total of 125 PD patients who were scheduled to undergo DBS surgery were randomly divided into the propofol ( = 63) and the sevoflurane groups ( = 62). The patients in the two groups randomly received propofol- or sevoflurane-based general anesthesia. The Confusion Assessment Method (CAM) was employed by an investigator who was blinded to the anesthesia regimen and was administered twice per day from postoperative day 1 until discharge.

Results: The incidence of POD was 22.22% (14/63) with propofol anesthesia and 20.97% (13/62) with sevoflurane anesthesia ( 0.865). In addition, no difference was noted in the duration and severity of delirium between the propofol and sevoflurane groups.

Conclusions: In the present study, propofol- and sevoflurane-based general anesthesia exhibited comparable results with regard to the POD incidence in PD patients undergoing deep brain stimulation surgery.
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http://dx.doi.org/10.3390/brainsci12060689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221052PMC
May 2022

Functional differentiation of three pheromone binding proteins in Orthaga achatina using mixed-type sex pheromones.

Pestic Biochem Physiol 2022 Jun 12;184:105097. Epub 2022 Apr 12.

Key Laboratory of Integrated Management of Crop Disease and Pests, Ministry of Education/Department of Entomology, College of Plant Protection, Nanjing Agricultural University, 210095 Nanjing, China. Electronic address:

Pheromone-binding proteins (PBPs) play important roles in perception of insect sex pheromones, functioning to recognize and transport pheromone components onto the olfactory receptors of the odorant sensing neurons. Orthaga achatina, a serious pest of camphor trees, uses a mixture of three Type I (Z11-16:OAc, Z11-16:OH and Z11-16:Ald) and one Type II (Z3,Z6,Z9,Z12,Z15-23:H) sex pheromone components in its sex communication, in which Z11-16:OAc is the major component and others are minor components. In this study, we for the first time demonstrated that the three PBPs differentiated in recognition among pheromone components in a moth using mixed-type sex pheromones. First, tissue expression study showed that all three PBPs of O. achatina were expressed only in antennae and highly male-biased, suggesting their involvement in perception of the sex pheromones. Second, the three PBPs were expressed in Escherichia coli and the binding affinities of PBPs to four sex pheromone components and some pheromone analogs were determined by the fluorescence competition binding assays. The results showed that OachPBP1 bound all four sex pheromone components with high binding affinity, while OachPBP2 had high or moderate binding affinity only to three Type I components, and OachPBP3 had high binding affinity only to three minor pheromone components. Furthermore, key amino acid residues that bind to sex pheromone components were identified in three PBPs by 3-D structure modeling and ligand molecular docking, predicting the interactions between PBPs and pheromone components. Our study provides a fundamental insight into the olfactory mechanism in moths that use mixed-type sex pheromones.
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http://dx.doi.org/10.1016/j.pestbp.2022.105097DOI Listing
June 2022

[Detection of NPM1 Mutation in Acute Myeloid Leukemia by Droplet Digital PCR and Its Clinical Application Value].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2022 Jun;30(3):653-658

Department of Hematology, The Affiliated People's Hospital of Jiangsu University,Zhenjiang 212002, Jiangsu Province, China;Zhenjiang Clinical Research Center of Hematology,Zhenjiang 212002, Jiangsu Province, China,Email:

Objective: To establish the droplet digital PCR (ddPCR) assay for the detection of NPM1 type A mutation in patients with acute myeloid leukemia (AML), and to evaluate its specificity, sensitivity and its value in clinical application.

Methods: NPM1 mutant and wildtype plasmids were used to verify the performance of ddPCR. Both ddPCR and Sanger sequencing were used to detect the bone marrow samples of 87 AML patients, which were confirmed by next generation sequencing (NGS). Moreover, NPM1 mutation burden was dynamically monitored in five patients by ddPCR.

Results: The limit of blank (LOB) of ddPCR established for NPM1 mutation detection was 1.1 copies/μl, and the limit of detection (LOD) was 2.43 copies/μl, which had good linearity. Among the 87 newly diagnosed AML patients, ddPCR identified seventeen cases positive for NPM1 mutation (19.5%), which was consistent with Sanger sequencing. NGS confirmed 12 positive cases, including 8 of type A mutations, 2 of type D mutations, and 2 of rare type mutations. The results of dynamic monitoring of NPM1 mutation burden in 5 patients showed that the NPM1 mutation burden decreased obviously even close to 0, when patients achieve complete remission after chemotherapy. However, the mutation burden was increased again at the time of relapse.

Conclusion: In this study, we established a ddPCR method for detection of NPM1 mutation with good sensitivity and repeatability, which can be used for screening NPM1 mutation in newly diagnosed AML patients and for minimal residual disease monitoring after remission in positive AML patients to guide treatment.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2022.03.001DOI Listing
June 2022

STAT6 inhibits ferroptosis and alleviates acute lung injury via regulating P53/SLC7A11 pathway.

Cell Death Dis 2022 Jun 6;13(6):530. Epub 2022 Jun 6.

Chongqing University Central Hospital&Chongqing Emergency Medical Center, No.1 Jiankang Road, Yuzhong District, Chongqing, 400014, China.

Compelling evidences have revealed the emerging role of ferroptosis in the pathophysiological process of acute lung injury (ALI), but its modulation is not clear. Here, we identified that STAT6 acted as a critical regulator of epithelium ferroptosis during ALI. Firstly, STAT6 expression and activity were increased in the ALI mice models caused by crystalline silica (CS), LPS and X-ray exposure. Followed by confirming the contribution of ferroptosis in the above ALI with ferrostatin-1 and deferoxamine intervention, bioinformatic analyses revealed that STAT6 expression was negatively correlated with ferroptosis. Consistently, lung epithelium-specific depletion of STAT6 in mice or STAT6 knockdown in cultured epithelial cells exacerbated ferroptosis in the above ALI. While overexpression of STAT6 in lung epithelial cells attenuated the ferroptosis. Mechanistically, SLC7A11 is a typical ferroptosis-related gene and negatively regulated by P53. CREB-binding protein (CBP) is a critical acetyltransferase of P53 acetylation, showing valuable regulation on targets' transcription. Herein, we found that STAT6 negatively regulates ferroptosis through competitively binding with CBP, which inhibits P53 acetylation and transcriptionally restores SLC7A11 expression. Finally, pulmonary-specific STAT6 overexpression decreased the ferroptosis and attenuated CS and LPS induced lung injury. Our findings revealed that STAT6 is a pivotal regulator of ferroptosis, which may be a potential therapeutic target for the treatment of acute lung injury.
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http://dx.doi.org/10.1038/s41419-022-04971-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9169029PMC
June 2022

Concurrent Structural and Functional Patterns in Patients With Amnestic Mild Cognitive Impairment.

Front Aging Neurosci 2022 17;14:838161. Epub 2022 May 17.

Department of Geriatric Psychiatry, Suzhou Mental Health Center, Suzhou Guangji Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, China.

Amnestic mild cognitive impairment (aMCI) is a clinical subtype of MCI, which is known to have a high risk of developing Alzheimer's disease (AD). Although neuroimaging studies have reported brain abnormalities in patients with aMCI, concurrent structural and functional patterns in patients with aMCI were still unclear. In this study, we combined voxel-based morphometry (VBM), amplitude of low-frequency fluctuations (ALFFs), regional homogeneity (Reho), and resting-state functional connectivity (RSFC) approaches to explore concurrent structural and functional alterations in patients with aMCI. We found that, compared with healthy controls (HCs), both ALFF and Reho were decreased in the right superior frontal gyrus (SFG_R) and right middle frontal gyrus (MFG_R) of patients with aMCI, and both gray matter volume (GMV) and Reho were decreased in the left inferior frontal gyrus (IFG_L) of patients with aMCI. Furthermore, we took these overlapping clusters from VBM, ALFF, and Reho analyses as seed regions to analyze RSFC. We found that, compared with HCs, patients with aMCI had decreased RSFC between SFG_R and the right temporal lobe (subgyral) (TL_R), the MFG_R seed and left superior temporal gyrus (STG_L), left inferior parietal lobule (IPL_L), and right anterior cingulate cortex (ACC_R), the IFG_L seed and left precentral gyrus (PRG_L), left cingulate gyrus (CG_L), and IPL_L. These findings highlighted shared imaging features in structural and functional magnetic resonance imaging (MRI), suggesting that SFG_R, MFG_R, and IFG_L may play a major role in the pathophysiology of aMCI, which might be useful to better understand the underlying neural mechanisms of aMCI and AD.
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http://dx.doi.org/10.3389/fnagi.2022.838161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161636PMC
May 2022

Phenotypic and Genetic Characterization of the Lentil Single Plant-Derived Core Collection for Resistance to Root Rot Caused by .

Phytopathology 2022 Aug 3:PHYTO12210517R. Epub 2022 Aug 3.

USDA-ARS Grain Legume Genetics and Physiology Research Unit, Prosser, WA 99350.

Lentil () is a pulse crop grown for its amino acid profile, moderate drought tolerance, and ability to fix nitrogen. As the global demand for lentils expands and new production regions emerge so too have the complement of diseases that reduce yield, including the root rot complex. Although the predominant causal pathogen varies based on growing region, is often found to be an important contributor to disease. This study screened part of the lentil single plant-derived core collection for resistance to in a greenhouse. Plants were phenotyped for disease severity using three scoring scales and the differences in biomass traits due to pathogen presence were measured. Lentil accessions varied in disease severity and differences in biomass traits were found to be correlated with each visual severity estimate ( = -0.37 to -0.63, < 0.001), however, heritability estimates were low to moderate among traits ( = 0.12 to 0.43). Results of a genome-wide association study (GWAS) using single nucleotide polymorphism (SNP) markers derived from genotyping-by-sequencing revealed 11 quantitative trait loci (QTL) across four chromosomes. Two pairs of QTL colocated for two traits and were found near putative orthologs that have been previously associated with plant disease resistance. The identification of lentil accessions that did not exhibit a difference in biomass traits may serve as parental material in breeding or in the development of biparental mapping populations to further validate and dissect the genetic control of resistance to root rot caused by .
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http://dx.doi.org/10.1094/PHYTO-12-21-0517-RDOI Listing
August 2022

Using Artificial Intelligence to Find the Optimal Margin Width in Hepatectomy for Colorectal Cancer Liver Metastases.

JAMA Surg 2022 Aug 10;157(8):e221819. Epub 2022 Aug 10.

Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Importance: In patients with resectable colorectal cancer liver metastases (CRLM), the choice of surgical technique and resection margin are the only variables that are under the surgeon's direct control and may influence oncologic outcomes. There is currently no consensus on the optimal margin width.

Objective: To determine the optimal margin width in CRLM by using artificial intelligence-based techniques developed by the Massachusetts Institute of Technology and to assess whether optimal margin width should be individualized based on patient characteristics.

Design, Setting, And Participants: The internal cohort of the study included patients who underwent curative-intent surgery for KRAS-variant CRLM between January 1, 2000, and December 31, 2017, at Johns Hopkins Hospital, Baltimore, Maryland, Memorial Sloan Kettering Cancer Center, New York, New York, and Charité-University of Berlin, Berlin, Germany. Patients from institutions in France, Norway, the US, Austria, Argentina, and Japan were retrospectively identified from institutional databases and formed the external cohort of the study. Data were analyzed from April 15, 2019, to November 11, 2021.

Exposures: Hepatectomy.

Main Outcomes And Measures: Patients with KRAS-variant CRLM who underwent surgery between 2000 and 2017 at 3 tertiary centers formed the internal cohort (training and testing). In the training cohort, an artificial intelligence-based technique called optimal policy trees (OPTs) was used by building on random forest (RF) predictive models to infer the margin width associated with the maximal decrease in death probability for a given patient (ie, optimal margin width). The RF component was validated by calculating its area under the curve (AUC) in the testing cohort, whereas the OPT component was validated by a game theory-based approach called Shapley additive explanations (SHAP). Patients from international institutions formed an external validation cohort, and a new RF model was trained to externally validate the OPT-based optimal margin values.

Results: This cohort study included a total of 1843 patients (internal cohort, 965; external cohort, 878). The internal cohort included 386 patients (median [IQR] age, 58.3 [49.0-68.7] years; 200 men [51.8%]) with KRAS-variant tumors. The AUC of the RF counterfactual model was 0.76 in both the internal training and testing cohorts, which is the highest ever reported. The recommended optimal margin widths for patient subgroups A, B, C, and D were 6, 7, 12, and 7 mm, respectively. The SHAP analysis largely confirmed this by suggesting 6 to 7 mm for subgroup A, 7 mm for subgroup B, 7 to 8 mm for subgroup C, and 7 mm for subgroup D. The external cohort included 375 patients (median [IQR] age, 61.0 [53.0-70.0] years; 218 men [58.1%]) with KRAS-variant tumors. The new RF model had an AUC of 0.78, which allowed for a reliable external validation of the OPT-based optimal margin. The external validation was successful as it confirmed the association of the optimal margin width of 7 mm with a considerable prolongation of survival in the external cohort.

Conclusions And Relevance: This cohort study used artificial intelligence-based methodologies to provide a possible resolution to the long-standing debate on optimal margin width in CRLM.
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http://dx.doi.org/10.1001/jamasurg.2022.1819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161118PMC
August 2022

Construction of Severe Eosinophilic Asthma Related Competing Endogenous RNA Network by Weighted Gene Co-Expression Network Analysis.

Front Pharmacol 2022 11;13:852536. Epub 2022 May 11.

School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China.

Currently, disease control in patients with severe eosinophilic asthma is not optimistic. Competing endogenous RNA (ceRNA) networks have been found to play a key role in asthma in recent years. However, it is unclear whether ceRNA networks play an important part in severe eosinophilic asthma. Firstly, gene expression profiles related to severe eosinophilic asthma were downloaded from the Gene Expression Omnibus (GEO) database. Secondly, the key modules were identified by the weighted gene co-expression network analysis (WGCNA). Thirdly, genes in modules highly associated with severe eosinophilic asthma were selected for further construction of the ceRNA network. Fourthly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on hub genes. Finally, the results of this study were validated on the GSE143303, GSE137268, and GSE147878 datasets. 22 severe eosinophilic asthmatics and 13 healthy controls were extracted for WGCNA. We found that the genes in the black module ( = -0.75, < 0.05) and yellow module ( = 0.65, < 0.05) were highly associated with severe eosinophilic asthma. EP300 was discovered to serve the key connecting function in the ceRNA network. Surprisingly, lncRNAs seem to eliminate the role of EP300 in the black module and we discovered that CCT8 and miRNA-mRNA formed a circRNA-miRNA-mRNA network in the yellow module. We found that EP300 and FOXO3 in the black module were regulated by steroid hormones in the enrichment analysis, which were related to the medication used by the patient. Through validation of other datasets, we found that the hub genes in the yellow module were the key genes in the treatment of severe eosinophilic asthma. In particular, RPL17 and HNRNPK might specifically regulate severe eosinophilic asthma. RPL17 and HNRNPK might particularly regulate severe eosinophilic asthma. Our results could be useful to provide potential immunotherapy targets and prognostic markers for severe eosinophilic asthma.
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http://dx.doi.org/10.3389/fphar.2022.852536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130708PMC
May 2022
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