Publications by authors named "Ting Ma"

316 Publications

Globalization and environment: Effects of international trade on emission intensity reduction of pollutants causing global and local concerns.

Authors:
Ting Ma Yue Wang

J Environ Manage 2021 Jul 17;297:113249. Epub 2021 Jul 17.

School of Public Policy and Management, Tsinghua University, Beijing, China. Electronic address:

International trade's impact on the pollution reduction, especially varied reduction effects dealing with global or local pollutants has not been thoroughly researched empirically. We explored effects of international trade participation on both the carbon dioxide emission intensity and sulfur dioxide emission intensity with a panel data of 179 major countries during 20 years when globalization thrived. Carbon dioxide causing climate change is a global concern. While sulfur dioxide is one major air pollutant causing local health problems. Empirically, international trade participation mainly reduces carbon dioxide emission intensity but not sulfur dioxide emission intensity. Also, trade in goods form is more effective than in service form. However, international trade participation does little to improving a country's overall technology level, implying that regulation enhancement under international norm is the main mechanism. Compared with developed countries, developing countries can reduce both kinds of pollutant emission intensities more effectively by participating into international trade. A case study of China's entering into World Trade Organization (WTO)'s impact on pollutant reduction can provide more evidence. Also, developing countries with higher industrialization level experiences a bigger improvement in cleaner production. And developing countries with higher democratization level pay more attention to reduce local environmental concerns.
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http://dx.doi.org/10.1016/j.jenvman.2021.113249DOI Listing
July 2021

Rapid Hygiene Assay Sensitive to Cumulative Adenylate Homologues Exhibits Equal or Higher Frequencies of Soil Contamination Detection than Assay Limited to ATP Detection.

J Food Prot 2021 Jul 15. Epub 2021 Jul 15.

University of Wisconsin-Madison.

Based upon regulatory and food industry-driven food safety standards, there is a need for rapid, accurate methods for assessing sanitary conditions. A commonly utilized assay is based on the assessment of the biochemical molecule, adenosine triphosphate (ATP). A more recent assay (AXP) targets the cumulative presence of ATP and its dephosphorylated homologues, adenosine diphosphate (ADP) and adenosine monophosphate (AMP). Yet, there is little information that compares the practical performance of these two assays. This work examined these two assay types with a comparative study in a Grade A dairy foods processing plant and a licensed and inspected meat processing facility. A total of 1,920 concomitant analyses were conducted with main variables of assay type, processing facility type and hygiene zone category. Statistical process control methodology was used to calculate 95% confidence control limits (CL); data beyond those limits were considered contamination events. Results demonstrated that, overall, the AXP assay detected contamination events approximately two times more often than the ATP-only based assay. This increase in the rate of contamination event detection was especially more prevalent in the meat processing facility where, across all hygienic zones, there were 38 vs. 85 contaminations events detected for the ATP and AXP assays, respectively. Across hygiene zones, the AXP data displayed either an equal or increased incidence of soil detection compared to data from the ATP assay. This study provides applied evidence that assays solely dependent on ATP concentrations are less able to detect soil contaminants under conditions that favor ATP dephosphorylation reactions.
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http://dx.doi.org/10.4315/JFP-21-028DOI Listing
July 2021

Five distinct fucan sulfates from sea cucumber Pattalus mollis: Purification, structural characterization and anticoagulant activities.

Int J Biol Macromol 2021 Jul 9;186:535-543. Epub 2021 Jul 9.

School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China. Electronic address:

Fucan sulfates from echinoderm possess characteristic structures and various biological activities. Herein, comprehensive methods including enzymolysis, ion-exchange chromatography and size exclusion chromatography lead to the purification of five fucan sulfates (FSI, FSII, FSIII, FSIV, FSV) from the sea cucumber Pattalus mollis. Chemical composition analysis showed that they were all composed of l-fucose. Their sulfate content was determined by a conductimetric method. The molecular weight (Mw) of FSI, FSII, FSIII, FSIV and FSV were measured as 238.3 kDa, 81.0 kDa, 82.0 kDa, 23.2 kDa and 6.12 kDa, respectively. Detailed NMR spectroscopic analysis revealed that the structural sequence of FSI and FSII was →3)-l-Fuc-α(1→, where Fuc were Fuc (10%), Fuc (44%), Fuc (10%), Fuc (36%), that of FSIII was →4)-l-Fuc-(α1 → 4)-l-Fuc-(α1 → 4)-l-Fuc-(α1→, where Fuc and Fuc were in equal molar, and that FSIV was →4)-l-Fuc-(α1 → 4)-l-Fuc-(α1 → 4)-l-Fuc-(α1→4)-l-Fuc-(α1 → 4)-l-Fuc-(α1 → 4)-l-Fuc-(α1 → . This is the first report that such a diversity of fucan sulfates were obtained from the same sea cucumber species. Biological activity showed that FSI, FSII, FSIII and FSIV exhibited potent anticoagulant by prolonging the APTT. Among them, FSII, FSIII and FSIV showed the similar potency, while FSI owned the strongest. Structure-activity relationships analysis showed that molecular weight and sulfation degree should be the crucial factors for the activity.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.07.049DOI Listing
July 2021

[Analysis of platelet antibody screening in 38 840 inpatients].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Aug;37(8):736-740

Department of Blood Transfusion, Shaanxi Provincial People's Hospital, Xi'an 710068, China. *Corresponding authors, E-mail:

Objective To detect and analyze the distribution characteristics of platelet antibodies in inpatients and explore the causes of platelet antibodies, so as to provide data support for improving the quality of blood transfusion. Methods A total of 38 840 patients were selected. The platelet-related antibodies were detected by Capture-P solid-phase detection system, and the positive rate of antibodies was analyzed statistically. Results Of the 38840 inpatients, 3989 were positive for platelet antibodies, with a positive rate of 10.27%. The positive rates of male and female patients were 8.7% and 11.5%, respectively. The positive rate of platelet antibodies in patients under 18 years old was 6.98% which was significantly lower than that in patients ≥66 years old and 18~65 years old. The positive rates of patients with pregnancy history and blood transfusion history increased significantly, which were 14.4% and 14.7%, respectively. The positive rate of patients with blood system diseases and liver cirrhosis with gastrointestinal bleeding diseases was over 20%. The positive rates of patients in the Hematology Department, Intensive Care Department and Obstetrics Department ranked the top three, with the positive rates of 15.17%, 14.97%, and 13.67%, respectively. The positive rates of platelet antibodies in patients with blood types B and AB were lower than those in patients with blood types A and O. Conclusion In clinical platelet transfusion, the influence of the patients' age, gender, hospitalized diseases, hospitalized department and other factors on platelet antibodies should be considered to reduce the occurrence of platelet transfusion refractoriness.
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August 2021

Facile distribution of an alkaline microenvironment improves human bone marrow mesenchymal stem cell osteogenesis on a titanium surface through the ITG/FAK/ALP pathway.

Int J Implant Dent 2021 Jun 28;7(1):56. Epub 2021 Jun 28.

Department of Implantology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, People's Republic of China.

Purpose: Osseointegration at the titanium surface-bone interface is one of the key factors affecting the success rate of dental implants. However, the titanium surface always forms a passive oxide layer and impacts bone marrow-derived mesenchymal stem cell (BMSC) osteogenic differentiation after exposure to the atmosphere, which further leads to poor osseointegration. Given that wet storage helps prevent titanium aging and that weakly alkaline conditions stimulate BMSC osteogenic differentiation, the aim of the present study was to explore whether sodium bicarbonate, a well-known hydrogen ion (pH) buffer, forms an alkaline microenvironment on titanium surfaces to promote BMSC osteogenic differentiation.

Material And Methods: In this work, sand-blasted and acid-etched (SLA) titanium discs were soaked in 20 mM, 50 mM, 100 mM, and 200 mM sodium bicarbonate at room temperature for 5 min without rinsing. The influence of this surface modification on BMSC adhesion, proliferation, and osteogenic differentiation was measured. Additionally, cellular osteogenic differentiation-associated signaling pathways were evaluated.

Results: We showed that titanium discs treated with sodium bicarbonate created an extracellular environment with a higher pH for BMSCs than the normal physiological value for 5 days, strongly promoting BMSC osteogenic differentiation via the activation of integrin-focal adhesion kinase-alkaline phosphatase (Itg-FAK-ALP). In addition, the proliferation and adhesion of BMSCs were increased after alkaline treatment. These cellular effects were most significant with 100 mM sodium bicarbonate.

Conclusion: The results indicated that the titanium surface treated with sodium bicarbonate improved BMSC osteogenic differentiation mainly by creating an alkaline microenvironment, which further activated the Itg-FAK-ALP signaling pathway.

Clinical Relevance: Surfaces modified with 100 mM sodium bicarbonate had the highest initial pH value and thus showed the greatest potential to improve BMSC performance on titanium surfaces, identifying a novel conservation method for dental implants.
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http://dx.doi.org/10.1186/s40729-021-00341-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236422PMC
June 2021

HiAM: A Hierarchical Attention based Model for knowledge graph multi-hop reasoning.

Neural Netw 2021 Jun 9;143:261-270. Epub 2021 Jun 9.

University of Chinese Academy of Sciences, Beijing 100049, China; Institute of Information Engineering, Chinese Academy of Sciences, Beijing 100093, China. Electronic address:

Learning to reason in large-scale knowledge graphs has attracted much attention from research communities recently. This paper targets a practical task of multi-hop reasoning in knowledge graphs, which can be applied in various downstream tasks such as question answering, and recommender systems. A key challenge in multi-hop reasoning is to synthesize structural information (e.g., paths) in knowledge graphs to perform deeper reasoning. Existing methods usually focus on connection paths between each entity pair. However, these methods ignore predecessor paths before connection paths and regard entities and relations within every single path as equally important. With our observations, predecessor paths before connection paths can provide more accurate semantic representations. Furthermore, entities and relations in a single path contribute variously to the right answers. To this end, we propose a novel model HiAM (Hierarchical Attention based Model) for knowledge graph multi-hop reasoning. HiAM makes use of predecessor paths to provide more accurate semantics for entities and explores the effects of different granularities. Firstly, we extract predecessor paths of head entities and connection paths between each entity pair. Then, a hierarchical attention mechanism is designed to capture the information of different granularities, including entity/relation-level and path-level features. Finally, multi-granularity features are fused together to predict the right answers. We go one step further to select the most significant path as the explanation for predicted answers. Comprehensive experimental results demonstrate that our method achieves competitive performance compared with the baselines on three benchmark datasets.
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http://dx.doi.org/10.1016/j.neunet.2021.06.008DOI Listing
June 2021

Alteration of brain structural connectivity in progression of Parkinson's disease: A connectome-wide network analysis.

Neuroimage Clin 2021 Jun 6;31:102715. Epub 2021 Jun 6.

Department of Neurobiology, Neurology and Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Disease, Beijing, China. Electronic address:

Pinpointing the brain dysconnectivity in idiopathic rapid eye movement sleep behaviour disorder (iRBD) can facilitate preventing the conversion of Parkinson's disease (PD) from prodromal phase. Recent neuroimage investigations reported disruptive brain white matter connectivity in both iRBD and PD, respectively. However, the intrinsic process of the human brain structural network evolving from iRBD to PD still remains largely unknown. To address this issue, 151 participants including iRBD, PD and age-matched normal controls were recruited to receive diffusion MRI scans and neuropsychological examinations. The connectome-wide association analysis was performed to detect reorganization of brain structural network along with PD progression. Eight brain seed regions in both cortical and subcortical areas demonstrated significant structural pattern changes along with the progression of PD. Applying machine learning on the key connectivity related to these seed regions demonstrated better classification accuracy compared to conventional network-based statistic. Our study shows that connectome-wide association analysis reveals the underlying structural connectivity patterns related to the progression of PD, and provide a promising distinct capability to predict prodromal PD patients.
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http://dx.doi.org/10.1016/j.nicl.2021.102715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209844PMC
June 2021

Characterization of the immune cell infiltration landscape in bladder cancer to aid immunotherapy.

Arch Biochem Biophys 2021 Sep 9;708:108950. Epub 2021 Jun 9.

Diabetes Center, Zhejiang Provincial Key Laboratory of Pathophysiology, Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo, China. Electronic address:

The tumor microenvironment (TME) is composed mainly of tumor cells, tumorinfiltrating immune cells, and matrix components. Recent clinical studies have indicated that tumor immune cell infiltration (ICI) is related to the sensitivity of immunotherapy and the prognosis of patients with bladder cancer (BC). Nevertheless, up to now, the landscape of immune infiltration in BC has not been clearly defined. Here we present two algorithms to reveal the landscape of ICI in 277 cases of BC. Two kinds of ICI patterns were established, and ICI scores were based on the analysis of the main components. In sub-types with high ICI scores, we found highly expressed immunecheckpoint and activated transforming growth factor b and WNT signal pathways. These might be the cause of poor prognosis. A low ICI score indicated a better prognosis. Our study showed that ICI scores in immunotherapy could be a valid biomarker for the prognosis of patients and a predictive indicator. The evaluation of ICI patterns of a larger cohort of samples would expand our cognition of TME, and the present study might guide the strategies of immunotherapy for patients with BC.
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http://dx.doi.org/10.1016/j.abb.2021.108950DOI Listing
September 2021

Quantifying internal charge transfer and mixed ion-electron transfer in conjugated radical polymers.

Chem Sci 2020 Aug 31;11(36):9962-9970. Epub 2020 Aug 31.

Artie McFerrin Department of Chemical Engineering, Texas A&M University College Station TX USA

Macromolecular radicals are receiving growing interest as functional materials in energy storage devices and in electronics. With the need for enhanced conductivity, researchers have turned to macromolecular radicals bearing conjugated backbones, but results thus far have yielded conjugated radical polymers that are inferior in comparison to their non-conjugated partners. The emerging explanation is that the radical unit and the conjugated backbone (both being redox active) transfer electrons between each other, essentially "quenching" conductivity or capacity. Here, the internal charge transfer process is quantified using a polythiophene loaded with 0, 25, or 100% nitroxide radicals (2,2,6,6-tetramethyl-1-piperidinyloxy [TEMPO]). Importantly, deconvolution of the cyclic voltammograms shows mixed faradaic and non-faradaic contributions that contribute to the internal charge transfer process. Further, mixed ion-electron transfer is determined for the 100% TEMPO-loaded conjugated radical polymer, from which it is estimated that one triflate anion and one propylene carbone molecule are exchanged for every electron. Although these findings indicate the reason behind their poor conductivity and capacity, they point to how these materials might be used as voltage regulators in the future.
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http://dx.doi.org/10.1039/d0sc03567jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162116PMC
August 2020

Gut Microbiome Composition Associated With Major Depressive Disorder and Sleep Quality.

Front Psychiatry 2021 21;12:645045. Epub 2021 May 21.

Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Beijing, China.

The microbiota-gut-brain axis plays a critical role in the pathogenesis of major depressive disorder (MDD) and related subclinical symptoms. However, studies on the gut microbiota in MDD are inconsistent, and data on MDD's effects on sleep are lacking. This study aimed to analyze the gut microbiota composition and sleep quality of patients with MDD. We performed 16S rRNA sequencing of stool samples from 36 patients with MDD and 45 healthy controls (HC). Sleep quality was assessed using the Pittsburgh Sleep Quality Index, depressive severity with the Hamilton Depression Scale, and insomnia severity using the Insomnia Severity Index. Forty-eight microbiota targets showed significant differences between MDD and HC. In MDD, six microbiota targets were associated with the severity of depression, 11 with sleep quality, and 3 with sleep severity. At the genus level, was simultaneously related to depression and sleep quality, while was more closely related to sleep problems. and were associated with sleep quality independent of the severity of depression. In conclusion, the present findings enable a better understanding of the relationship between gut microbiota and MDD-related symptoms. Gut microbiota alterations may become potential biomarkers and/or treatment targets for sleep quality in MDD.
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http://dx.doi.org/10.3389/fpsyt.2021.645045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175648PMC
May 2021

Prognostic Significance of Blood-Based Multi-cancer Detection in Plasma Cell-Free DNA.

Clin Cancer Res 2021 Jun 4. Epub 2021 Jun 4.

Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota.

Purpose: We recently reported the development of a cell-free DNA (cfDNA) targeted methylation (TM)-based sequencing approach for a multi-cancer early detection (MCED) test that includes cancer signal origin prediction. Here, we evaluated the prognostic significance of cancer detection by the MCED test using longitudinal follow-up data.

Experimental Design: As part of a Circulating Cell-free Genome Atlas (CCGA) substudy, plasma cfDNA samples were sequenced using a TM approach, and machine learning classifiers predicted cancer status and cancer signal origin. Overall survival (OS) of cancer participants in the first 3 years of follow-up was evaluated in relation to cancer detection by the MCED test and clinical characteristics.

Results: Cancers not detected by the MCED test had significantly better OS ( < 0.0001) than cancers detected, even after accounting for other covariates, including clinical stage and method of clinical diagnosis (i.e., standard-of-care screening or clinical presentation with signs/symptoms). Additionally, cancers not detected by the MCED test had better OS than was expected when data were adjusted for age, stage, and cancer type from the Surveillance, Epidemiology, and End Results (SEER) program. In cancers with current screening options, the MCED test also differentiated more aggressive cancers from less aggressive cancers ( < 0.0001).

Conclusions: Cancer detection by the MCED test was prognostic beyond clinical stage and method of diagnosis. Cancers not detected by the MCED test had better prognosis than cancers detected and SEER-based expected survival. Cancer detection and prognosis may be linked by the underlying biological factor of tumor fraction in cfDNA.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-0417DOI Listing
June 2021

Genomic analysis and preclinical xenograft model development identify potential therapeutic targets for MYOD1-mutant soft-tissue sarcoma of childhood.

J Pathol 2021 Jun 4. Epub 2021 Jun 4.

Division of Pediatric Hematology and Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.

The myogenic differentiation 1 gene (MYOD1) p.L122R somatic mutation was first discovered in a subset of clinically aggressive embryonal rhabdomyosarcomas and has since been described in both pediatric and adult spindle cell/sclerosing rhabdomyosarcomas. Relatively little is known about the clinical, molecular, and histopathological features of these tumors in children. In order to further characterize the genomic and clinical features of pediatric MYOD1-mutant sarcomas, we evaluated a cohort of soft-tissue sarcoma patients treated at Texas Children's Hospital. Tumor DNA was subjected to next-generation panel sequencing and/or Sanger sequencing of the MYOD1 hotspot mutation. The MYOD1 p.L122R mutation was identified in six tumors, with a variant allele fraction greater than 0.8 in three cases, suggestive of loss of heterozygosity. One sclerosing rhabdomyosarcoma lacking the MYOD1 hotspot mutation was observed to have a MYOD1 copy number gain, also with evidence of loss of heterozygosity. Cancer gene panel sequencing revealed potentially targetable alterations in six of seven (86%) patients with MYOD1 alterations, including four patients with an alteration in the PI3K-AKT pathway: two hotspot PIK3CA mutations and deletions in PTEN and TSC2. On histopathologic review, MYOD1-altered tumors exhibited spindle and/or round cells and varying degrees of hyaline sclerosis. At last follow-up, six patients had died of disease and the seventh progressed early and was subsequently lost to follow-up. Both pre- and post-therapy patient-derived xenograft models were generated from one patient's tumor. These models were confirmed to harbor the MYOD1 and PIK3CA mutations seen in the primary tumor and were shown to be sensitive to PI3K/mTOR inhibition in vitro and in vivo. In conclusion, this study adds to recent reports describing the clinicopathologic and genomic features of MYOD1-altered soft-tissue sarcomas in children, including dismal prognosis and potential molecular targets for therapy. The novel preclinical models developed will facilitate further biological and preclinical study of this rare and aggressive tumor. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/path.5736DOI Listing
June 2021

Lateral flow immunoassay based on gold magnetic nanoparticles for the protein quantitative detection: Prostate-specific antigen.

Anal Biochem 2021 Aug 29;627:114265. Epub 2021 May 29.

College of Life Sciences, Northwest University, Xi'an, Shaanxi, 710069, China. Electronic address:

Point-of-care testing (POCT) demands for rapidly obtaining test results by means of portable analytical instruments and auxiliary reagents at the sampling site. It's important for tumor marker to be recognized and detected in early clinical diagnosis. Many studies focused on producing small portable devices that would allow fast, accurate, and on-site detection. This study aimed to report a magnetic quantitative lateral flow immunoassay (LFIA) system based on poly (acrylic acid) (PAA)-modified gold magnetic nanoparticles (PGMNs) for detecting prostate-specific antigen (PSA) qualitatively and quantitatively. The result was easily achievable with a portable magnetic reader within 15 min. Under optimal conditions, as low as 0.17 ng/mL PSA could be detected. The method was validated using a well-established Solin electrochemiluminescence immunoassay and showed high consistency in detecting 84 serum samples (R = 0.98). The quantitative LFIA based on PGMNs established in this study was proven to be rapid, accurate, sensitive, and inexpensive. As a POCT, it can be potentially developed for the quantitative diagnosis of other disease-related protein biomarkers.
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http://dx.doi.org/10.1016/j.ab.2021.114265DOI Listing
August 2021

A population-based prospective study on rest-activity rhythm and mild cognitive impairment among Hong Kong healthy community-dwelling older adults.

Neurobiol Sleep Circadian Rhythms 2021 May 16;10:100065. Epub 2021 Apr 16.

JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.

Background: Relatively few studies investigated the association between rest-activity circadian rhythm and cognitive impairment in population-based study, and the evidence from Asian populations is sparse. We aimed to examine the relationship of actigraphy measured rest-activity circadian rhythm with mild cognitive impairment (MCI) or cognitive impairment in Hong Kong healthy community-dwelling older adults.

Methods: We recruited 174 Hong Kong healthy adults aged ≥65 years (36 male vs. 138 female) during April-September 2018, and followed up them for 12 months. Participants were invited to wear wrist actigraphy for 7 days in both baseline and follow-up study. We used the actigraph data to calculate their midline statistic of rhythm (MESOR), amplitude, acrophase and percent rhythm. Montreal Cognitive Assessment (MoCA) was used to assess their cognitive scores at baseline and follow-up. Multivariate logistic regression model was performed to estimate the association of rest-activity circadian rhythm parameters with MCI; whilst multinomial logistic regression model was used to examine the association between rhythm parameters and changes of cognitive scores (i.e., worsen: <-1, stable: -1 to 1, better cognition: ≥2) after 12-months follow-up respectively.

Results: There was no association between rest-activity circadian rhythm parameters and MCI or cognitive impairment at baseline. Compared to those with an averaged value of acrophase (1:24pm-3:00pm), results of multinominal logistic regression showed that participants with a delayed acrophase (after 3:00pm) were less likely to have better cognition (adjusted odds ratio (AOR) = 0.32, 95% confidence interval (CI) = 0.11-0.88). Upon one year of follow-up, participants who delayed their acrophase for 24 min than their baseline measurements were also less likely to have better cognitive functions (AOR = 0.26, 95%CI = 0.08-0.79).

Conclusions: Results from both the baseline survey and follow-up study consistently confirmed that older adults, especially in light of the majority of participants being the females, with delayed acrophase were less likely to have better cognition in the Asian population.
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http://dx.doi.org/10.1016/j.nbscr.2021.100065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091051PMC
May 2021

Thermostable and rheological properties of natural and genetically engineered xanthan gums in different solutions at high temperature.

Int J Biol Macromol 2021 Jul 11;182:1208-1217. Epub 2021 May 11.

Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China. Electronic address:

Thermostability is an important indicator to evaluate xanthan applied in the oilfield industry. Besides reductive agents, salts, and pH, the inherent primary structure is also an important determinant of thermostability. In this work, the thermal conformational transition and degradation of natural xanthan XG and variants XG-A0, XG-AA, and XG-0P dissolved in different solvents were compared. Acetylated XG-A0 and XG-AA both showed the highest initial conformational transition temperature (Tm) in distilled water, NaCl, and CaCl brines. Additionally, the variant XG-A0 dissolved in water was more thermostable although its acetyl group was hydrolyzed easily after a hot-rolling test at 110 °C. Thermostability could be reinforced by adding antioxidant NaSO and saturated NaCl through improving Tm value or inhibiting degradation of the molecular chain and acyl groups. Furthermore, pyruvyl-rich XG-0P dissolved in saturated NaCl showing multi-stranded helix structure was also stable after a hot-rolling process. Therefore, xanthan variants, as biological products, will have broader application potential in the oilfield industry.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.008DOI Listing
July 2021

Magnetic resonance imaging-guided stereotactic body radiotherapy for prostate cancer (mirage): a phase iii randomized trial.

BMC Cancer 2021 May 11;21(1):538. Epub 2021 May 11.

Department of Radiation Oncology, University of California Los Angeles, 200 Medical Plaza Driveway, Suite # B265, Medical Plaza Driveway, Los Angeles, CA, 90095, USA.

Background: Stereotactic body radiotherapy (SBRT) is becoming increasingly used in treating localized prostate cancer (PCa), with evidence showing similar toxicity and efficacy profiles when compared with longer courses of definitive radiation. Magnetic resonance imaging (MRI)-guided radiotherapy has multiple potential advantages over standard computed tomography (CT)-guided radiotherapy, including enhanced prostate visualization (abrogating the need for fiducials and MRI fusion), enhanced identification of the urethra, the ability to track the prostate in real-time, and the capacity to perform online adaptive planning. However, it is unknown whether these potential advantages translate into improved outcomes. This phase III randomized superiority trial is designed to prospectively evaluate whether toxicity is lower after MRI-guided versus CT-guided SBRT.

Methods: Three hundred men with localized PCa will be randomized in a 1:1 ratio to SBRT using CT or MRI guidance. Randomization will be stratified by baseline International Prostate Symptom Score (IPSS) (≤15 or > 15) and prostate gland volume (≤50 cc or > 50 cc). Five fractions of 8 Gy will be delivered to the prostate over the course of fourteen days, with or without hormonal therapy and elective nodal radiotherapy (to a dose of 5 Gy per fraction) as per the investigator's discretion. The primary endpoint is the incidence of physician-reported acute grade ≥ 2 genitourinary (GU) toxicity (during the first 90 days after SBRT), as assessed by the CTCAE version 4.03 scale. Secondary clinical endpoints include incidence of acute grade ≥ 2 gastrointestinal (GI) toxicity, 5-year cumulative incidences of physician-reported late grade ≥ 2 GU and GI toxicity, temporal changes in patient-reported quality of life (QOL) outcomes, 5-year biochemical recurrence-free survival and the proportion of fractions of MRI-guided SBRT in which online adaptive radiotherapy is used.

Discussion: The MIRAGE trial is the first randomized trial comparing MRI-guided with standard CT-guided SBRT for localized PCa. The primary hypothesis is that MRI-guided SBRT will lead to an improvement in the cumulative incidence of acute grade ≥ 2 GU toxicity when compared to CT-guided SBRT. The pragmatic superiority design focused on an acute toxicity endpoint will allow an early comparison of the two technologies.

Trial Registration: Clinicaltrials.gov identifier: NCT04384770. Date of registration: May 12, 2020. https://clinicaltrials.gov/ct2/show/NCT04384770 PROTOCOL VERSION: Version 2.1, Aug 28, 2020.
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http://dx.doi.org/10.1186/s12885-021-08281-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114498PMC
May 2021

First report of Plectosphaerella cucumerina causing root rot on fennel in China.

Plant Dis 2021 May 11. Epub 2021 May 11.

Gansu Agricultural University, Plant Protection, No. 1, yingmen village, anning district, lanzhou city, gansu province, LanZhon city, Gansu, China, 7330070;

Fennel (Foeniculum vulgare Mill.) is herbaceous plant commonly cultivated for culinary and medicinal uses in China (Shi et al. 2016 ). In May 2019, disease of fennel was observed in Yumen City, Gansu Province, China (N 40°28'/E 97°05'). The incidence across the fields (about 0.23 hectare) was about 4.5%. The outer leaves of diseased fennel wilted, the rhizome changed color from brown to dark brown,necrosis and rot symptoms developed on the root. Finally, the whole plant wilted and died. When pulling up, it was easy to break the root. To identify the pathogen, 15 samples of diseased plants were collected and symptomatic rhizome tissues were surface disinfected with 0.1% HgCl solution for 30 s, rinsed in sterilized water 3 times, placed on potato dextrose agar (PDA), and incubated at 25℃ in the dark. About 7 days, hyphal tips from the tissue edge were transferred to a new PDA for purification. Three isolates obtained were named as hxa, hxb and hxc. To confirm their pathogenicity, two-month old fennel seedings planted in pots, three seedings per pot, with sterilized nutrient soil were inoculated by pouring 50 ml of conidial suspension (107 conidium/mL) produced from the three isolates. Plants inoculated with sterilized water only were included as controls. Six pots of inoculated plants were maintained in climatic cabinet / chamber (> 85% RH, 25°C). The pathogenicity tests were conducted twice. After 7 days, the plants inoculated with conidial suspension of hxa developed brown necrosis and wilt symptoms resembling those originally observed in the field, whereas the controls and the plants inoculated with the other two isolates had no symptoms. Furthermore, hxa was reisolated from rhizome of these diseased plants. The results indicated that isolate hxa was the pathogen causing root rot of fennel. The colonies of hxa on PDA were white-to-cream, slimy, mycelium appressed, aerial mycelium absent. Mycelium was hyaline, septate and formed hyphal coils. Conidiophores were solitary, hyaline, sometimes crooked or sinuous, widest at the base, gradually tapering to the apex. Conidia were smooth, hyaline, aseptate, elliptical and ovoid, measuring 5.97 to 9.51 × 2.13 to 3.58 um (avg. 7.58×2.78, n=100). These morphological characters of the fungal isolates were identical to those of Plectosphaerella cucumerina (Carlucci et al. 2012). For molecular identification, genomic DNA was extracted from the mycelium, and the rDNA internal transcribed spacer (ITS) region, portions of the 28S ribosomal RNA (LSU), calmodulin (CaM) and translation elongation factor 1α (Ef-1α) gene were amplified using primer pairs ITS1/ITS4, LROR/LR5, CMD5/CMD6 and 688f/1251R (White et al., 1990; Hopple et al., 1999; Hong et al., 2005; Alves et al., 2008), respectively. The sequences of these genes were deposited in GenBank (accessions: ITS as MW426266, LSU as MW433724, CaM as MW448071 and EF-1a as MW459981) and used in analysis to generate a phylogenetic tree. These sequences showed 100, 100, 96 and 97.32% homology to the sequences of P. cucumerina (GenBank accession no. EU594566, MH867359, KY416911 and KY964491), respectively. According to morphological characteristics and phylogenetic analysis, isolate hxa was identified as P. cucumerina. To our knowledge, this is the first report of P. cucumerina causing root rot of fennel in China as well as worldwide. This finding may help to take effective control measures of root rot on fennel.
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http://dx.doi.org/10.1094/PDIS-01-21-0166-PDNDOI Listing
May 2021

Evaluation of the Genetic Association and Methylation of Immune Response Pathway Genes with the Risk of Chronic Periodontitis in the Uighur Population.

Genet Test Mol Biomarkers 2021 May 4;25(5):317-324. Epub 2021 May 4.

Department of Endodontics, First Affiliated Hospital of Xinjiang Medical University, and College of Stomatology of Xinjiang Medical University, Urumqi, China.

The aim of this study was to explore the possible associations between single nucleotide polymorphisms (SNPs) and DNA methylation levels of seven genes in the inflammatory response pathway with susceptibility to chronic periodontitis (CP) among the Uighur population of the Xinjiang Autonomous Region of China. A total of 444 eligible subjects (279 CP patients and 165 healthy controls) were enrolled in the study. Genomic DNA was obtained from gingival tissue for genotyping eight SNPs and performing methylation measurements of seven genes. SNP in the formyl peptide receptor 1 () gene achieved statistical significance in a standard allelic association analysis for CP ( = 0.02). The frequency of the minor allele G was higher in the cases than in controls (0.367 vs. 0.291). Additionally, was significantly associated with CP under the dominant genetic model ( = 0.03). Using logistic regression analysis, was found to be consistently associated with CP under the additive dominant model, and this association remained significant after covariates were taken into account [odds ratio (OR) = 1.49 (1.09-2.05),  = 0.014; OR = 1.58 (1.04-2.40),  = 0.031, respectively]. No significant gene-gene interactions were identified. Although we did not find a polymorphism in interleukin 6 () associated with CP in our study, the methylation level of a CpG island region located within the promoter region of was significantly less in CP patients compared with controls ( < 0.05). The genetic polymorphism in and the methylation level of the promoter region of might be associated with CP in the Uighur population of China.
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http://dx.doi.org/10.1089/gtmb.2020.0334DOI Listing
May 2021

First report of Boeremia exigua var. exigua causing branch blight on walnut in China.

Plant Dis 2021 Apr 28. Epub 2021 Apr 28.

Gansu Agricultural University, College of Plant Protection, No. 1 Yingmen Village, Anning District,, Lanzhou, Gansu, China, 730070;

Walnut (Juglans sinensis L.) is an important economic tree. Its fruit are rich in omega-3 essential fatty acids, which are valuable nutritionally (Cheon et al, 2013). In March 2019, severe branch blight of walnuts (cv. Qingxiang) were observed in two fields in Ganquan Town, Gansu Province, China (N 33°56'/E105°44'). The incidence was about 3% among 10,000 walnuts. Disease symptoms included fusiform or oval black lesions gradually expanded on the branches, blight and dieback of branches, reddish brown dead branch bark with lots of black small spots (pycnidia), and defoliation. To isolate pathogen, 30 diseased tissues collected from different trees were disinfected with 0.1% HgCl solution for 1 min, rinsed in sterilized water 3 times, and placed on potato dextrose agar (PDA) at 25℃ in the dark. About three days later, 4 fungal isolates (3-3, 3-6, 3-9 and H3) with similar morphological characteristics were obtained. Their colonies, with regular margin on OA, 6.1~6.8 cm diam. after 7 days, were loose, greenish olivaceous to olivaceous grey, velvety, floccose to woolly. The conidia (n=60) were 4.77 to 8.84 μm long (mean = 6.88 μm; SD ± 0.91 μm) × 1.71 to 3.89 μm wide (mean = 2.81 μm; SD ± 0.53 μm), cylindrical, ellipsoidal to oblong, hyaline and aseptate. Pycnidia (n=25) were 76.66 ~ 132.86μm diam. (mean = 102.93 μm; SD ± 12.15 μm), variable in shape and size, mostly globose to subglobose. These characteristics were similar to B. exigua var. exigua (Boeremia et al, 2004). Pathogenicity tests of four isolates were performed 3 times on 5 healthy 2-3 years old walnuts (cv. Qingxiang). Plants were wounded by insect needle No.6 and inoculated with 5 mm mycelium block grew on PDA medium or PDA medium as control and kept moist in climatic cabinet (> 85% RH, 25°C). After 3 days, oval black lesions were occurred on branches and gradually expanded, but control was asymptomatic. And original isolates were re-isolated from these diseased shoots. Genomic DNA of four isolates were extracted, and the internal transcribed spacer (ITS), β-tubulin (tub2) and RNA polymerase II second largest subunit (rpb2) gene were amplified and sequenced using the primers ITS1/ITS4, Btub2Fd/Btub4Rd and RPB2-5F2/fRPB2-7CR (White et al, 1990; Woudenberg et al, 2009; Chen et al, 2015), respectively. Sequences were deposited in GenBank (accession no. ITS: MT154621, MT154622, MT154623, MT154624; tub2: MT223481, MT223482, MT223483, MT223484; rpb2: MW448152, MW448153, MW459982, MW459983), and compared with available sequences in NCBI. Results showed that ITS of four isolates have 100% sequence identity to Boeremia spp., tub2 and rpb2 have 100% sequence identity to B. exigua var. exigua (GenBank accession no. MN983734, MN983315) and B. exigua var. linicola (GenBank accession no. MN983785, MT920619). According to host specificity (Boeremia et al, 1976). A 106 conidium/mL spore suspension of four isolates or sterile water were inoculated on stem base of two-month old flax seedlings, placed in climatic cabinet (> 85% RH, 25°C) for moisturing and repeated three times. After two weeks, all inoculated plants still were asymptomatic, indicated that four isolates aren't B. exigua var. linicola. Therefore, they were identified as B. exigua var. exigua based on morphological characteristics, molecular analysis and pathogenicity tests. To our knowledge, this is the first report of B. exigua var. exigua causing walnut branch blight worldwide, which will provide further guidance for prevention and control of walnut branch blight.
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http://dx.doi.org/10.1094/PDIS-02-21-0382-PDNDOI Listing
April 2021

Nitrogen doped porous carbon coated antimony as high performance anode material for sodium-ion batteries.

Nanotechnology 2021 May 10;32(31). Epub 2021 May 10.

Hunan Key Lab of Mineral Materials and Application, School of Minerals Processing and Bioengineering, Central South University, Changsha 410083, People's Republic of China.

Sb holds the promise of being a high performance anode for sodium ion batteries(SIBs), while effective preparation of decent antimony(Sb) based anode materials for sodium storage is still under exploration. Herein, we propose a simple approach to achieve a high performance anode, using polyaniline as the carbon source and SbClas the metal source. Synergetic polymerization and hydrolysis reactions combined with subsequent thermal reduction endow Sb/C-PANI electrode possessing ultrafine Sb nanoparticles symmetrically distributed in the nitrogen(N) doped porous carbon matrix. The Sb/C-PANI electrode exhibits excellent sodium storage performance, featured for a high reversible capacity of 469.5 mAh gafter 100 cycles at 100 mA gand 336.5 mAh gafter 300 cycles under 500 mA g. Such impressive performance will advance the development of Sb based anode materials for sodium storage. The present approach provides a compatible strategy for preparation of anode materials with high reversible capacity and long lifespan.
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http://dx.doi.org/10.1088/1361-6528/abf778DOI Listing
May 2021

Calmodulin-Binding Protein 60b is a central transcriptional activator of immunity.

Plant Physiol 2021 Apr 12. Epub 2021 Apr 12.

State Key laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai'an, 271018, China.

Plants use a dual defense system to cope with microbial pathogens. The first involves pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) which is conferred by membrane receptors, and the second involves effector-triggered immunity (ETI), which is conferred by disease-resistance proteins (nucleotide-binding leucine-rich repeat containing proteins; NLRs). Calmodulin-Binding Protein 60 (CBP60) family transcription factors are crucial for pathogen defense: CBP60g and Systemic Acquired Resistance Deficient 1 (SARD1) positively regulate immunity, whereas CBP60a negatively regulates immunity. The roles of other Arabidopsis (Arabidopsis thaliana) CBP60s remain unclear. We report that CBP60b positively regulates immunity, and is redundant with-yet distinct from-CBP60g and SARD1. By combining ChIP-PCRs and luciferase (LUC) reporter assays, we demonstrate that CBP60b is a transcriptional activator of immunity genes. Surprisingly, CBP60b loss-of-function results in autoimmunity, exhibiting a phenotype similar to that of CBP60b gain-of-function. Mutations at the EDS1-PAD4-dependent (ENHANCED DISEASE SUSCEPTIBILITY 1- PHYTOALEXIN DEFICIENT 4) ETI pathway fully suppressed the defects of CBP60b loss-of-function but not those of CBP60b gain-of-function, suggesting that CBP60b is monitored by NLRs. Functional loss of SUPPRESSOR OF NPR1-1, CONSTITUTIVE 1 (SNC1), an R-gene, partially rescued the phenotype of cbp60b, further supporting that CBP60b is a protein targeted by pathogen effectors, i.e., a guardee. Unlike CBP60g and SARD1, CBP60b is constitutively and highly expressed in unchallenged plants. Transcriptional and genetic studies further suggest that CBP60b plays a role redundant with CBP60g and SARD1 in pathogen-induced defense, whereas CBP60b has a distinct role in basal defense, partially via direct regulation of CBP60g and SARD1.
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http://dx.doi.org/10.1093/plphys/kiab164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260125PMC
April 2021

[The Influence of Serum Homocysteine Level to the Prognosis of Newly Diagnosed Multiple Myeloma Patients and Analysis of Related Factors].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Apr;29(2):530-534

Department of Hematology,Gansu Provincial Hospital,Lanzhou 730700,Gansu

Objective: To analyze the influence of serum homocysteine (Hcy) levels to the prognosis of newly diagnosed multiple myeloma (MM) patients, and to explore related factors affecting the prognosis of the patients.

Methods: The clinical pathological data of 180 newly diagnosed MM patients treated in our hospital from March 2013 to February 2015 were collected, and the patients were divided into high and low Hcy groups based on the median Hcy. The survival curves of the patients in the two groups were drawn to compare the differences of the survival; univariate and multivariate survival analysis was used to observe the influence of serum cysteine to the prognosis of newly diagnosed MM patients; the clinicopathological data of the patients with high and low Hcy in the two groups was compared, Pearson test was used to further analyzes the relationship between Hcy and different factors, and explores the related factors of Hcy affecting the prognosis of the patients.

Results: The median survival times of patients in the high and low Hcy groups were 32 (5-59) and 41 (7-71) months, respectively. The 3-year survival rate of the patients in high Hcy group was significantly lower than those in low Hcy group, and the difference shows statistically significant (P<0.05). The results of univariate survival analysis showed that the OS of newly diagnosed MM patients whom with advanced age, high bone disease grade, high-level bone marrow plasma cell count, LDH, C-reactive protein, Cr, β-MG, Hcy, low-level Hb, and ALB was significantly shortened (all P<0.05). The results of multivariate survival analysis showed that old age, high levels of bone marrow plasma cells, Cr, β-MG, low levels of Hb, and ALB were the independent risk factors shorting the overall survival (OS) time of newly diagnosed MM patients (all P<0.05), while Hcy showed no independent relation for the OS of patients (P>0.05). The Hb level of the patients in high Hcy group was significantly lower than those in low-Hcy group, while the LDH level was significantly higher than those in low Hcy group (all P<0.05). Pearson test results showed that serum Hcy and Hb showed negative correlation (r=-0.813, P<0.05), but it shows positive correlation with LDH (r=0.726, P<0.05).

Conclusion: Serum Hcy level has a correlation trend with the survival of newly diagnosed MM, which is affected by factors such as Hb.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.02.035DOI Listing
April 2021

Walnut oil alleviates DSS-induced colitis in mice by inhibiting NLRP3 inflammasome activation and regulating gut microbiota.

Microb Pathog 2021 May 26;154:104866. Epub 2021 Mar 26.

Yunnan Academy of Forestry and Grassland, Kunming, 650204, China. Electronic address:

Ulcerative colitis (UC) has become a global disease and closely related to changes in intestinal oxidative stress, inflammatory factors and gut microbiota. Furthermore, the NLRP3 inflammasome activation is a key cause in the pathogenesis of dextran sulfate sodium (DSS)-induced colitis. Recent data showed the potential antioxidative and anti-inflammatory advantage of walnut oil, which widely used in traditional medicine and has become a dietary supplement for some patients. Therefore, we investigated whether walnut oil exerts an anti-inflammatory effect on DSS-induced colitis mice by targeting NLRP3 inflammasome and gut microbiota. Our data showed that walnut oil ameliorated the pathological morphology, decreased the reactive oxygen species (ROS) production and pro-inflammatory cytokines release, down-regulated the related gene proteins expression of NLRP3/ASC/Caspase-1 inflammatory pathway, inhibited apoptosis, shifted from more pathogens towards probiotics, and increased the levels of short-chain fatty acids (SCFAs) in DSS-induced damaging process. Collectively, our study concludes that walnut oil exerts anti-inflammatory effect on DSS-induced colitis in mice by inhibiting the NLRP3 inflammasome activation and modulating gut microbiota, and may be a prominent functional food candidate for UC treatment.
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http://dx.doi.org/10.1016/j.micpath.2021.104866DOI Listing
May 2021

Do polystyrene nanoplastics affect the toxicity of cadmium to wheat (Triticum aestivum L.)?

Environ Pollut 2020 Aug 9;263(Pt A):114498. Epub 2020 Apr 9.

MOE Key Laboratory of Pollution Processes and Environmental Criteria, Tianjin Key Laboratory of Environmental Technology for Complex Trans-Media Pollution, College of Environmental Science and Engineering, Nankai University, Tianjin, 300350, PR China. Electronic address:

There has been an increase on the research of microplastics (<5 mm in diameter) as carriers for toxic chemicals to evaluate their risks for human health and environment, but only few works focused on nanoplastics (1 nm-1000 nm in diameter) interacting with pre-existing contaminants such as heavy metals. It is still unclear whether polystyrene nanoplastics (PSNPs) could affect the toxicity of cadmium to wheat (Triticum aestivum L.). Here, we assessed the impact of polystyrene nanoplastics (0, 10 mg/L) on the Cd (0, 20 μM) toxicity to wheat grown in 25% Hoagland solution for three weeks. We found that the presence of PSNPs could partially reduce Cd contents in leaves and alleviate Cd toxicity to wheat, which might be due to weakened adsorption capacity of PSNPs affected by ionic strength. In addition, PSNPs have little effect on catalase (CAT), peroxidase (POD) activities, except for decreasing superoxide dismutase (SOD) activity, which suggested that antioxidant defense systems might not be the main mechanism to reduce the oxidative damage induced by Cd in wheat. Electron paramagnetic resonance (EPR) analysis showed that PSNPs could accelerate the formation of long-lived radicals in leaves after exposure to Cd. Notably, our metabolomics profiling further indicated that the simultaneously elevated carbohydrate and amino acid metabolisms induced by PSNPs could partly alleviate Cd toxicity to wheat. Nevertheless, the present study provides important implications for the toxicological interaction and future risk assessment of co-contamination of nanoplastics and heavy metals in the environment.
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http://dx.doi.org/10.1016/j.envpol.2020.114498DOI Listing
August 2020

An anatomical knowledge-based MRI deep learning pipeline for white matter hyperintensity quantification associated with cognitive impairment.

Comput Med Imaging Graph 2021 Apr 3;89:101873. Epub 2021 Feb 3.

School of Electronic and Information Engineering, Harbin Institute of Technology at Shenzhen, Shenzhen, Guangdong, China; Peng Cheng Laboratory, Shenzhen, Guangdong, China; National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China. Electronic address:

Recent studies have confirmed that white matter hyperintensities (WMHs) accumulated in strategic brain regions can predict cognitive impairments associated with Alzheimer's disease (AD). The knowledge of white matter anatomy facilitates lesion-symptom mapping associated with cognition, and provides important spatial information for lesion segmentation algorithms. However, deep learning-based methods in the white matter hyperintensity (WMH) segmentation realm do not take full advantage of anatomical knowledge in decision-making and lesion localization processes. In this paper, we proposed an anatomical knowledge-based MRI deep learning pipeline (U-Net), handcrafted anatomical-based spatial features developed from brain atlas were integrated with a well-designed U-Net configuration to simultaneously segment and locate WMHs. Manually annotated data from WMH segmentation challenge were used for the evaluation. We then applied this pipeline to investigate the association between WMH burden and cognition within another publicly available database. The results showed that U-Net significantly improved segmentation performance compared with methods that did not incorporate anatomical knowledge (p < 0.05), and achieved a 14-17% increase based on area under the curve (AUC) in the cohort with mild WMH burden. Different configurations for incorporating anatomical knowledge were evaluated, the proposed stage-wise U-Net-two-step method achieved the best performance (Dice: 0.86, modified Hausdorff distance: 3.06 mm), which was comparable with the state-of-the-art method (Dice: 0.87, modified Hausdorff distance: 3.62 mm). We observed different WMH accumulation patterns associated with normal aging and cognitive impairments. Furthermore, the characteristics of individual WMH lesions located in strategic regions (frontal and parietal subcortical white matter, as well as corpus callosum) were significantly correlated with cognition after adjusting for total lesion volumes. Our findings suggest that U-Net is a reliable method to segment and quantify brain WMHs in elderly cohorts, and is valuable in individual cognition evaluation.
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http://dx.doi.org/10.1016/j.compmedimag.2021.101873DOI Listing
April 2021

Identifying the Best Candidates for Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography as the Primary Staging Approach Among Men with High-risk Prostate Cancer and Negative Conventional Imaging.

Eur Urol Oncol 2021 Feb 15. Epub 2021 Feb 15.

Department of Radiation Oncology, UCLA Medical Center, Los Angeles, CA, USA. Electronic address:

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is an emerging imaging modality with greater sensitivity and specificity over conventional imaging for prostate cancer (PCa) staging. Using data from two prospective trials (NCT03368547 and NCT04050215), we explored predictors of overall upstaging (nodal and metastatic) by PSMA PET/CT among patients with cN0M0 National Comprehensive Cancer Network high-risk PCa on conventional imaging (n = 213). Overall, 21.1%, 8.9%, and 23.9% of patients experienced nodal, metastatic, and overall upstaging, respectively, without histologic confirmation. On multivariable analysis, Gleason grade group (GG) and percent positive core (PPC) on systematic biopsy significantly predict overall upstaging (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.33-3.45; p =  0.002; and OR 1.03, 95% CI 1.01-1.04; p <  0.001). Overall upstaging was significantly more frequent among men with GG 5 disease (33.0% vs. 17.6%; p =  0.0097) and PPC ≥50% (33.0% vs 15.0%; p =  0.0020). We constructed a nomogram that predicts overall upstaging using initial prostate-specific antigen, PPC, GG, and cT stage, with coefficients estimated from a standard logistic regression model (using maximum likelihood estimation). It is internally validated with a tenfold cross-validated area under the receiver operating characteristic curve estimated at 0.74 (95% CI 0.67-0.82). In our cohort, 90% of patients who had a nomogram-estimated risk below the cutoff of 22% for overall upstaging could have been spared PSMA PET/CT as our model correctly predicted no upstaging. In other words, the predictive model only missed 10% of patients who would otherwise have benefitted from PSMA PET/CT. PATIENT SUMMARY: We analyzed predictors of overall upstaging (lymph node or/and metastasis) by prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) from conventional imaging in men with high-risk prostate cancer undergoing initial staging deemed free of disease in the lymph nodes and distant metastasis by conventional imaging techniques. We found that the pathologic grade and disease burden in a prostate biopsy are associated with upstaging. We also developed a tool that predicts the probability of upstaging according to an individual patient's characteristics. Our study may help in defining patient groups who are most likely to benefit from the addition of a PSMA PET/CT scan.
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http://dx.doi.org/10.1016/j.euo.2021.01.006DOI Listing
February 2021

Cullin-RING Ligases as Promising Targets for Gastric Carcinoma Treatment.

Pharmacol Res 2021 Feb 15:105493. Epub 2021 Feb 15.

School of Pharmaceutical Sciences, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, PR China. Electronic address:

Gastric carcinoma has serious morbidity and mortality, which seriously threats human health. The studies on gastrointestinal cell biology have shown that the ubiquitination modification that occurs after protein translation plays an essential role in the pathogenesis of gastric carcinoma. Protein ubiquitination is catalyzed by E3 ubiquitin ligase and can regulate various substrate proteins in different cellular pathways. Cullin-RING E3 ligase (CRLs) is a representative of the E3 ubiquitin ligase family, which requires cullin (CUL) neddylation modification for activation to regulate homeostasis of ~20% of cellular proteins. The substrate molecules regulated by CRLs are often involved in many cell progressions such as cell cycle progression, cell apoptosis, DNA damage and repair. Given that CRLs play an important role in modulation of biological activities, so targeting a certain CULs member neddylation may be an attractive strategy for selectively controlling the cellular proteins levels to achieve the goal of cancer treatment. In this review, we will discuss the roles of CULs and Ring protein in gastric carcinoma and summarize the current neddylation modulators for gastric carcinoma treatment.
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http://dx.doi.org/10.1016/j.phrs.2021.105493DOI Listing
February 2021

Near-infrared fluorescent probe with large stokes shift for detecting Human Neutrophil elastase in living cells.

Spectrochim Acta A Mol Biomol Spectrosc 2021 May 3;252:119533. Epub 2021 Feb 3.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China. Electronic address:

Human Neutrophil elastase (HNE) plays a great role in immune responses and inflammation, and is associated closely with lung cancer and acute lung injury (ALI). Accurate detection of its activity is imperative to understand its biological function and diagnosing the disease states through monitoring the dynamic changes. Herein, we report a new NIR fluorescent probe (F-1) with large Stokes shift (182 nm). Probe F-1 featured high sensitivity (LOD ~ 5.6 ng/mL), good selectivity, low toxicity and a bright NIR emission triggered by HNE. Moreover, F-1 was successfully applied as an indicator to track the HNE in the A549 cells. Thus, F-1 may be an excellent tool for detecting enzymatic activity for preclinical applications and NE related diseases.
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http://dx.doi.org/10.1016/j.saa.2021.119533DOI Listing
May 2021

Insecticidal action of the botanical insecticide wilforine on Mythimna separata (Walker) related with the changes of ryanodine receptor expression.

Ecotoxicol Environ Saf 2021 Apr 9;213:112025. Epub 2021 Feb 9.

College of Plant Protection, Northwest A & F University, Yangling, Shaanxi Province 712100, China. Electronic address:

The detailed molecular mechanism of wilforine, a novel botanical insecticidal component, remains unclear, except for the knowledge that it affects the calcium signaling pathway. The aim of the current study was to examine the underlying molecular mechanism of wilforine in Mythimna separata (Walker) by transcriptome and RNA interference (RNAi), with chlorantraniliprole as control. RNA sequencing showed that the relative expression of genes related to the calcium signaling pathway and muscle contraction in M. separata treated with wilforine significantly changed and was further validated by qRT-PCR. Interestingly, the expression level of the ryanodine receptor (MsRyR) gene was downregulated by wilforine at relatively high concentrations and long treatment time, contrary to that observed using chlorantraniliprole. Furthermore, a putative MsRyR was cloned using a 16,258-bp contiguous sequence containing a 308-bp 5'-untranslated region and 578-bp 3'-untranslated region by RT-PCR and RACE. The results of the RNAi experiment showed that injection of dsMsRyR significantly reduced MsRyR mRNA levels, and growth and development were inhibited. Importantly, silencing of the MsRyR gene resulted in decreased susceptibility to both wilforine and chlorantraniliprole. Together with the results of our previous studies on toxic symptoms and muscle tissue lesions between wilforine and chlorantraniliprole, we propose that RyR Ca release channel dysfunction is closely related with significant lethal mechanisms of wilforine.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112025DOI Listing
April 2021