Publications by authors named "Xintong Li"

83 Publications

Non-muscle myosin heavy chain 9 maintains intestinal homeostasis by preventing epithelium necroptosis and colitis adenoma formation.

Stem Cell Reports 2021 Apr 8. Epub 2021 Apr 8.

The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China; Max-Planck Center for Tissue Stem Cell Research and Regenerative Medicine, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China. Electronic address:

Non-muscle myosin IIA plays an important role in cell adhesion, cell migration, and tissue architecture. We previously showed that low activity of the heavy chain of non-muscle myosin II Myh9 is beneficial to LGR5 intestinal stem cell maintenance. However, the function of Myh9 in adult mouse intestinal epithelium is largely unclear. In this study, we used the inducible Villin-creERT2 knockout approach to delete Myh9 in adult mouse intestinal epithelium and observed that homozygous deletion of Myh9 causes colitis-like morphologic changes in intestine, leads to a high sensitivity to dextran sulfate sodium and promotes colitis-related adenoma formation in the colon. Myh9 deletion disturbs cell junctions and impairs intestinal lumen barrier integrity, promoting the necroptosis of epithelial cells. Consistently, these changes can be partially rescued by Ripk3 knockout. Our results indicate that Myh9 is required for the maintenance of intestinal epithelium integrity and the prevention of cell necroptosis.
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http://dx.doi.org/10.1016/j.stemcr.2021.03.027DOI Listing
April 2021

A review of the synthesis of nitric oxide donor and donor derivatives with pharmacological activities.

Mini Rev Med Chem 2021 Apr 12. Epub 2021 Apr 12.

Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Harbin,150081. China.

Endogenous nitric oxide (NO) is an important effector molecule and signal transduction molecule, which participates in the regulation of multiple functions in organisms, involving a variety of physiological and pathological processes, especially playing a very important role in the cardiovascular, immune, and nervous systems. NO is a gaseous substance with a short half-life in the body and is unstable in aqueous solutions. Therefore, many researchers focus on the release and activity of NO donors and their derivatives. However, NO donors can release free NO or NO analogues under physiological conditions to meet the human need. NO donors can be coupled with the corresponding active basic nucleus, so that they have the biological activity derived from both the basic nucleus and the NO donors, thus performing better bioactivity. This paper reviewed the routes of synthesis and advance activities of NO donor derivatives.
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http://dx.doi.org/10.2174/1389557521666210412161801DOI Listing
April 2021

Psychometric properties of the Chinese version of the attitude towards the prevention of incontinence-associated dermatitis (C-APrIAD) among Chinese nurses.

J Tissue Viability 2021 Mar 28. Epub 2021 Mar 28.

School of Nursing, Peking University, Beijing, China. Electronic address:

Aim: Nurses' attitude is a significant determinant of incontinence-associated dermatitis (IAD) prevention, and a positive attitude may benefit quality improvement projects. This research aimed to translate the attitude towards the prevention of incontinence-associated dermatitis instrument (C-APrIAD) into Chinese and test the reliability and validity among Chinese nurses.

Methods: The C-APrIAD was translated into Chinese using a standard procedure of backward-forward translation and cross-cultural adaption. Totally 170 nurses were recruited through the convenience sampling method from three tertiary hospitals in Tianjin, Shandong, and Heilongjiang province of China. Reliability (internal consistency, stability) and validity (content validity, structure validity, and convergent validity), were assessed. Convergent Validity was evaluated by correlation with the General Self-Efficacy Scale (GSES).

Results: Of the 170 completed questionnaires, 158 (93%) were suitable for analysis. The item-total correlation coefficients ranged from 0.39 to 0.80. The content validity of C-APrIAD was 0.96. A factor analysis indicated the construct of a 14-item instrument in a four factors solution: (1) beliefs about the impact of IAD on patients, (2) beliefs about team responsibility to prevent IAD, (3) beliefs about personal responsibility to prevent IAD, and (4) beliefs about the effectiveness of IAD prevention products and procedures. The correlation coefficient between the GSES and C-APrIAD was 0.49 (P < 0.01). For the total instrument, the Cronbach's α coefficient was 0.87 and the test-retest reliability was 0.99.

Conclusion: The C-APrIAD is reliable and valid. The C-APrIAD may benefit nursing research as well as clinical practice to optimize interventions to improve IAD prevention.
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http://dx.doi.org/10.1016/j.jtv.2021.03.006DOI Listing
March 2021

Characterizing the incidence of adverse events of special interest for COVID-19 vaccines across eight countries: a multinational network cohort study.

medRxiv 2021 Mar 28. Epub 2021 Mar 28.

Background: As large-scale immunization programs against COVID-19 proceed around the world, safety signals will emerge that need rapid evaluation. We report population-based, age- and sex- specific background incidence rates of potential adverse events of special interest (AESI) in eight countries using thirteen databases.

Methods: This multi-national network cohort study included eight electronic medical record and five administrative claims databases from Australia, France, Germany, Japan, Netherlands, Spain, the United Kingdom, and the United States, mapped to a common data model. People observed for at least 365 days before 1 January 2017, 2018, or 2019 were included. We based study outcomes on lists published by regulators: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain-Barre syndrome, hemorrhagic and non-hemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, and transverse myelitis. We calculated incidence rates stratified by age, sex, and database. We pooled rates across databases using random effects meta-analyses. We classified meta-analytic estimates into Council of International Organizations of Medical Sciences categories: very common, common, uncommon, rare, or very rare.

Findings: We analysed 126,661,070 people. Rates varied greatly between databases and by age and sex. Some AESI (e.g., myocardial infarction, Guillain-Barre syndrome) increased with age, while others (e.g., anaphylaxis, appendicitis) were more common in young people. As a result, AESI were classified differently according to age. For example, myocardial infarction was very rare in children, rare in women aged 35-54 years, uncommon in men and women aged 55-84 years, and common in those aged ≥85 years.

Interpretation: We report robust baseline rates of prioritised AESI across 13 databases. Age, sex, and variation between databases should be considered if background AESI rates are compared to event rates observed with COVID-19 vaccines.
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http://dx.doi.org/10.1101/2021.03.25.21254315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010764PMC
March 2021

Revealing Opinions for COVID-19 Questions Using a Context Retriever, Opinion Aggregator, and Question-Answering Model: Model Development Study.

J Med Internet Res 2021 03 19;23(3):e22860. Epub 2021 Mar 19.

Department of Linguistics, The Ohio State University, Columbus, OH, United States.

Background: COVID-19 has challenged global public health because it is highly contagious and can be lethal. Numerous ongoing and recently published studies about the disease have emerged. However, the research regarding COVID-19 is largely ongoing and inconclusive.

Objective: A potential way to accelerate COVID-19 research is to use existing information gleaned from research into other viruses that belong to the coronavirus family. Our objective is to develop a natural language processing method for answering factoid questions related to COVID-19 using published articles as knowledge sources.

Methods: Given a question, first, a BM25-based context retriever model is implemented to select the most relevant passages from previously published articles. Second, for each selected context passage, an answer is obtained using a pretrained bidirectional encoder representations from transformers (BERT) question-answering model. Third, an opinion aggregator, which is a combination of a biterm topic model and k-means clustering, is applied to the task of aggregating all answers into several opinions.

Results: We applied the proposed pipeline to extract answers, opinions, and the most frequent words related to six questions from the COVID-19 Open Research Dataset Challenge. By showing the longitudinal distributions of the opinions, we uncovered the trends of opinions and popular words in the articles published in the five time periods assessed: before 1990, 1990-1999, 2000-2009, 2010-2018, and since 2019. The changes in opinions and popular words agree with several distinct characteristics and challenges of COVID-19, including a higher risk for senior people and people with pre-existing medical conditions; high contagion and rapid transmission; and a more urgent need for screening and testing. The opinions and popular words also provide additional insights for the COVID-19-related questions.

Conclusions: Compared with other methods of literature retrieval and answer generation, opinion aggregation using our method leads to more interpretable, robust, and comprehensive question-specific literature reviews. The results demonstrate the usefulness of the proposed method in answering COVID-19-related questions with main opinions and capturing the trends of research about COVID-19 and other relevant strains of coronavirus in recent years.
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http://dx.doi.org/10.2196/22860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984426PMC
March 2021

Synergistic Effect of N-Doped sp Carbon and Porous Structure in Graphene Gels toward Selective Oxidation of C-H Bond.

ACS Appl Mater Interfaces 2021 Mar 11;13(11):13087-13096. Epub 2021 Mar 11.

School of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University, Tianjin 300072, People's Republic of China.

N-doped carbon materials represent a type of metal-free catalyst for diverse organic synthetic reactions. However, single N-doped carbon materials perform insufficiently in the selective oxidation reaction of C-H bond compared with metal catalysts or multielement co-doped materials. There are a few reports on the application of three-dimensional (3D) carbon materials in such a reaction. Besides, the relationship between the well-developed porous structures, heteroatom doping, and their catalytic performance is unclear. In this study, 3D porous N-doped graphene aerogel catalysts with high activity and selectivity for the C-H bond oxidation under mild reaction conditions have been synthesized through a two-step method. Systematic studies on the dosage of N sources, pyrolysis temperature, and their influences on the catalytic performances have been evolved. Moreover, solid evidence of the synergistic effect of sp C atoms adjacent to the N atoms and porous structure promoting the performance has been provided in this work.
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http://dx.doi.org/10.1021/acsami.0c21177DOI Listing
March 2021

Validity and reliability of the Mandarin version of the Treatment Burden Questionnaire among stroke patients in Mainland China.

Fam Pract 2021 Feb 22. Epub 2021 Feb 22.

Department of Nursing, Tianjin Huanhu Hospital, Tianjin, China.

Objectives: To examine the validity and reliability of the Mandarin version of the Treatment Burden Questionnaire (TBQ) among stroke patients.

Background: Stroke patients need long-term management of symptoms and life situation, and treatment burden has recently emerged as a new concept that can influence the health outcomes during the rehabilitation process.

Methods: The convenience sampling method was used to recruit 187 cases of stroke patients in a tertiary grade hospital in Tianjin for a formal investigation. Item analysis, reliability and validity tests were carried out. The reliability test included internal consistency and test-retest reliability. And as well as content, structure and convergent validity were performed for the validity test.

Results: Of the 187 completed questionnaires, only 180 (96.3%) were suitable for analysis. According to the experts' evaluation, the I-CVI of each item was from 0.833 to 1.000, and the S-CVI was 0.967. The exploratory factor analysis yielded three-factor components with a cumulative variation of 53.054%. Convergent validity was demonstrated using measures of Morisky's Medication Adherence Scale 8 (r = -0.450, P < 0.01). All correlations between items and global scores ranged from 0.403 to 0.638. Internal consistency reliability and test-retest reliability were found to be acceptable, as indicated by a Cronbach's α of 0.824 and an intraclass correlation coefficient of 0.846, respectively.

Conclusions: The Mandarin TBQ had acceptable validity and reliability. The use of TBQ in the assessment of treatment burden of stroke survivor may benefit health resources allocation and provide tailor therapeutic interventions to construct minimally disruptive care.
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http://dx.doi.org/10.1093/fampra/cmab004DOI Listing
February 2021

Autonomous Robot for Removing Superficial Traumatic Blood.

IEEE J Transl Eng Health Med 2021;9:2600109. Epub 2021 Feb 2.

Department of NeurosurgeryXuanwu HospitalCapital Medical UniversityBeijing100053China.

: To remove blood from an incision and find the incision spot is a key task during surgery, or else over discharge of blood will endanger a patient's life. However, the repetitive manual blood removal involves plenty of workload contributing fatigue of surgeons. Thus, it is valuable to design a robotic system which can automatically remove blood on the incision surface. : In this paper, we design a robotic system to fulfill the surgical task of the blood removal. The system consists of a pair of dual cameras, a 6-DoF robotic arm, an aspirator whose handle is fixed to a robotic arm, and a pump connected to the aspirator. Further, a path-planning algorithm is designed to generate a path, which the aspirator tip should follow to remove blood. : In a group of simulating bleeding experiments on ex vivo porcine tissue, the contour of the blood region is detected, and the reconstructed spatial coordinates of the detected blood contour is obtained afterward. The BRR robot cleans thoroughly the blood running out the incision. : This study contributes the first result on designing an autonomous blood removal medical robot. The skill of the surgical blood removal operation, which is manually operated by surgeons nowadays, is alternatively grasped by the proposed BRR medical robot.
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http://dx.doi.org/10.1109/JTEHM.2021.3056618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880304PMC
February 2021

Association of Toll-Like Receptor 4 Gene Polymorphisms with Acute Aortic Dissection in a Chinese Han Population.

Biomed Res Int 2020 9;2020:8306903. Epub 2020 Dec 9.

Department of Cardiovascular Ultrasound, The First Hospital of China Medical University, Shenyang 110001, China.

Background: Inflammation may be involved in the pathogenesis of acute aortic dissection (AAD). Toll-like receptor 4 () is known to play a critical role in regulating the immune and inflammatory processes. To date, the relationship between genetic variation of and AAD is far from clear. The purpose of our study was to illustrate the relevance of polymorphisms with the susceptibility to AAD.

Methods: A total of 222 AAD patients and 222 controls were enrolled in this study. Frequency distributions of polymorphisms (rs10759932 in the promoter and rs11536889 in the 3'-untranslated region) were determined by the KASP method. Clinical parameters were acquired from subjects' medical records, and serum levels were collected from our previously published data.

Results: We found that rs10759932 polymorphism was associated with a reduced risk of AAD in the overall population (CC vs. TT: OR = 0.393, 95%CI = 0.164-0.939, = 0.036; recessive model: OR = 0.439, 95%CI = 0.196-0.984, = 0.045) and subgroup analyses stratified by sex. The GC genotype and dominant model of rs11536889 conferred a significantly higher risk of AAD compared with GG genotype in female subjects (GC vs. GG: OR = 3.382, 95%CI = 1.051-10.885, = 0.041; dominant model: OR = 3.043, 95%CI = 1.041-8.900, = 0.042). In addition, a significant interaction between the rs11536889 recessive model and dyslipidemia was observed for an increased risk of AAD ( = 0.038, OR = 15.229) after the adjustment for potential clinical covariates. We also used the false-positive report probability (FPRP) analysis to validate the significant results. Furthermore, rs11536889 polymorphism could affect the maximal aortic diameters of AAD ( = 0.037), while AAD patients carrying CC genotype of rs10759932 showed lower serum levels than TT genotype carriers ( = 0.043).

Conclusions: Our findings provide evidence for the association between polymorphisms and AAD susceptibility in a Chinese Han population, which may have some implications for understanding the role of in the pathophysiology of AAD.
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http://dx.doi.org/10.1155/2020/8306903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783515PMC
December 2020

Pathogenicity comparison of the SMPV-11 and attenuated mink enteritis virus F61 in mink.

Virus Res 2021 Mar 7;294:198294. Epub 2021 Jan 7.

Key Laboratory of Special Animal Epidemic Disease, Ministry of Agriculture, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China. Electronic address:

Mink enteritis virus (MEV) is a major pathogen inducing acute hemorrhagic enteritis in mink. This study aims to determine the pathogenicity of the isolated MEV strain (SMPV-11) compared with the attenuated MEV strain (MEV-F61) in the mink. The two MEV strains were inoculated in the two mink groups, respectively. Then the clinical symptom, hematological, serological, and histopathological change were evaluated. Our findings showed that there were differences in the clinical features and pathological changes of the SMPV-11 and MEV-F61 in the mink. It indicates that SMPV-11 is a virulent strain, and it can be the potential MEV vaccine strain in the mink.
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http://dx.doi.org/10.1016/j.virusres.2021.198294DOI Listing
March 2021

Are Nursing Home Residents With Dementia Appropriately Treated for Fracture Prevention?

J Am Med Dir Assoc 2021 Jan 13;22(1):28-35.e3. Epub 2020 Dec 13.

Division of Pharmaceutical Outcomes and Policy, University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Chapel Hill, NC, USA; Center for Health Equity Research and Promotion, Veterans Affairs (VA) Pittsburgh Healthcare System, Pittsburgh, PA, USA.

Clinicians struggle with whether to prescribe osteoporosis medications for fracture prevention for older nursing home (NH) residents with dementia, given the lack of evidence in this population. To better understand real-world clinical practice, we conducted a retrospective cohort study examining patterns of fracture prevention medication use for older NH residents with dementia and high fracture risk. Data sources included 2015-16 Medicare claims, Part D prescriptions, and Minimum Data Set (MDS) assessments. Among NH residents aged 65+ with dementia and prior fracture or high fracture risk based on the MDS FRAiL (Fracture Risk Assessment in Long-term care), we assessed medications for fracture prevention using prescription data from 1 year prior through 90 days after the first MDS assessment. Multivariable logistic regression was used to evaluate factors associated with receiving treatment. Most of the sample (n = 72,639) was >80 years (78%), female (82%), and white (88%); 63% had moderate/severe dementia and 60% had an osteoporosis diagnosis. Only 11.6% received fracture prevention medications. In adjusted analyses, treated residents were more likely to be female, Hispanic or other non-black minority, <90 years old, and newly admitted to the NH. Other associated factors included osteoporosis diagnosis, walker or wheelchair use, bone disorders (eg, Paget disease), >5 medications, steroid or proton pump inhibitor use, and regions outside of the Northeast. Resident characteristics suggestive of comorbidity burden and worsening dementia were associated with reduced likelihood of treatment. Low use of fracture prevention medications for NH residents with dementia may reflect an attempt by prescribers reconcile medication use with changing goals of care, or inappropriate underuse in patients who still have high fracture risk. Additional research is needed to help clinicians better evaluate when to use these medications in this heterogeneous and vulnerable population.
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http://dx.doi.org/10.1016/j.jamda.2020.11.019DOI Listing
January 2021

The effect of eye gaze direction on emotional mimicry: A multimodal study with electromyography and electroencephalography.

Neuroimage 2021 02 2;226:117604. Epub 2020 Dec 2.

Department of Psychology, Renmin University of China, Room 1005, D Block, Huixian Building, 59 Zhongguancun St., Haidian Dist., Beijing, 100872, China. Electronic address:

Emotional mimicry plays an important role in social interaction and is influenced by social context, especially eye gaze direction. However, the neural mechanism underlying the effect of eye gaze direction on emotional mimicry is unclear. Here, we explored how eye gaze direction influenced emotional mimicry with a combination of electromyography (EMG) and electroencephalography (EEG) techniques, which may provide a more comprehensive measure. To do this, we recorded facial EMG and scalp EEG signals simultaneously while participants observed emotional faces (happy vs. angry) with direct or averted gaze. Then, we split the EEG trials into two mimicry intensity categories (high mimicry intensity, HMI vs. low mimicry intensity, LMI) according to EMG activity. The ERP difference between HMI and LMI EEG trials revealed four ERP components (P50, P150, N200 and P300), and the effect of eye gaze direction on emotional mimicry was prominent on P300 at P7 and P8. Moreover, we also observed differences in the effect of eye gaze direction on mimicry of happy faces and angry faces, which were found on P300 at P7, as well as P150 at P7 and N200 at P7 and Pz. In short, the present study isolated the neural signals of emotional mimicry with a new multimodal method, and provided empirical neural evidence that eye gaze direction affected emotional mimicry.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117604DOI Listing
February 2021

The DIOS framework for optimizing infectious disease surveillance: Numerical methods for simulation and multi-objective optimization of surveillance network architectures.

PLoS Comput Biol 2020 12 4;16(12):e1008477. Epub 2020 Dec 4.

Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.

Infectious disease surveillance systems provide vital data for guiding disease prevention and control policies, yet the formalization of methods to optimize surveillance networks has largely been overlooked. Decisions surrounding surveillance design parameters-such as the number and placement of surveillance sites, target populations, and case definitions-are often determined by expert opinion or deference to operational considerations, without formal analysis of the influence of design parameters on surveillance objectives. Here we propose a simulation framework to guide evidence-based surveillance network design to better achieve specific surveillance goals with limited resources. We define evidence-based surveillance design as an optimization problem, acknowledging the many operational constraints under which surveillance systems operate, the many dimensions of surveillance system design, the multiple and competing goals of surveillance, and the complex and dynamic nature of disease systems. We describe an analytical framework-the Disease Surveillance Informatics Optimization and Simulation (DIOS) framework-for the identification of optimal surveillance designs through mathematical representations of disease and surveillance processes, definition of objective functions, and numerical optimization. We then apply the framework to the problem of selecting candidate sites to expand an existing surveillance network under alternative objectives of: (1) improving spatial prediction of disease prevalence at unmonitored sites; or (2) estimating the observed effect of a risk factor on disease. Results of this demonstration illustrate how optimal designs are sensitive to both surveillance goals and the underlying spatial pattern of the target disease. The findings affirm the value of designing surveillance systems through quantitative and adaptive analysis of network characteristics and performance. The framework can be applied to the design of surveillance systems tailored to setting-specific disease transmission dynamics and surveillance needs, and can yield improved understanding of tradeoffs between network architectures.
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http://dx.doi.org/10.1371/journal.pcbi.1008477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744064PMC
December 2020

2'-Fluoroarabinonucleic Acid Nanostructures as Stable Carriers for Cellular Delivery in the Strongly Acidic Environment.

ACS Appl Mater Interfaces 2020 Nov 18. Epub 2020 Nov 18.

Department of Biomedical Engineering, College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, Jiangsu 210023, China.

DNA nanotechnology is powerful in constructing programmable nanostructures with distinct dimensions, sizes, and shapes. However, natural DNA molecules are prone to nuclease degradation, thus limiting the applications of such DNA nanostructures. 2'-Fluoroarabinonucleic acid (FANA) is a chemically modified oligonucleotide with similar base pairing properties to DNA and exhibits superior physical and chemical stabilities. In this work, FANA molecules were used to construct double crossover nanostructures, and it was demonstrated that incorporation of FANA conferred nucleic acid nanostructures with increased thermal stability and stronger nuclease resistance. More importantly, FANA nanostructures were able to maintain the structural integrity in the strongly acidic environment (pH 1.2). Last, such FANA nanostructures functioned well in acting as stable carriers of small-molecule cargoes for cellular delivery in simulated gastric fluid, while the DNA counterparts were mostly degraded. Collectively, these results demonstrated that FANA self-assembly was not only a substantial complement to the structural DNA nanotechnology but also an appealing molecular tool for biomedical applications.
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http://dx.doi.org/10.1021/acsami.0c11684DOI Listing
November 2020

Role of Electrostatics in the Heterogeneous Interaction of Two-Dimensional Engineered MoS Nanosheets and Natural Clay Colloids: Influence of pH and Natural Organic Matter.

Environ Sci Technol 2021 01 10;55(2):919-929. Epub 2020 Nov 10.

Department of Civil, Architectural and Environmental Engineering, The University of Texas at Austin, Austin, Texas 78712, United States.

Few-layered molybdenum disulfide (MoS) nanosheets are poised to be at the core of low-voltage electronic device development. Upon environmental release, these two-dimensional (2D) structures can interact with abundant natural geocolloids. This study probes the role of dimensionality in modulating the aggregation behavior of 2D MoS nanosheets with plate-like geocolloids (i.e., homoionized kaolinite and montmorillonite clays). MoS nanosheets were exfoliated using an ethanol/water mixture, and aggregation kinetics were investigated with time-resolved dynamic light scattering at low monovalent salt concentrations and at three pH levels, in the presence and absence of Suwannee River humic acid (SRHA). Results indicate that pH and particle ratios are key to modulating the stability of MoS/clay systems. At pH 4, aggregation of MoS increased with increasing MoS/clay ratios and approached maximum values of 0.09 and 0.06 nm/s in the binary systems with montmorillonite and kaolinite, respectively. Electrostatic attraction facilitates heteroaggregation at pH values of 4 and 6; differences in the clay structures (i.e., face-face or face-edge aggregates) might explain the resulting MoS/clay aggregate configurations, which were probed via the evolution of particle size distribution. The presence of only 0.1 mg/L SRHA drastically suppresses the heteroaggregation propensity of MoS nanosheets with geocolloids (to less than 0.01 nm/s at all pH values tested). The high stability of these heterogeneous systems under environmentally relevant conditions can increase the likelihood for cellular uptake and long-distance transport of MoS.
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http://dx.doi.org/10.1021/acs.est.0c03580DOI Listing
January 2021

Selection of threose nucleic acid aptamers to block PD-1/PD-L1 interaction for cancer immunotherapy.

Chem Commun (Camb) 2020 Dec 6;56(93):14653-14656. Epub 2020 Nov 6.

Department of Biomedical Engineering, College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, Jiangsu 210023, China.

Threose nucleic acid (TNA) aptamers were selected in vitro to bind PD-L1 protein and inhibit its interaction with PD-1. These biologically stable TNA aptamers bound target proteins with nanomolar affinities, and effectively blocked PD-1/PD-L1 interaction in vitro. After injection into a colon cancer xenograft mouse model, the TNA aptamer N5 was specifically accumulated at the tumour site, and significantly inhibited tumour growth in vivo.
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http://dx.doi.org/10.1039/d0cc06032aDOI Listing
December 2020

A spatial hierarchical model for integrating and bias-correcting data from passive and active disease surveillance systems.

Spat Spatiotemporal Epidemiol 2020 11 10;35:100341. Epub 2020 Jun 10.

Division of Environmental Health Sciences, University of California, Berkeley, California, USA.

Disease surveillance data are important for monitoring disease burden and occurrence, and for informing a wide range of efforts to improve population health. Surveillance for infectious diseases may be conducted passively, relying on reports from healthcare facilities, or actively, involving surveys of the population at risk. Passive surveillance typically provides wide spatial coverage, but is subject to biases arising from differences in care-seeking behavior, diagnostic practices, and under-reporting. Active surveillance minimizes these biases, but is typically constrained to small areas and subpopulations due to resource limitations. Methods based on linkage of individual records between passive and active surveillance datasets provide a means to estimate and correct for the biases of each system, leveraging the size and coverage of passive surveillance and the quality of data in active surveillance. We develop a spatial Bayesian hierarchical model for bias-correcting data from both systems to yield an improved estimate of disease measures after adjusting for under-ascertainment. We apply the framework to data from a passive and an active surveillance system for pulmonary tuberculosis (PTB) in Sichuan, China, and estimate the average sensitivity of the active surveillance system at 70% (95% credible interval: 62%, 78%), and the passive system at 30% (95% CI: 24%, 35%). Passive surveillance sensitivity exhibited considerable spatial variability, and was positively associated with a site's gross domestic product per capita. Bias-corrected estimates of county-level PTB prevalence in the province in 2010 identified regions in the southeast with the highest PTB burden, yielding different geographic priorities than previous reports.
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http://dx.doi.org/10.1016/j.sste.2020.100341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704115PMC
November 2020

Aminated N-doped graphene hydrogel for long-term catalytic oxidation in strong acidic environment.

J Hazard Mater 2021 Jan 22;401:123742. Epub 2020 Aug 22.

School of Chemical Engineering and Technology, Tianjin University, Tianjin 300050, China. Electronic address:

Metal-based catalysts in advanced oxidation processes (AOPs) are not stable under strong acidic condition due to the remarkable leaching, which will also lead to a secondary pollution. In this study, an aminated N-doped graphene hydrogel (ANGH) is synthesized from graphene oxide and ethylenediamine (EDA) via an in-situ hydrothermal process. The ANGH shows a free-standing structure and has high catalytic activity especially in phenol degradation under strong-acidic condition because of a non-radical dominated mechanism determined in this process. On the large scale, a longer lifetime of ∼1700 min for ANGH is obtained under strong-acidic condition on a dynamic amplifying device, 2.9 times longer than that at neutral condition. It is proposed that amine N can be protected by hydrogen ions from being oxidized, thus leading to the better stability. Meanwhile, the active sites of ANGH can transform from N containing groups into oxygenous groups, and the deactivated material can be reutilized 10 times for rhodamine B degradation on a large scale. The ANGH synthesized facilely and could be recycled repeatedly, which is also very stable in the strong acidic environment, thus should have great potential in wastewater remediation.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123742DOI Listing
January 2021

Frontier Orbital Energy-Customized Ionomer-Based Polymer Electrolyte for High-Voltage Lithium Metal Batteries.

ACS Appl Mater Interfaces 2020 Nov 20;12(46):51374-51386. Epub 2020 Oct 20.

Qingdao Industrial Energy Storage Research Institute, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, P. R. China.

The development of gel polymer electrolytes (GPEs) is considered to be an effective strategy to drive practical applications of high-voltage lithium metal batteries (HLMBs). However, rare GPEs that can satisfy the demands of HLMBs have been developed because of the limited compatibility with lithium anodes and high-voltage cathodes simultaneously. Herein, a novel strategy for constructing polymer matrixes with a customized frontier orbital energy for GPEs is proposed. The as-investigated polymer matrix (P(CUMA-NPF))-based GPE (P(CUMA-NPF)-GPE) obtained random polymerization delivers a wide voltage window (0-5.6 V Li/Li), large lithium-ion transference number (, 0.61), and superior electrode/electrolyte interface compatibility. It is to be noted that such a of P(CUMA-NPF)-GPE, which is one of the largest among high-voltage GPEs in a fair comparison, results from the high dissociation of lithium salts and effective anion immobilization abilities of P(CUMA-NPF). Ultimately, the as-assembled HLMB delivers more enhanced cycle performance than its counterpart of commercial liquid electrolytes. It is also demonstrated that P(CUMA-NPF) can scavenge the active PF intermediate generated in the electrolyte at the anode side, thus suppressing the PF-mediated decomposition reaction of carbonates. This work will enlighten the rational structure design of GPEs for HLMBs.
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http://dx.doi.org/10.1021/acsami.0c13520DOI Listing
November 2020

Prenatal and early-life exposure to the Great Chinese Famine increased the risk of tuberculosis in adulthood across two generations.

Proc Natl Acad Sci U S A 2020 11 19;117(44):27549-27555. Epub 2020 Oct 19.

Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA 94720;

Global food security is a major driver of population health, and food system collapse may have complex and long-lasting effects on health outcomes. We examined the effect of prenatal exposure to the Great Chinese Famine (1958-1962)-the largest famine in human history-on pulmonary tuberculosis (PTB) across consecutive generations in a major center of ongoing transmission in China. We analyzed >1 million PTB cases diagnosed between 2005 and 2018 in Sichuan Province using age-period-cohort analysis and mixed-effects metaregression to estimate the effect of the famine on PTB risk in the directly affected birth cohort (F1) and their likely offspring (F2). The analysis was repeated on certain sexually transmitted and blood-borne infections (STBBI) to explore potential mechanisms of the intergenerational effects. A substantial burden of active PTB in the exposed F1 cohort and their offspring was attributable to the Great Chinese Famine, with more than 12,000 famine-attributable active PTB cases (>1.23% of all cases reported between 2005 and 2018). An interquartile range increase in famine intensity resulted in a 6.53% (95% confidence interval [CI]: 1.19-12.14%) increase in the ratio of observed to expected incidence rate (incidence rate ratio, IRR) in the absence of famine in F1, and an 8.32% (95% CI: 0.59-16.6%) increase in F2 IRR. Increased risk of STBBI was also observed in F2. Prenatal and early-life exposure to malnutrition may increase the risk of active PTB in the exposed generation and their offspring, with the intergenerational effect potentially due to both within-household transmission and increases in host susceptibility.
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http://dx.doi.org/10.1073/pnas.2008336117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959515PMC
November 2020

Rhodiola crenulata protects against Alzheimer's disease in rats: A brain lipidomics study by Fourier-transform ion cyclotron resonance mass spectrometry coupled with high-performance reversed-phase liquid chromatography and hydrophilic interaction liquid chromatography.

Rapid Commun Mass Spectrom 2021 Jan 7;35(2):e8969. Epub 2020 Nov 7.

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, China.

Rationale: Alzheimer's disease (AD) is a chronic, severe, progressive neurodegenerative disorder associated with cognitive and memory impairment that ultimately causes death. Most approved drugs can only alleviate some of the symptoms of AD, but no interventions have been found that reverse the underlying disease mechanisms. Rhodiola crenulata extract (RCE) has been reported to alleviate AD symptoms in rats. However, its underlying mechanism of action is still unclear.

Methods: A brain lipidomics study was conducted to investigate the protective effects of RCE against AD in rats to identify potential biomarkers of AD using Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) coupled with high-performance reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC). Differences in lipid metabolism profiles were evaluated using multivariate statistical analysis. Finally, the possible mechanism of action of RCE on AD was investigated by analysing metabolic pathways.

Results: The RPLCHILIC/FT-ICR MS results showed 20 lipid components with significant differences between the control and model groups. After administration of RCE, the levels of 10 lipids in AD rats tended to shift toward reference levels. The pathway analysis revealed that the protective effect of RCE against AD might be related to regulation of glycerophospholipid metabolism.

Conclusions: This study provides a novel perspective on the potential intervention mechanism of RCE in the treatment of AD.
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http://dx.doi.org/10.1002/rcm.8969DOI Listing
January 2021

Photoformation of persistent free radicals on a montmorillonite-humic acid complex simulated as particulate organic matter in an aqueous solution.

Environ Sci Process Impacts 2020 Sep;22(9):1842-1851

Dalian Ocean University, Dalian 116023, China. and Key Laboratory of Environment Controlled Aquaculture, Ministry of Education, Dalian 116023, China.

This study investigates the formation of persistent free radicals (PFRs) on particulate organic matter (POM) under irradiation in water. A montmorillonite-humic acid complex (Mnt-HA complex) was prepared to simulate POM, and the generated PFRs were detected by the electron paramagnetic resonance (EPR) technique. EPR signals with the trend of an initial increase and then a decrease were observed under irradiation for 8 days, and the g factors were in the range of 2.0034-2.0039, which indicated the generation of carbon-centered radicals with electrophilic moieties. Different concentrations and types of halophenols and transition-metal ions were respectively adsorbed on the Mnt-HA complex to probe their influence on the formation of PFRs. The amount of PFRs generated in the Mnt-HA complexes was in the order: 2-bromophenol (2-BP) > 2,4-dibromophenol (2,4-DBP) > 2,4-dichlorophenol (2,4-DCP), which implied that halogen substitution and the number of substituents in the halophenols could affect the generation of PFRs. The effects of transition-metal ions that resulted in the reduction of PFRs when adsorbed on the Mnt-HA complex were as follows: Fe3+ > Zn2+ > Cu2+ > Mn2+, and this is in agreement with their redox capacity. Analyzing the induced generation of reactive oxygen species (ROS) and electrons on POM, it is found that halophenols and transition metal ions also affected this process under irradiation. These findings indicate that the photoformation of PFRs on POM could be a source of PFRs in aqueous environments and requires further attention.
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http://dx.doi.org/10.1039/d0em00009dDOI Listing
September 2020

Serum lipidomics study reveals protective effects of Rhodiola crenulata extract on Alzheimer's disease rats.

J Chromatogr B Analyt Technol Biomed Life Sci 2020 Nov 26;1158:122346. Epub 2020 Aug 26.

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address:

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder. Rhodiola crenulata extract (RCE) has shown its protective effects on AD, however, the underlying mechanism is still unclear. In this work, serum lipidomics was conducted to reveal the action mechanism of RCE on AD by HPLC coupled with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). The animal model of AD was reproduced by intrahippocampal injection of Aβ in rats. The novel object recognition test and passive avoidance test were performed to evaluate the protective effects of RCE on AD rats. The differences of lipid metabolism profiles in rats were evaluated by multivariate statistical analysis. Then, the potential lipid biomarkers were identified and the possible mechanism of RCE on AD was elucidated by metabolic pathways analysis. As a result, twenty-eight lipids with significant differences between the control group and the model group were screened out. With the treatment of RCE, 19 lipids in AD rats showed a trend of callback to the normal levels. The results of pathway analysis indicated that the protective effects of RCE on AD might be closely related to the regulation of linoleic acid metabolism, α-linoleic acid metabolism, sphingolipid metabolism and ether lipid metabolism. In conclusion, this study provides a new perspective on the potential intervention mechanism of RCE for AD treatment.
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http://dx.doi.org/10.1016/j.jchromb.2020.122346DOI Listing
November 2020

Metformin alleviates lead-induced mitochondrial fragmentation via AMPK/Nrf2 activation in SH-SY5Y cells.

Redox Biol 2020 09 30;36:101626. Epub 2020 Jun 30.

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China. Electronic address:

As a widely acknowledged environmental pollutant, lead (Pb) exhibits neurological toxicity primarily due to the vulnerability of neural system. It is suggested that Pb could perturb mitochondrial function, triggering the following disturbance of cellular homeostasis. Here, we focused on the role of mitochondrial dynamics in Pb-induced cell damage. Pb exposure enhanced mitochondrial fragmentation and elevated p-Drp1 (s616) level in a reactive oxygen species (ROS) dependent manner, leading to cell death and energy shortage. By applying metformin, an AMP-activated protein kinase (AMPK) activator, these impairments could be alleviated via activation of AMPK, validated by experiments of pharmacological inhibition of AMPK. Further investigation confirmed that nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor managing antioxidative function, and its downstream antioxidant detoxifying enzyme were activated by metformin, resulting in the inhibition of the Pb-caused oxidative stress. Moreover, Nrf2 mediated the protection of metformin against mitochondrial fragmentation induced by Pb exposure, while knockdown of Nrf2 abrogated the protective effect. Finally, the treatment of Mdivi-1, a mitochondrial fission inhibitor, reversed Pb-triggered cell death, revealing that excessive mitochondrial fission is detrimental. To conclude, metformin could ameliorate Pb-induced mitochondrial fragmentation via antioxidative effects originated from AMPK/Nrf2 pathway activation, promoting energy supply and cell survival.
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http://dx.doi.org/10.1016/j.redox.2020.101626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334619PMC
September 2020

A simplified strategy for molecular formula determination of chemical constituents in traditional Chinese medicines based on accurate mass, A + 1 and A + 2 isotopic peaks using Fourier transform ion cyclotron resonance mass spectrometry.

Rapid Commun Mass Spectrom 2020 Dec;34(24):e8933

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, China.

Rationale: Recently, isotopic fine structures derived from Fourier transform ion cyclotron resonance mass spectrometry have been used to determine the molecular formula for unknown compounds in many complex systems. However, a simplified strategy for molecular formula determination of chemical constituents in traditional Chinese medicines (TCMs) based on accurate mass, A + 1 and A + 2 isotopic peaks is necessary.

Methods: Salviae miltiorrhizae was selected as a representative species. First, the chemical constituents were chromatographically separated and their accurate masses were obtained. The A + 1 and A + 2 isotopic peaks of all chemical constituents were then also acquired. Finally, the chemical formulae of the chemical constituents were determined.

Results: In the sample of Salviae miltiorrhizae, the formulae of 38 CHO-containing chemical constituents were quickly determined, and all chemical constituents were identified using their tandem mass spectrometric data. Moreover, the method was validated by comparison of the A + 1 and A + 2 isotopic peaks, their fragmentation patterns and the retention times of six selected standard substances.

Conclusions: The results demonstrate that the described strategy performs well for molecular formula determination of chemical constituents in TCMs. This also indicates that this method will be meaningful for the structural identification of chemical constituents of TCMs.
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http://dx.doi.org/10.1002/rcm.8933DOI Listing
December 2020

Age-related fatty infiltration of lumbar paraspinal muscles: a normative reference database study in 516 Chinese females.

Quant Imaging Med Surg 2020 Aug;10(8):1590-1601

Department of Radiology, Beijing Jishuitan Hospital, Beijing, China.

Background: Fatty infiltration, as a result of aging, is an essential biomarker of muscle degeneration. This research aimed to investigate the age-dependent change of fatty degeneration in the paraspinal muscles of healthy Chinese women. This study also explores the effect of body size on fatty infiltration of paraspinal muscles.

Methods: Cross-sectional area of paraspinal muscles (CSA) and intermuscular adipose tissue (CSA) were measured at the L3 mid-vertebral level of 516 healthy females, who underwent abdomen quantitative computed tomography (QCT) scans. Subsequently, IMAT% [CSA / (CSA + CSA)] were calculated. The relationship between basic information and measurements was evaluated using Spearman correlations. Comparisons of QCT results among different BMI subgroups in different age groups were analyzed with the Kruskal-Wallis H test and LSD, post-hoc correction. Age-related changes were calculated after the adjustment of height and weight.

Results: The mean CSA of 20-29 years group (n=69) and 70-79 years group (n=25) were 3.00 cm and 11.06 cm, respectively. While the mean CSA of 20-29 years group was 38.46 cm and 70-79 years group was 30.86 cm. The mean IMAT% difference between 20-29 years group and 70-79 years group was -18.55%. Strong, positive non-linear associations were observed between ageing and CSA, along with IMAT% (r=0.656, P<0.01; r=0.714, P<0.01). However, CSA was shown to decrease with age in a weak, negative linear fashion (r=-0.265, P<0.01). Positive relationships between BMI and CSA, CSA, along with IMAT%, were found. Significant differences were observed between obesity and normal BMI subgroup for all variables in three age groups. CSA showed a larger age-related difference compared to CSA.

Conclusions: Fatty infiltration in paraspinal muscles increased with age and BMI, while muscle loss may be associated with aging. The present study provided standardized reference data for the fatty degeneration of paraspinal muscles across the adult lifespan of Chinese females, which will play a critical role in future studies.
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http://dx.doi.org/10.21037/qims-19-835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378097PMC
August 2020

Employs a Unique Infection Strategy Targeting Peltate Glandular Trichomes of Sweetpotato () Plants.

Phytopathology 2020 Dec 4;110(12):1923-1933. Epub 2020 Nov 4.

The Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province, Jiangsu Normal University, Xuzhou 221116, Jiangsu, P.R. China.

The infection processes of BMPZ13 (BMPZ13) was elucidated on vegetative tissues of sweetpotato plants employing light and scanning electron microscopy. Vegetative tissues infected with BMPZ13 by either wounding or nonwounding inoculation methods developed typical disease symptoms, establishing black rot in stems and necrosis on buds, young leaves, and stems of sprouts, in addition to wilt on leaves and shoot cuttings, typical of vascular associated diseases. The runner hyphae of BMPZ13 formed from germinated conidia were able to directly penetrate the epidermal cuticle for initial infection and invade sweetpotato peltate glandular trichomes, specialized secretory structures to store and secrete metabolites. A two-step biotrophic phase was observed with nonwounding inoculation on leaves and stems, featuring both intercellular and intracellular invasive hyphae, with the latter found within living cells of the leaf epidermis. Subsequent to the biotrophic phase was a necrotrophic phase displaying cell death in infected leaves and veins. Additionally, this cell death was an iron-associated ferroptosis, supporting the notion that iron is involved in the necrotrophic phase of BMPZ13 infection. Significantly, we establish that employs a unique infection strategy: the targeting of peltate glandular trichomes. Collectively, our findings show that is a plant fungal pathogen with a hemibiotrophic infection style in sweetpotato vegetative tissues.
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http://dx.doi.org/10.1094/PHYTO-05-20-0165-RDOI Listing
December 2020

Brain metabolomics study for the protective effects of Rhodiola crenulata extract on Alzheimer's disease by HPLC coupled with Fourier transform-ion cyclotron resonance mass spectrometry.

J Sep Sci 2020 Aug 22;43(16):3216-3223. Epub 2020 Jun 22.

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P. R. China.

In order to investigate the protective effects of Rhodiola crenulata extract on Alzheimer's disease, a brain metabolomics study in rats was conducted by high performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry. Rat model was constructed by bilateral hippocampal injection of amyloid-β peptide and immunohistochemistry was performed to evaluate the pharmacological effect of Rhodiola crenulata extract. Multivariate statistical analysis was used to discover potential biomarkers in rat brain and related metabolic pathways analysis was conducted to elucidate the action mechanism of Rhodiola crenulata extract. As a result, a total of 19 metabolites contributing to Alzheimer's disease progress were identified and nine of them were restored to the normal levels after drug administration. Pathway analysis revealed that the protective effects of Rhodiola crenulata extract are related to the regulation of glutathione metabolism and arachidonic acid metabolism in rat brain. In conclusion, this work demonstrates that the developed metabolomics method is useful to investigate the protective effects of Rhodiola crenulata extract against Alzheimer's disease. These outcomes may further provide reliable evidence to illuminate the intervention mechanism of other traditional Chinese medicines on Alzheimer's disease.
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http://dx.doi.org/10.1002/jssc.201901314DOI Listing
August 2020

SnpHub: an easy-to-set-up web server framework for exploring large-scale genomic variation data in the post-genomic era with applications in wheat.

Gigascience 2020 06;9(6)

Key Laboratory of Crop Heterosis and Utilization, State Key Laboratory for Agrobiotechnology, Beijing Key Laboratory of Crop Genetic Improvement, China Agricultural University, Beijing 100193, China.

Background: The cost of high-throughput sequencing is rapidly decreasing, allowing researchers to investigate genomic variations across hundreds or even thousands of samples in the post-genomic era. The management and exploration of these large-scale genomic variation data require programming skills. The public genotype querying databases of many species are usually centralized and implemented independently, making them difficult to update with new data over time. Currently, there is a lack of a widely used framework for setting up user-friendly web servers to explore new genomic variation data in diverse species.

Results: Here, we present SnpHub, a Shiny/R-based server framework for retrieving, analysing, and visualizing large-scale genomic variation data that can be easily set up on any Linux server. After a pre-building process based on the provided VCF files and genome annotation files, the local server allows users to interactively access single-nucleotide polymorphisms and small insertions/deletions with annotation information by locus or gene and to define sample sets through a web page. Users can freely analyse and visualize genomic variations in heatmaps, phylogenetic trees, haplotype networks, or geographical maps. Sample-specific sequences can be accessed as replaced by detected sequence variations.

Conclusions: SnpHub can be applied to any species, and we build up a SnpHub portal website for wheat and its progenitors based on published data in recent studies. SnpHub and its tutorial are available at http://guoweilong.github.io/SnpHub/. The wheat-SnpHub-portal website can be accessed at http://wheat.cau.edu.cn/Wheat_SnpHub_Portal/.
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http://dx.doi.org/10.1093/gigascience/giaa060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274028PMC
June 2020

Human Umbilical Cord Mesenchymal Stem Cells Attenuate Abdominal Aortic Aneurysm Progression in Sprague-Dawley Rats: Implication of Vascular Smooth Muscle Cell Phenotypic Modulation.

Stem Cells Dev 2020 08 13;29(15):981-993. Epub 2020 Jul 13.

Department of Vascular Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.

Abdominal aortic aneurysm (AAA) is life-threatening, for which efficient nonsurgical treatment strategy has not been available so far. Several previous studies investigating the therapeutic effect of mesenchymal stem cells (MSCs) in AAA indicated that MSCs could inhibit aneurysmal inflammatory responses and extracellular matrix destruction, and suppress aneurysm occurrence and expansion. Vascular smooth muscle cell (VSMC) phenotypic plasticity is reported to be predisposed in AAA initiation and progression. However, little is known about the effect of MSCs on VSMC phenotypic modulation in AAA. In this study, we investigate the therapeutic efficacy of umbilical cord mesenchymal stem cells (UC-MSCs) in elastase-induced AAA model and evaluate the effect of UC-MSC on VSMC phenotypic regulation. We demonstrate that the intravenous injection of UC-MSC attenuates elastase-induced aneurysmal expansion, reduces elastin degradation and fragmentation, inhibits MMPs and TNF-α expression, and preserves and/or restores VSMC contractile phenotype in AAA. Taken together, these results highlight the therapeutic and VSMC phenotypic modulation effects of UC-MSC in AAA progression, which further indicates the potential of applying UC-MSC as an alternative treatment candidate for AAA.
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http://dx.doi.org/10.1089/scd.2020.0058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410303PMC
August 2020