Publications by authors named "Yong Jiang"

1,339 Publications

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EXPRESS: Characteristics and Prognosis of Patients with Embolic Stroke of Undetermined Source in China.

Int J Stroke 2021 Jun 14:17474930211028040. Epub 2021 Jun 14.

Beijing Tiantan Hospital, Beijing, China.

Background And Purpose: We aimed to explore the frequencies, risk factors, and natural history of ESUS through a national prospective registry in China.

Methods: Between August 2015 and March 2018, the Third China National Stroke Registry (CNSR-III) recruited consecutive patients with ischemic stroke or transient ischemic attack (TIA) in China. The baseline characteristics, risks of stroke, and mortality in patients with ESUS were described and compared with that in patients with other causative subtypes.

Results: A total of 15166 TIA and ischemic stroke patients were enrolled in CNSR-III. Among 8528 ischemic stroke with standard diagnostic work-up, 2415 (28.3%) patients were diagnosed with ESUS. The mean age was 61 years and 70% of them were male. Compared to patients with cardioembolic strokes and small vessel disease, patients with ESUS had higher prevalence of nonstenosing large artery atherosclerosis (37.93% vs 31.26%, P=0.008 and 37.93% vs 34.40%, P=0.044 respectively). The cumulative probability of stroke recurrence in patients with ESUS at 3 month and 1 year was 5.59% and 8.74%. Compared with ESUS patients (0.70% and 1.99%), patients with the large artery atherosclerosis and cardioembolic strokes had higher cumulative probability of death at 3 month (1.94% and 3.22%) and 1 year (4.17% and 7.39%).

Conclusions: ESUS is a common cause of ischemic stroke in Chinese population with a higher stroke recurrence of ESUS than previous reported. It was more likely to have nonstenosing large artery atherosclerosis in patients with ESUS than with cardioembolic strokes and small vessel disease.
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http://dx.doi.org/10.1177/17474930211028040DOI Listing
June 2021

Effects of Seaweed Extracts on the Growth, Physiological Activity, Cane Yield and Sucrose Content of Sugarcane in China.

Front Plant Sci 2021 26;12:659130. Epub 2021 May 26.

College of Natural Resources and Environment, South China Agricultural University, Guangzhou, China.

Seaweed extracts (SEs) have been widely used as biostimulants in crop management due to their growth-promoting and stress-resistant effects. To date, there are few reports of the effect of SEs on sucrose content and cane yield. Here, we conducted field experiments for three consecutive growth seasons (2017∼2019) in two areas (Suixi and Wengyuan) of China, to investigate the yield and sugar content of sugarcane in response to SE treatment at different growth stages. The results showed that spraying SEs once at seedling (S), early elongation (E), and early mature (M) stages, respectively, once at S and E stages, respectively, or once at the S stage increased the cane yield by 9.23, 9.01, and 3.33%, respectively, implying that SEs application at the early elongation stage played a vital role in promoting sugarcane growth. Photosynthetic parameters and nutrient efficiency analysis showed that spraying SEs at S and E stages enhanced the net photosynthetic rate, transpiration rate, and water use efficiency, and increased N, P, or K utilization efficiency, compared with those of the control. Notably, cane yield increasing rate of SEs in 2017 and 2018 were higher than those in 2019 in Wengyuan but lower than those in 2019 in Suixi. Interestingly, the total rainfall and monthly average rainfall in 2017 and 2018 were lower than those in 2019 in Wengyuan but higher than those in 2019 in Suixi. The results suggested that the yield increasing rate of SEs on sugarcane was better in less rainfall years. The sucrose content of sugarcane showed no difference between spraying SEs at the M stage alone or at the three growth stages but was higher than those of SE treatments at S and/or E stages. Enzyme activity analysis showed that spraying SEs at the M stage increased the activity of sucrose phosphate synthase activity by 9.14% in leaves and 15.16% in stems, and decreased soluble acid invertase activity in stems by 16.52%, which contributed to the sucrose increase of 5.00%. The above results suggested that SEs could increase cane yield and promote sucrose accumulation in sugarcane. The yield increasing effect was more obvious under conditions of drought stress.
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http://dx.doi.org/10.3389/fpls.2021.659130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189154PMC
May 2021

Unlocking big data doubled the accuracy in predicting the grain yield in hybrid wheat.

Sci Adv 2021 Jun 11;7(24). Epub 2021 Jun 11.

Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), 06466 Stadt Seeland, Germany.

The potential of big data to support businesses has been demonstrated in financial services, manufacturing, and telecommunications. Here, we report on efforts to enter a new data era in plant breeding by collecting genomic and phenotypic information from 12,858 wheat genotypes representing 6575 single-cross hybrids and 6283 inbred lines that were evaluated in six experimental series for yield in field trials encompassing ~125,000 plots. Integrating data resulted in twofold higher prediction ability compared with cases in which hybrid performance was predicted across individual experimental series. Our results suggest that combining data across breeding programs is a particularly appropriate strategy to exploit the potential of big data for predictive plant breeding. This paradigm shift can contribute to increasing yield and resilience, which is needed to feed the growing world population.
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http://dx.doi.org/10.1126/sciadv.abf9106DOI Listing
June 2021

ggtreeExtra: Compact visualization of richly annotated phylogenetic data.

Mol Biol Evol 2021 Jun 7. Epub 2021 Jun 7.

Department of Bioinformatics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.

We present the ggtreeExtra package for visualizing heterogeneous data with a phylogenetic tree in a circular or rectangular layout (https://www.bioconductor.org/packages/ggtreeExtra). The package supports more data types and visualization methods than other tools. It supports using the grammar of graphics syntax to present data on a tree with richly annotated layers and allows evolutionary statistics inferred by commonly used software to be integrated and visualized with external data. GgtreeExtra is a universal tool for tree data visualization. It extends the applications of the phylogenetic tree in different disciplines by making more domain-specific data to be available to visualize and interpret in the evolutionary context.
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http://dx.doi.org/10.1093/molbev/msab166DOI Listing
June 2021

Diversity and co-occurrence networks of picoeukaryotes as a tool for indicating underlying environmental heterogeneity in the Western Pacific Ocean.

Mar Environ Res 2021 Jun 1;170:105376. Epub 2021 Jun 1.

Key Laboratory of Physical Oceanography, Ministry of Education, Ocean University of China, Qingdao, 266100, China. Electronic address:

Picoeukaryotes are an essential component of microbial communities and play key roles in marine ecosystems. In this study, surface water picoeukaryotes were investigated at 32 stations along a latitudinal cross-section of the Western Pacific (WP) in 2015. Multivariate analyses demonstrated that there were clear spatial patterns in picoeukaryotic community structures which were consistent with the distributions of environmental variables. The spatial patterns of community structures and diversity indices were all significantly correlated with multiple environmental parameters, especially nutrients. Co-occurrence networks linked community variability to environmental heterogeneity. In summary, the construction of picoeukaryotic communities in the WP was significantly affected by numerous environmental variables, and certain variables were revealed as key forcing factors responsible for the main similarities between picoeukaryotic communities. This study details the relationships between the picoeukaryotes and environmental parameters in the WP, and provides insight for application of using picoeukaryotes as indicator in future bioassessment for open waters.
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http://dx.doi.org/10.1016/j.marenvres.2021.105376DOI Listing
June 2021

Identification of Potential Pathogenic Super-Enhancers-Driven Genes in Pulmonary Fibrosis.

Front Genet 2021 12;12:644143. Epub 2021 May 12.

Traditional Chinese Medicine Innovation Research Center, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China.

Abnormal fibroblast differentiation into myofibroblast is a crucial pathological mechanism of pulmonary fibrosis (PF). Super-enhancers, a newly discovered cluster of regulatory elements, are regarded as the regulators of cell identity. We speculate that abnormal activation of super-enhancers must be involved in the pathological process of PF. This study aims to identify potential pathogenic super-enhancer-driven genes in PF. Differentially expressed genes (DEGs) in PF mouse lungs were identified from a GEO dataset (GDS1492). We collected super-enhancers and their associated genes in human lung fibroblasts and mouse embryonic fibroblasts from SEA version 3.0, a network database that provides comprehensive information on super-enhancers. We crosslinked upregulated DEGs and super-enhancer-associated genes in fibroblasts to predict potential super-enhancer-driven pathogenic genes in PF. A total of 25 genes formed an overlap, and the protein-protein interaction network of these genes was constructed by the STRING database. An interaction network of transcription factors (TFs), super-enhancers, and associated genes was constructed using the Cytoscape software. Gene enrichment analyses, including KEGG pathway and GO analysis, were performed for these genes. Latent transforming growth factor beta (TGF-β) binding protein 2 (LTBP2), one of the predicted super-enhancer-driven pathogenic genes, was used to verify the predicted network's accuracy. LTBP2 was upregulated in the lungs of the bleomycin-induced PF mouse model and TGF-β1-stimulated mouse and human fibroblasts. Myc is one of the TFs binding to the LTBP2 super-enhancer. Knockout of super-enhancer sequences with a CRISPR/Cas9 plasmid or inhibition of Myc all decreased TGF-β1-induced LTBP2 expression in NIH/3 T3 cells. Identifying and interfering super-enhancers might be a new way to explore possible therapeutic methods for PF.
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http://dx.doi.org/10.3389/fgene.2021.644143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153712PMC
May 2021

Comparative pharmacokinetics study of six effective components between two dosage forms of Qixue-Shuangbu Prescription in rats by UPLC-MS/MS.

Biomed Chromatogr 2021 May 26:e5179. Epub 2021 May 26.

Department of Technology, Taizhou Hospital Affiliated to Nanjing University of Chinese Medicine, Taizhou, China.

Qixue-Shuangbu Prescription (QSP) is an efficacious prescription for treating heart failure, myocardial ischemia and other diseases. It is composed of nine Chinese herbs. This study investigated and compared the pharmacokinetics of QSP in rats by UPLC-MS/MS between two dosage forms of traditional decoction (TD) and compound tincture (CT). Owing to the complexity of the chemicals in QSP, ginsenoside Rg1, ginsenoside Re, ferulic acid, astragaloside IV, rhein and calycosin were chosen for the pharmacokinetics study. The method established for detecting serum specimens was shown to have acceptable selectivity, linearity, lower limit of quantitation, precision, accuracy, recovery, matrix effect and stability. The peak concentration, AUC and AUC of ginsenoside Re, ginsenoside Rg1, ferulic acid and rhein were significantly increased after oral administration of CT (P < 0.05), the half-life of ferulic acid in the CT group was lower than that in the TD group (P < 0.05) and the half-life and AUC of astragaloside IV in the CT group were significantly increased (P < 0.05), which revealed that wine-processing could influence the bioavailability and the elimination of these compounds. For better clinical efficacy, we suggest that the CT dosage form of QSP should be selected.
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http://dx.doi.org/10.1002/bmc.5179DOI Listing
May 2021

Autophagy inhibition enhances anti-pituitary adenoma effect of tetrandrine.

Phytother Res 2021 May 26. Epub 2021 May 26.

Laboratory of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, China.

Pituitary adenoma (PA) is a benign intracranial neoplasm originated from pituitary gland. Surgery is the first-line therapy for most of PAs, but lead to unsatisfactory prognosis in some cases. Tetrandrine (Tet) has anticancer effect on some cancers. However, growth inhibition effect on PA is unknown. To elucidate the inhibitory effect of Tet on the growth of PA and its potential mechanisms, we validated the in vitro and in vivo anti-PA effect of Tet and illustrated the cellular and molecular alterations by confocal microscopy observation, flow cytometry, and RNA interference. Tet inhibited PA cell growth in vitro and tumor progression in vivo. Tet induced autophagy and apoptosis in a dose-dependent manner. Low dosage (1.25 μM) of Tet induced PA cell autophagy by down-regulation of MAPK/STAT3 signal. While, higher dosage (5.0 μM) of Tet partially induced PA cell death through caspase-dependent apoptosis. Autophagy inhibitors enhanced Tet-induced caspase activity and apoptotic cell death. These findings demonstrated that Tet has anti-PA effect by inducing autophagy and apoptosis through MAPK/STAT3 signaling pathway attenuation and autophagy inhibition might enhance its anti-PA effect, indicating that Tet (or combined with autophagy inhibitor) is a potential therapeutic regimen for PAs.
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http://dx.doi.org/10.1002/ptr.7117DOI Listing
May 2021

FDI, economic growth, and carbon emissions of the Chinese steel industry: new evidence from a 3SLS model.

Environ Sci Pollut Res Int 2021 May 20. Epub 2021 May 20.

Research Institute of Digital Society and Blockchain, Hunan University, Changsha, 410082, China.

Determine the main factors affecting carbon emissions of the Chinese steel industry is indispensable commitments to achieve the sustainable development of China. Hereby, based on the Stochastic Impacts by Regression on Population, Affluence and Technology (STIPRAT) model, this paper combines the economic growth function, carbon emission production function, and the FDI function of the Chinese steel industry, and uses the three-stage least square equation model (3SLS) to analyze the relationship between China's economic growth, carbon emissions in the steel industry, and FDI (foreign direct investment) inflows. The results document a complete two-way causal relationship of three variables in the whole country and the Western region, while the relationship in the Eastern region and the Central region is not complete. Moreover, there are no bidirectional causal relationship between carbon emissions and FDI in the Eastern region, while only bidirectional causality between carbon emissions and FDI in the Central region. These findings are of great significance for the Chinese steel industry to formulate effective emission reduction policies.
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http://dx.doi.org/10.1007/s11356-021-14445-wDOI Listing
May 2021

Evaluation of the effects of notoginseng total saponins (NS), safflower total flavonoids (SF), and the combination of NS and SF (CNS) on the activities of cytochrome P450 enzymes using a cocktail method in rats.

Biomed Chromatogr 2021 May 19:e5171. Epub 2021 May 19.

School of Pharmaceutical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China.

Notoginseng total saponins (NS), safflower total flavonoids (SF), and the combination of NS and SF, namely CNS, are used for the treatment of cardiovascular diseases in clinic. This study developed a cocktail assay involving seven cytochrome P450 (CYP) enzymes to elucidate the effect of NS, SF, and CNS on CYP enzymes and to explore the synergistic effect of CNS in terms of CYP enzymes. Ultra-performance liquid chromatography-MS and reverse-transcription polymerase chain reaction were applied to detect the activities and mRNA expression levels of CYP enzymes. SF exhibited inhibitory effects on CYP1A2, 2B1, 2E1, and 2C11 and induction effects on CYP2C19 and 2D4. NS exhibited induction effects on CYP1A2, 2B1, 2E1, 2C11, 2C19, and 2D4. CNS exhibited induction effects on CYP1A2, 2B1, 2E1, 2C19, and 2D4 and inhibitory effects on CYP3A1 in vivo. Moreover, mRNA expression results were consistent with pharmacokinetic results. Potential herb-drug interactions should be studied closely when SF, NS, or CNS with clinical drugs are metabolized by CYP1A2, 2B1, 2E1, 2C11, 2C19, 2D4, and 3A1. CNS could change the inhibition or induction effects of CYP compared to the NS group, which might be one of the causes for the synergistic effects of the combination of NS and SF.
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http://dx.doi.org/10.1002/bmc.5171DOI Listing
May 2021

Dopants and grain boundary effects in monolayer MoS: a first-principles study.

Phys Chem Chem Phys 2021 May;23(20):11937-11943

Key Laboratory for Nonferrous Metal Materials Science and Engineering (MOE), School of Materials Science and Engineering, Central South University, Changsha, 410083, China.

The structural, electronic and magnetic properties of large area chemical vapor deposited monolayer MoS2 rely significantly on the presence of grain boundaries (GBs) and defects. In this study, first-principles calculations were performed to investigate the electronic and magnetic properties of transition metal doped MoS2 GBs. The experimentally observed 60° tilt GBs were demonstrated with four different atomic configurations and the nonmagnetic 4|8ud GB has the lowest formation energy among the considered models. Further calculations of 4|8ud GBs doped with TMs, such as V, Cr, Mn, Fe, Co and Ni, indicate that dopants can significantly lower the formation energies of the doped GBs compared to the perfect monolayer MoS2 by occupying the GB region instead of within the grains. Magnetism can be achieved in doped GB systems by careful defect engineering. CoMo, MnMo and Niint in 4|8ud GBs are predicted to be magnetic and simultaneously energetically favorable. The electron coupling between the doped TM and surrounding GB atoms is expected to induce magnetism and high electron mobilities into the systems. This study may pave the way for optimal design of MoS2-based electronic and spintronic devices.
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http://dx.doi.org/10.1039/d1cp00156fDOI Listing
May 2021

A Nomogram Based on Clinical and Ultrasound Characteristics to Predict Central Lymph Node Metastasis of Papillary Thyroid Carcinoma.

Front Endocrinol (Lausanne) 2021 28;12:666315. Epub 2021 Apr 28.

Department of Thyroid Surgery, The Third Affiliated Hospital of Soochow University, Changzhou First People's Hospital, Changzhou, China.

Background: The status of lymph nodes in the central compartment is crucial to determining the surgical strategies for papillary thyroid carcinoma (PTC). We aimed to develop a nomogram for predicting central lymph node metastasis (CLNM).

Methods: A total of 886 PTC patients who underwent total thyroidectomy or lobectomy with central neck dissection (CND) from July 2019 to June 2020 were retrospectively retrieved. Clinical and ultrasound features were collected. Univariate and multivariate analysis were performed to determine risk factors of CLNM. A nomogram for predicting CLNM was developed, internal and external calibration was performed for the established model.

Results: Variables (sex, chronic lymphocytic thyroiditis, tumor size, the number of foci, tumor location, margin) significantly associated with CLNM were included in the nomogram. The nomogram showed excellent calibration in the training group and validation group, with area under curves of 0.806 (95% CI, 0.771 to 0.825), and 0.799 (95% CI, 0.778-0.813) respectively.

Conclusion: Through this accurate and easy-to-use nomogram, the possibility of CLNM can be objectively quantified preoperatively. Clinicians can use this nomogram to evaluate the status of lymph nodes in PTC patients and consider prophylactic CND for those with high scores.
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http://dx.doi.org/10.3389/fendo.2021.666315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115120PMC
April 2021

Prototype Design of a Domain-Wall-Based Magnetic Memory Using a Single Layer LaSrMnO Thin Film.

ACS Appl Mater Interfaces 2021 May 11;13(20):23945-23950. Epub 2021 May 11.

Department of Physics, Beijing Normal University, Beijing, China.

Magnetic field-free, nonvolatile magnetic memory with low power consumption is highly desired in information technology. In this work, we report a current-controllable alignment of magnetic domain walls in a single layer LaSrMnO thin film with the threshold current density of 2 × 10 A/cm at room temperature. The vector relationship between current directions and domain-wall orientations indicates the dominant role of spin-orbit torque without an assistance of external magnetic field. Meanwhile, significant planar Hall resistances can be readout in a nonvolatile way before and after the domain-wall reorientation. A domain-wall-based magnetic random-access memory (DW-MRAM) prototype device has been proposed.
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http://dx.doi.org/10.1021/acsami.1c04724DOI Listing
May 2021

Potential Synergy Mechanism of Processing Methods for the Basic Remedies of Qixue Shuangbu Prescription Based on Integrated Metabolomics Strategy and Network Pharmacology Study.

J Chromatogr Sci 2021 May 10. Epub 2021 May 10.

Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, PR China.

Qixue Shuangbu Prescription (QSP) is a famous traditional Chinese medicine (TCM) formula widely used for the treatment of chronic heart failure (CHF). Previous clinical studies have found that the efficacy of processed QSP has been significantly enhanced in the treatment of CHF. However, the synergistic mechanisms of processed QSP to enhance the treatment of CHF are still unclear. Generally, the changes in clinical effects mainly result from the variations of inside chemical basis caused by the TCM processing procedure. In this study, we developed a network pharmacology-integrated metabolomics strategy to clarify the difference of the effective compounds between crude and processed QSP, and further explain the mechanism of processed QSP to produce a synergistic effects. As a result, 69 different compounds were successfully screened, identified, quantified and verified as the most potential marker compounds. These different chemical components may play an anti-CHF and enhance the therapeutic effect through 52 action pathways such as estrogen signaling pathway, ubiquitin mediated proteolysis, protein processing in endoplasmic reticulum, etc. This study revealed that the proposed network pharmacology-integrated metabolomics strategy was a powerful tool for explaining the mechanism of synergistic action in the processing of QSP, further controlling the quality and understanding the processing mechanism of TCM formulae.
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http://dx.doi.org/10.1093/chromsci/bmab053DOI Listing
May 2021

Influence of Early Enteral Nutrition on Clinical Outcomes in Neurocritical Care Patients With Intracerebral Hemorrhage.

Front Neurol 2021 20;12:665791. Epub 2021 Apr 20.

Department of Neurology, University Hospital Erlangen-Nuremberg, Erlangen, Germany.

Early enteral nutrition (EEN) represents the current standard of care for patients treated in general intensive care units (ICU). Specific nutritional recommendations for patients receiving dedicated neurocritical care are not established. This study investigated associations of EEN with clinical outcomes for patients suffering from intracerebral hemorrhage treated at a neurological ICU (NICU). This retrospective cohort study included patients admitted to the NICU with atraumatic ICH over a 4-year period. Nutritional data, demographic, clinical, radiological, and laboratory characteristics were assessed. EEN was defined as any enteral nutrition within 48 hours after admission. Comparisons were undertaken for patients with EEN vs. those without, further propensity score (PS) matching (caliper 0.2; one: many) was used to account for baseline imbalances. Primary outcome was the modified Rankin Scale (0-3 = favorable, 4-6 = unfavorable) at 12 months, secondary outcomes comprised perihemorrhagic edema (PHE) volume, infectious complications during the hospital stay, and mRS at 3 months, as well as mortality rates at 3 and 12 months. Of 166 ICH-patients treated at the NICU, 51 (30.7%) patients received EEN, and 115 (69.3%) patients received no EEN (nEEN). After propensity score matching, calories delivered from enteral nutrition (EEN 161.4 [106.4-192.3] kcal/day vs. nEEN 0.0 [0.0-0.0], < 0.001) and the total calories (EEN 190.0 [126.0-357.0] kcal/day vs. nEEN 33.6 [0.0-190.0] kcal/day, < 0.001) were significantly different during the first 48 h admitted in NICU. Functional outcome at 12 months (mRS 4-6, EEN 33/43 [76.7%] vs. nEEN, 49/64 [76. 6%]; = 1.00) was similar in the two groups. There were neither differences in mRS at 3 months, nor in mortality rates at 3 and 12 months between the two groups. EEN did not affect incidence of infective complications or gastrointestinal adverse events during the hospital stay; however, EEN was associated with significantly less extent of PHE evolution [maximum absolute PHE (OR 0.822, 95% CI 0.706-0.957, = 0.012); maximum relative PHE (OR 0.784, 95% CI 0.646-0.952, = 0.014)]. In our study, EEN was associated with reduced PHE in ICH-patients treated at a NICU. However, this observation did not translate into improved survival or functional outcome at 3 and 12 months.
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http://dx.doi.org/10.3389/fneur.2021.665791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093818PMC
April 2021

MiR-205-5p suppresses angiogenesis in gastric cancer by downregulating the expression of VEGFA and FGF1.

Exp Cell Res 2021 Jul 4;404(2):112579. Epub 2021 May 4.

Department of General Surgery, Peking University First Hospital, Beijing, 100034, China. Electronic address:

Anti-angiogenic therapy represents one of the most promising treatment modalities for human cancers. However, the response to antiangiogenic therapy in gastric cancer (GC) remains dismal. To help identify new strategies for antiangiogenic therapy in GC, we evaluated miR-205-5p expression in GC tissues from TCGA database and our hospital, and its functions in angiogenesis were explored in vitro and in vivo. We investigated miR-205-5p expression and microvessel densities (MVDs) in GC tissues and liver metastases from patients. The function and mechanisms of miR-205-5p were examined in human cell lines and in xenograft mouse models. Associations between miR-205-5p expression and clinical characteristics were analyzed using either Pearson's χ test or Fisher's exact test. Differences in overall survival (OS) distributions were evaluated using the log-rank test. Differences in measurement data were compared using Student's t-test and one-way ANOVA. We found that miR-205-5p expression was downregulated in GC tissues and was negatively correlated with CD31 expression in both TCGA and our clinical samples. GC cell lines expressed low levels of miR-205-5p, and miR-205-5p upregulation significantly impaired the proliferation and angiogenesis of GC cells. Moreover, vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 1 (FGF1) expression and activation of extracellular-related kinase (ERK) signaling were suppressed by miR-205-5p. MiR-205-5p inhibition promoted malignant phenotypes by enhancing VEGFA and FGF1 expression, as well as the activation of ERK signaling. Angiogenesis and ERK signaling were decreased in response to VEGFA and FGF1 downregulation induced by miR-205-5p overexpression. The dual-luciferase reporter assay showed that VEGFA and FGF1 were direct targets of miR-205-5p. Xenograft mouse models revealed that miR-205-5p suppressed tumor growth by inhibiting neovascularization. Altogether, these results demonstrate that miR-205-5p suppresses angiogenesis in GC by attenuating the expression of VEGFA and FGF1, indicating that upregulation of miR-205-5p may represent as an antiangiogenic therapy for GC.
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http://dx.doi.org/10.1016/j.yexcr.2021.112579DOI Listing
July 2021

Imaging Parameters Predict Recurrence After Transient Ischemic Attack or Minor Stroke Stratified by ABCD Score.

Stroke 2021 Jun 5;52(6):2007-2015. Epub 2021 May 5.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (J.J., Y.S., A.W., Y.Z., Y.J., L.L., X.Z., Yilong Wang, Z.L., H.L., X.M., Yongjun Wang).

Background And Purpose: Whether imaging parameters would independently predict stroke recurrence in low-risk minor ischemic stroke (MIS) or transient ischemic attack (TIA) according to traditional score system (such as ABCD score, which was termed on the basis of the initials of the five factors: age, blood pressure, clinical features, duration, diabetes) remains unclear. We sought to evaluate the association between imaging parameters and 1-year stroke recurrence in patients with TIA or MIS in different risk stratum stratified by ABCD score.

Methods: We included patients with TIA and MIS (National Institutes of Health Stroke Scale score ≤3) with complete baseline vessel and brain imaging data from the Third China National Stroke Registry III. Patients were categorized into different risk groups based on ABCD score (low risk, 0-3; moderate risk, 4-5; and high risk, 6-7). The primary outcome was stroke recurrence within 1 year. Multivariable Cox proportional-hazards regression models were used to assess whether imaging parameters (large artery stenosis, infarction number) were independently associated with stroke recurrence.

Results: Of the 7140 patients included, 584 patients experienced stroke recurrence within 1 year. According to the ABCD score, large artery stenosis was associated with higher stroke recurrence in both low-risk (adjusted hazard ratio, 1.746 [95% CI, 1.200-2.540]) and moderate-risk group (adjusted hazard ratio, 1.326 [95% CI, 1.042-1.687]) but not in the high-risk group (>0.05). Patients with multiple acute infarctions or single acute infarction had a higher risk of recurrent stroke than those with no infarction in both low- and moderate-risk groups, but not in the high-risk group.

Conclusions: Large artery stenosis and infarction number were independent predictors of 1-year stroke recurrence in low-moderate risk but not in high-risk patients with TIA or MIS stratified by ABCD score. This finding emphasizes the importance of early brain and vascular imaging evaluation for risk stratification in patients with TIA or MIS.
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http://dx.doi.org/10.1161/STROKEAHA.120.032424DOI Listing
June 2021

Association of Polyvascular Disease and Elevated Interleukin-6 With Outcomes in Acute Ischemic Stroke or Transient Ischemic Attack.

Front Neurol 2021 13;12:661779. Epub 2021 Apr 13.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Polyvascular disease (PolyVD) and interleukin (IL)-6 are associated with poor outcomes in patients with stroke respectively. However, whether combined PolyVD and elevated IL-6 levels would increase the risk of poor outcomes of stroke patients is yet unclear. Data were obtained from the Third China National Stroke Registry (CNSR-III). PolyVD was defined as acute ischemic stroke (AIS) or transient ischemic attack (TIA) with coronary artery disease (CAD) and/or peripheral artery disease (PAD). Patients were divided into four groups according to the combination of vascular beds number (non-PolyVD or PolyVD) and IL-6 levels (IL-6 < 2.64 pg/mL or IL-6 ≥ 2.64 pg/mL). The primary outcome was a recurrent stroke at 1-year follow-up. Cox proportional hazard models were employed to identify the association of the combined effect of PolyVD and IL-6 with the prognosis of patients. A total of 10,773 patients with IL-6 levels and 1-year follow-up were included. The cumulative incidence of recurrent stroke was 9.87% during the 1-year follow-up. Compared to non-PolyVD and IL-6<2.64 pg/mL patients, patients had non-PolyVD with IL-6 ≥ 2.64 pg/mL (HR 1.245 95%CI 1.072-1.446; < 0.001) and PolyVD with IL-6 <2.64 pg/mL (HR 1.251 95%CI 1.002-1.563; = 0.04) were associated with an increased risk of recurrent stroke during 1-year follow-up. Likewise, patients with PolyVD and IL-6 ≥ 2.64 pg/mL (HR 1.290; 95% CI 1.058-1.572; = 0.01) had the highest risk of recurrent stroke at 1-year follow-up among groups. PolyVD and elevated IL-6 levels are both associated with poor outcomes in patients with AIS or TIA. Moreover, the combination of them increases the efficiency of stroke risk stratification compared with when used alone. More attention and intensive treatment should be given to those patients with both PolyVD and elevated IL-6 levels.
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http://dx.doi.org/10.3389/fneur.2021.661779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076541PMC
April 2021

Antiviral Activity of Isoimperatorin Against Influenza A Virus and its Inhibition of Neuraminidase.

Front Pharmacol 2021 13;12:657826. Epub 2021 Apr 13.

Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, China.

Influenza A virus (IAV) poses a severe threat to human health and is a major public health problem worldwide. As global anti-influenza virus drug resistance has increased significantly, there is an urgent need to develop new antiviral drugs, especially drugs from natural products. Isoimperatorin, an active natural furanocoumarin, exhibits a broad range of pharmacologic activities including anticoagulant, analgesic, anti-inflammatory, antibacterial, anti-tumor, and other pharmacological effects, so it has attracted more and more attention. In this study, the antiviral and mechanistic effects of isoimperatorin on influenza A virus were studied. Isoimperatorin illustrated a broad-spectrum antiviral effect, especially against the A/FM/1/47 (H1N1), A/WSN/33 (H1N1, S31N, amantadine resistant), A/Puerto Rico/8/34 (H1N1), and A/Chicken/Guangdong/1996 (H9N2) virus strains. The experimental results of different administration modes showed that isoimperatorin had the best antiviral activity under the treatment mode. Further time-of-addition experiment results indicated that when isoimperatorin was added at the later stage of the virus replication cycle (6-8 h, 8-10 h), it exhibited an effective antiviral effect, and the virus yield was reduced by 81.4 and 84.6%, respectively. In addition, isoimperatorin had no effect on the expression of the three viral RNAs (mRNA, vRNA, and cRNA). Both the neuraminidase (NA) inhibition assay and CETSA demonstrated that isoimperatorin exerts an inhibitory effect on NA-mediated progeny virus release. The molecular docking experiment simulated the direct interaction between isoimperatorin and NA protein amino acid residues. In summary, isoimperatorin can be used as a potential agent for the prevention and treatment of influenza A virus.
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http://dx.doi.org/10.3389/fphar.2021.657826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077232PMC
April 2021

Metabolic disposition of the EGFR covalent inhibitor furmonertinib in humans.

Acta Pharmacol Sin 2021 Apr 29. Epub 2021 Apr 29.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201210, China.

Furmonertinib was designed for the treatment of non-small cell lung cancer (NSCLC) patients with EGFR T790M mutation. In this study, we investigated the metabolic disposition and mass balance in humans and tissue distribution in rats. After a single oral administration of 97.9 μCi/81.5 mg [C]-furmonertinib mesylate to six healthy male volunteers, the absorption process of furmonertinib was fast with a t of total plasma radioactivity at 0.75 h. Afterward, furmonertinib was extensively metabolized, with the parent drug and active metabolite AST5902 accounting for 1.68% and 0.97% of total radioactivity in plasma. The terminal t of total radioactivity in plasma was as long as 333 h, suggesting that the covalent binding of drug-related substances to plasma proteins was irreversible to a great extent. The most abundant metabolites identified in feces were desmethyl metabolite (AST5902), cysteine conjugate (M19), and parent drug (M0), which accounted for 6.28%, 5.52%, and 1.38% of the dose, respectively. After intragastric administration of 124 μCi/9.93 mg/kg [C]-furmonertinib to rats, drug-related substances were widely and rapidly distributed in tissues within 4 h. The concentration of total radioactivity in the lung was 100-fold higher than that in rat plasma, which could be beneficial to the treatment of lung cancer. Mass balance in humans was achieved with 77.8% of the administered dose recovered in excretions within 35 days after administration, including 6.63% and 71.2% in urine and feces, respectively. In conclusion, [C]-furmonertinib is completely absorbed and rapidly distributed into lung tissue, extensively metabolized in humans, presented mostly as covalent conjugates in plasma, and slowly eliminated mostly via fecal route.
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http://dx.doi.org/10.1038/s41401-021-00667-8DOI Listing
April 2021

Artificial electrochemically active biofilm for improved sensing performance and quickly devising of water quality early warning biosensors.

Water Res 2021 Jun 17;198:117164. Epub 2021 Apr 17.

State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, PR China. Electronic address:

A major challenge for devising an electrochemically active biofilm (EAB)-based biosensor for real-time water quality early-warning is the formation of EAB that requires several days to weeks. Besides the onerous and time-consuming preparation process, the naturally formed EABs are intensively concerned as they can hardly deliver repeatable electrical signals even at identical experimental conditions. To address these concerns, this study employed sodium alginate as immobilization agent to encapsulate Shewanella oneidensis MR-1 and prepared EAB for devising a biosensor in a short period of less than 1 h. The artificial EAB were found capable of delivering highly consistent electrical signals with each other when fed with the same samples. Morphology and bioelectrochemical properties of the artificial EAB were investigated to provide interpretations for these findings. Different concentrations of bacteria and alginate in forming the EAB were investigated for their effects on the biosensor's sensitivity. Results suggested that lower concentration of bacteria would be beneficial until it increased to 0.06 (OD). Concentration of sodium alginate affected the sensitivity as well and 1% was found an optimum amount to serve in the formation of EAB. A long-term operation of the biosensor with artificial EAB for 110 h was performed. Clear warning signals for incoming toxicants were observed over random signal fluctuations. All results suggested that the artificial EAB electrode would support a rapid devised and highly sensitivity biosensor.
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http://dx.doi.org/10.1016/j.watres.2021.117164DOI Listing
June 2021

Effects of different temperatures and pH values on volatile fatty acids production during codigestion of food waste and thermal-hydrolysed sewage sludge and subsequent volatile fatty acids for polyhydroxyalkanoates production.

Bioresour Technol 2021 Aug 8;333:125149. Epub 2021 Apr 8.

State Key Joint Laboratory of Environmental Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, China. Electronic address:

The effects of temperature (35 °C and 55 °C) and pH (uncontrolled, 7 and 10) on volatile fatty acid (VFA) yields from anaerobic codigestion of food waste, and thermal-hydrolysed sewage sludge were investigated in this study. The results revealed that optimal conditions for VFA production occurred at 35 °C at pH 7 and at 10 and 55 °C at pH 7. The dominant bacterial genera associated with VFA production significantly differed when the temperature and pH were altered, including Prevotella, Lactobacillus, Bifidobacterium Megasphaera, Clostridium XlVa, and Coprothermobacter. A temperature of 35 °C at pH 7 favoured mixed acid-type fermentation, while a temperature of 35 °C at pH 10 and 55 °C at pH 7 favoured butyric acid-type fermentation. The maximal polyhydroxyalkanoate content accounted for 54.8% of the dry cell at 35 °C with pH 7 fermentative liquids and comprised 58.9% 3-hydroxybutyrate (3HB) and 41.1% 3-hydroxyvalerate (3HV).
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http://dx.doi.org/10.1016/j.biortech.2021.125149DOI Listing
August 2021

Rapid identification, isolation, and evaluation on anti-neuroinflammatory activity of limonoids derivatives from the root bark of Dictamnus dasycarpus.

J Pharm Biomed Anal 2021 Jun 18;200:114079. Epub 2021 Apr 18.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People's Republic of China. Electronic address:

A total of 49 limonoids derivatives were rapidly identified by UNIFI software and three new limonoids derivatives, named dasycarinone (1, DAS), isodictamdiol C (2) and dasycarinone A (3), along with nineteen known compounds, were isolated from the root bark of Dictamnus dasycarpus, named as "Baixianpi" in Chinese. Their structures were elucidated on the basis of spectroscopic data (UV, IR, HR-ESI-MS, NMR, CD spectra and OR). All the compounds were tested for anti-inflammatory activities by suppressing the nitric oxide (NO) production in lipopolysaccharide (LPS) induced BV-2 cells. DAS exhibited a strong anti-inflammatory activity with IC value of 1.8 μM. Nuclear Factor kappa B (NF-κB) luciferase assay and enzyme-linked immune sorbent assay indicated that DAS can suppress the release of inflammatory cytokines such as Tumor Necrosis Factor α (TNF-α), interleukin 6 (IL-6) via inactivating NF-κB signaling pathways. Moreover, we found that anti-inflammatory activities of obacunone-class are better than those of limonin-class by analyzing structure-activity relationship. Our results suggested that obacunone derivatives play an important role on anti-inflammation of Baixianpi. As a representative among them, DAS showed a strong anti-inflammatory activity via suppressing NF-κB signaling pathways.
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http://dx.doi.org/10.1016/j.jpba.2021.114079DOI Listing
June 2021

On the use of GBLUP and its extension for GWAS with additive and epistatic effects.

G3 (Bethesda) 2021 Apr 19. Epub 2021 Apr 19.

Department of Breeding Research, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) Gatersleben, 06466 Stadt Seeland, Germany.

Genomic best linear unbiased prediction (GBLUP) is the most widely used model for genome-wide predictions. Interestingly, it is also possible to perform genome-wide association studies (GWAS) based on GBLUP. Although the estimated marker effects in GBLUP are shrunken and the conventional test based on such effects has low power, it was observed that a modified test statistic can be produced and the result of test was identical to a standard GWAS model. Later, a mathematical proof was given for the special case that there is no fixed covariate in GBLUP. Since then, the new approach has been called "GWAS by GBLUP". Nevertheless, covariates such as environmental and subpopulation effects are very common in GBLUP. Thus, it is necessary to confirm the equivalence in the general case. Recently, the concept was generalized to GWAS for epistatic effects and the new approach was termed rapid epistatic mixed-model association analysis (REMMA) because it greatly improved the computational efficiency. However, the relationship between REMMA and the standard GWAS model has not been investigated. In this study, we first provided a general mathematical proof of the equivalence between" GWAS by GBLUP" and the standard GWAS model for additive effects. Then, we compared REMMA with the standard GWAS model for epistatic effects by a theoretical investigation and by empirical data analyses. We hypothesized that the similarity of the two models is influenced by the relative contribution of additive and epistatic effects to the phenotypic variance, which was verified by empirical and simulation studies.
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http://dx.doi.org/10.1093/g3journal/jkab122DOI Listing
April 2021

Association of Trimethylamine N-Oxide and Its Precursor With Cerebral Small Vessel Imaging Markers.

Front Neurol 2021 1;12:648702. Epub 2021 Apr 1.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

High plasma levels of trimethylamine N-oxide (TMAO) and its precursor choline have been linked to stroke; however, their association with cerebral small vessel disease remains unclear. Here we evaluated the association of plasma levels of TMAO and choline with imaging markers of cerebral small vessel disease, including white matter hyperintensities, lacunes, and cerebral microbleeds. We performed a baseline cross-sectional analysis of a multicenter hospital-based cohort study from 2015 to 2018. The data were collected from 30 hospitals in China and included 1,098 patients with ischemic stroke/transient ischemic attack aged ≥18 years. White matter hyperintensities, lacunes, and cerebral microbleeds were evaluated with the patients' demographic, clinical, and laboratory information removed. White matter hyperintensities were rated using the Fazekas visual grading scale, while the degree of severity of the lacunes and cerebral microbleeds was defined by the number of lesions. Increased TMAO levels were associated with severe white matter hyperintensities [adjusted odds ratio (aOR) for the highest vs. lowest quartile, 1.5; 95% confidence interval (CI), 1.0-2.1, = 0.04]. High TMAO levels were more strongly associated with severe periventricular white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.6; 95% CI, 1.1-2.3, = 0.009) than deep white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.3; 95% CI, 0.9-1.9, = 0.16). No significant association was observed between TMAO and lacunes or cerebral microbleeds. Choline showed trends similar to that of TMAO in the association with cerebral small vessel disease. In patients with ischemic stroke or transient ischemic attack, TMAO and choline appear to be associated with white matter hyperintensities, but not with lacunes or cerebral microbleeds; TMAO and choline were associated with increased risk of a greater periventricular, rather than deep, white matter hyperintensities burden.
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http://dx.doi.org/10.3389/fneur.2021.648702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047127PMC
April 2021

COPB2: A Novel Prognostic Biomarker That Affects Progression of HCC.

Biomed Res Int 2021 20;2021:6648078. Epub 2021 Mar 20.

Department of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China.

Purpose: This study is aimed at investigating the expression, underlying biological function, and clinical significance of coatomer protein complex subunit beta 2 (COPB2) in hepatocellular carcinoma (HCC).

Methods: HCC-related data were extracted from The Cancer Genome Atlas (TCGA) database, International Cancer Genome Consortium (ICGC) database, and Gene Expression Omnibus (GEO) database. A logistic regression module was applied to analyze the relationship between the expression of COPB2 and clinicopathologic characteristics. The Cox proportional hazard regression model and Kaplan-Meier method were used for survival analysis. Gene set enrichment analysis (GSEA) was used to annotate the underlying biological functions. Loss-of-function experiments were conducted to determine the underlying mechanisms.

Results: COPB2 was overexpressed in HCC, and high expression of COPB2 was significantly correlated with higher alpha fetoprotein (AFP) (odds ratio (OR) = 1.616, >20 vs. ≤20, < 0.05), stage (OR = 1.744, III vs. I, < 0.05), and grade (OR = 1.746, G4+G3 vs. G2+G1, < 0.05). Kaplan-Meier survival analysis showed that HCC patients with high COPB2 expression had a worse prognosis than those with low COPB2 expression ( < 0.0001 for TCGA cohort, < 0.05 for ICGC cohort). The univariate Cox (hazard ratio (HR) = 1.068, < 0.0001) and multivariate Cox (HR = 2.011, < 0.05) regression analyses suggested that COPB2 was an independent risk factor. GSEA showed that mTOR and other tumor-related signaling pathways were differentially enriched in the high COPB2 expression phenotype. Silencing of COPB2 inhibited the proliferation, migration, and invasion abilities by suppressing epithelial-mesenchymal transition and mTOR signaling.

Conclusion: COPB2 is a novel prognostic biomarker and a promising therapeutic target for HCC.
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http://dx.doi.org/10.1155/2021/6648078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007342PMC
May 2021

Long Noncoding RNA RUNXOR Promotes Myeloid-Derived Suppressor Cell Expansion and Functions via Enhancing Immunosuppressive Molecule Expressions during Latent HIV Infection.

J Immunol 2021 May 5;206(9):2052-2060. Epub 2021 Apr 5.

Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN;

RUNX1 overlapping RNA (RUNXOR) is a long noncoding RNA and a key regulator of myeloid-derived suppressor cells (MDSCs) via targeting runt-related transcription factor 1 (RUNX1). We and others have previously reported MDSC expansion and inhibition of host immune responses during viral infections; however, the mechanisms regulating MDSC differentiation and suppressive functions, especially the role of RUNXOR-RUNX1 in the regulation of MDSCs in people living with HIV (PLHIV), remain unknown. In this study, we demonstrate that RUNXOR and RUNX1 expressions are upregulated in MDSCs that expand and accumulate in human PBMCs derived from PLHIV. We found that the upregulation of RUNXOR and RUNX1 is associated with the expressions of several key immunosuppressive molecules, including arginase 1, inducible NO synthase, STAT3, IL-6, and reactive oxygen species. RUNXOR and RUNX1 could positively regulate each other's expression and control the expressions of these suppressive mediators. Specifically, silencing RUNXOR or RUNX1 expression in MDSCs from PLHIV attenuated MDSC expansion and immunosuppressive mediator expressions, whereas overexpressing RUNXOR in CD33 myeloid precursors from healthy subjects promoted their differentiation into MDSCs and enhanced the expression of these mediators. Moreover, loss of RUNXOR-RUNX1 function in MDSCs improved IFN-γ production from cocultured autologous CD4 T cells derived from PLHIV. These results suggest that the RUNXOR-RUNX1 axis promotes the differentiation and suppressive functions of MDSCs via regulating multiple immunosuppressive signaling molecules and may represent a potential target for immunotherapy in conjunction with antiviral therapy in PLHIV.
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http://dx.doi.org/10.4049/jimmunol.2001008DOI Listing
May 2021

Comparison of Deep-Sea Picoeukaryotic Composition Estimated from the V4 and V9 Regions of 18S rRNA Gene with a Focus on the Hadal Zone of the Mariana Trench.

Microb Ecol 2021 Apr 3. Epub 2021 Apr 3.

College of Marine Life Sciences, Frontiers Science Center for Deep Ocean Multispheres and Earth System, Ocean University of China, Qingdao, China.

Diversity of microbial eukaryotes is estimated largely based on sequencing analysis of the hypervariable regions of 18S rRNA genes. But the use of different regions of 18S rRNA genes as molecular markers may generate bias in diversity estimation. Here, we compared the differences between the two most widely used markers, V4 and V9 regions of the 18S rRNA gene, in describing the diversity of epipelagic, bathypelagic, and hadal picoeukaryotes in the Challenger Deep of the Mariana Trench, which is a unique and little explored environment. Generally, the V9 region identified more OTUs in deeper waters than V4, while the V4 region provided greater Shannon diversity than V9. In the epipelagic zone, where Alveolata was the dominant group, picoeukaryotic community compositions identified by V4 and V9 markers are similar at different taxonomic levels. However, in the deep waters, the results of the two datasets show clear differences. These differences were mainly contributed by Retaria, Fungi, and Bicosoecida. The primer targeting the V9 region has an advantage in amplifying Bicosoecids in the bathypelagic and hadal zone of the Mariana Trench, and its high abundance in V9 dataset pointed out the possibility of Bicosoecids as a dominant group in this environment. Chrysophyceae, Fungi, MALV-I, and Retaria were identified as the dominant picoeukaryotes in the bathypelagic and hadal zone and potentially play important roles in deep-sea microbial food webs and biogeochemical cycling by their phagotrophic, saprotrophic, and parasitic life styles. Overall, the use of different markers of 18S rRNA gene allows a better assessment and understanding of the picoeukaryotic diversity in deep-sea environments.
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http://dx.doi.org/10.1007/s00248-021-01747-2DOI Listing
April 2021

Keypoint-Based Robotic Grasp Detection Scheme in Multi-Object Scenes.

Sensors (Basel) 2021 Mar 18;21(6). Epub 2021 Mar 18.

College of Information Science and Engineering, Northeastern University, Shenyang 110819, China.

Robot grasping is an important direction in intelligent robots. However, how to help robots grasp specific objects in multi-object scenes is still a challenging problem. In recent years, due to the powerful feature extraction capabilities of convolutional neural networks (CNN), various algorithms based on convolutional neural networks have been proposed to solve the problem of grasp detection. Different from anchor-based grasp detection algorithms, in this paper, we propose a keypoint-based scheme to solve this problem. We model an object or a grasp as a single point-the center point of its bounding box. The detector uses keypoint estimation to find the center point and regress to all other object attributes such as size, direction, etc. Experimental results demonstrate that the accuracy of this method is 74.3% in the multi-object grasp dataset VMRD, and the performance on the single-object scene Cornell dataset is competitive with the current state-of-the-art grasp detection algorithm. Robot experiments demonstrate that this method can help robots grasp the target in single-object and multi-object scenes with overall success rates of 94% and 87%, respectively.
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http://dx.doi.org/10.3390/s21062132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002942PMC
March 2021

Efficacy, safety, and genetic analysis of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small-cell lung cancer: a phase 2b, multicentre, single-arm, open-label study.

Lancet Respir Med 2021 Mar 26. Epub 2021 Mar 26.

Shanghai Allist Pharmaceutical Technology, Shanghai, China.

Background: Furmonertinib (AST2818) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting both sensitising EGFR and EGFR Thr790Met (T790M) mutations. This study aimed to assess the efficacy and safety of furmonertinib in patients with EGFR T790M mutated advanced non-small-cell lung cancer (NSCLC).

Methods: This study was a single-arm, open-label, phase 2b study at 46 hospitals across mainland China. Patients with locally advanced or metastatic NSCLC with centrally confirmed EGFR T790M mutations in tumour tissue who progressed after first or second generation EGFR TKIs or with primary EGFR T790M mutations received furmonertinib 80 mg orally once daily. The primary endpoint was objective response rate. Efficacy was assessed by blinded independent central review as per the Response Evaluation Criteria in Solid Tumors (version 1.1) in all patients who had measurable disease at baseline and received at least one dose of furmonertinib. Safety was assessed as per the Common Terminology Criteria for Adverse Events (version 4.03) in all patients who received at least one dose of furmonertinib with at least one safety assessment during follow-up. This study is registered with ClinicalTrials.gov (NCT03452592) and is ongoing for survival follow-up.

Findings: From Jun 4, 2018, to Dec 8, 2018, 220 patients received furmonertinib treatment. All 220 patients were included in the efficacy and safety analyses. At the data cutoff point of Jan 29, 2020, 71 (32%) patients remained on treatment. The median duration of follow-up was 9·6 months (range 0·7-19·4). The objective response rate was 74% (163 of 220 [95% CI 68-80]). Grade 3 or higher adverse events occurred in 58 (26%) patients and treatment-related grade 3 or higher adverse events occurred in 25 (11%) patients. The most common all-cause grade 3 or higher adverse events were increased γ-glutamyltransferase (five; 2%), increased aspartate aminotransferase, increased alanine aminotransferase, hyponatraemia, hypertension, pulmonary infection, hypermagnesaemia, and pericardial effusion (three each; 1%). Treatment-related diarrhoea was reported in ten (5%) patients and rashes were reported in 16 (7%) patients, all grade 1-2. Serious adverse events were reported in 52 (24%) patients, of which 12 (5%) were possibly treatment-related as evaluated by the investigator.

Interpretation: Furmonertinib has promising efficacy and an acceptable safety profile for the treatment of patients with EGFR T790M mutated NSCLC. Furmonertinib is expected to become a new treatment option after first or second generation EGFR TKIs in the Chinese population.

Funding: Shanghai Allist Pharmaceutical Technology, Ministry of Science and Technology of the People's Republic of China, and Chinese Academy of Medical Sciences.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2213-2600(20)30455-0DOI Listing
March 2021