Publications by authors named "Yu Meng"

575 Publications

The Micro-RNA Cargo of Extracellular Vesicles Released by Human Adipose Tissue-Derived Mesenchymal Stem Cells Is Modified by Obesity.

Front Cell Dev Biol 2021 20;9:660851. Epub 2021 May 20.

Department of Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United States.

Obesity is a chronic disease that interferes with normal repair processes, including adipose mesenchymal stem/stromal cells (ASCs) function. ASCs produce extracellular vesicles (EVs) that activate a repair program in recipient cells partly via their micro-RNA (miRNA) cargo. We hypothesized that obesity alters the miRNA expression profile of human ASC-derived EVs, limiting their capacity to repair injured cells. Human ASCs were harvested from obese and age- and gender-matched non-obese (lean) subjects during bariatric or cosmetic surgeries, respectively ( = 5 each), and their EVs isolated. Following high-throughput sequencing analysis, differentially expressed miRNAs were identified and their gene targets classified based on cellular component, molecular function, and biological process. The capacity of human lean- and obese-EVs to modulate inflammation, apoptosis, as well as mitogen-activated protein kinase (MAPK) and Wnt signaling in injured human proximal tubular epithelial (HK2) cells was evaluated . The number of EVs released from lean- and obese-ASCs was similar, but obese-EVs were smaller compared to lean-EVs. Differential expression analysis revealed 8 miRNAs upregulated (fold change > 1.4, < 0.05) and 75 downregulated (fold change < 0.7, < 0.05) in obese-EVs vs. lean-EVs. miRNAs upregulated in obese-EVs participate in regulation of NFk-B and MAPK signaling, cytoskeleton organization, and apoptosis, whereas those downregulated in obese-EVs are implicated in cell cycle, angiogenesis, and Wnt and MAPK signaling. Treatment of injured HK2 cells with obese-EVs failed to decrease inflammation, and they decreased apoptosis and MAPK signaling significantly less effectively than their lean counterparts. Obesity alters the size and miRNA cargo of human ASC-derived EVs, as well as their ability to modulate important injury pathways in recipient cells. These observations may guide development of novel strategies to improve healing and repair in obese individuals.
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http://dx.doi.org/10.3389/fcell.2021.660851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173369PMC
May 2021

Electrodeposition of (hydro)oxides for an oxygen evolution electrode.

Chem Sci 2020 Apr 20;11(39):10614-10625. Epub 2020 Apr 20.

Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), Renewable Energy Conversion and Storage Center, College of Chemistry, Nankai University Tianjin 300071 China

Electrochemical water splitting is a promising technology for hydrogen production and sustainable energy conversion, but the electrolyzers that are currently available do not have anodic electrodes that are robust enough and highly active for the oxygen evolution reaction (OER). Electrodeposition provides a feasible route for preparing freestanding OER electrodes with high active site utilization, fast mass transport and a simple fabrication process, which is highly attractive from both academic and commercial points of view. This minireview focuses on the recent electrodeposition strategies for metal (hydro)oxide design and water oxidation applications. First, the intrinsic advantages of electrodeposition in comparison with traditional technologies are introduced. Then, the unique properties and underlying principles of electrodeposited metal (hydro)oxides in the OER are unveiled. In parallel, illustrative examples of the latest advances in materials structural design, controllable synthesis, and mechanism understanding through the electrochemical synthesis of (hydro)oxides are presented. Finally, the latest representative OER mechanism and electrodeposition routes for OER catalysts are briefly overviewed. Such observations provide new insights into freestanding (hydro)oxides electrodes prepared electrodeposition, which show significant practical application potential in water splitting devices. We hope that this review will provide inspiration for researchers and stimulate the development of water splitting technology.
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http://dx.doi.org/10.1039/d0sc01532fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162381PMC
April 2020

Antidepressant-like effect and phytochemical profile of supercritical CO₂ extract from .

Pharmazie 2021 Jun;76(6):249-255

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Bei Jing, China;, Email:

is a condiment, adding much flavor in Chinese food. Also it can be used to treat depression as a Traditional Chinese Medicine (TCM). The study here aimed to evaluate the antidepressant effect between the supercritical CO₂ extract () from and the essential oil extracted by steam distillation (). And chemical compositions of were qualitatively analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and gas chromatography-mass spectrometry (GC-MS). Compared with , showed a stronger antidepressant-like effect in FST and TST mice. And it also decreased the content of monoamine oxidase (MAO) in the cerebral cortex of stressed mice. A total of 60 compounds were identified in . Among them, 28 compounds were characterized in UPLC-Q-TOF/MS analysis and all are polymethoxyflavones (PMFs). Three main compounds, 3,5,6,7,8,3',4'-heptamethoxyflavone, nobiletin and tangeretin, together account for 66.09% of the total relative peak area. 33 terpenes were identified by GC-MS analysis, such as D-limonene (12.34%), -elemene (8.86%), germacrene D (5.59%) and (Z, E)--farnesene (5.44%). Polymethoflavones and terpenes are the main constituents of responsible for its antidepressant-like effect. The study could stimulate further investigations into the antidepressant effects and mechanism of .
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http://dx.doi.org/10.1691/ph.2021.1408DOI Listing
June 2021

The effect of the synchronized multi-dimensional policies on imported COVID-19 curtailment in China.

PLoS One 2021 1;16(6):e0252224. Epub 2021 Jun 1.

School of Economics and Management, Shanghai Maritime University, Shanghai, China.

As countries are lifting restrictions and resuming international travels, the rising risk of COVID-19 importation remains concerning, given that the SARS-CoV-2 virus could be transmitted unintentionally through the global transportation network. To explore and assess the effective strategies for curtailing the epidemic risk from international importation nationwide, we evaluated "the joint prevention and control" mechanism, which made up of 19 containment policies, on how it impacted the change of medical observation and detection time from border arrival to laboratory confirmation of COVID-19 in its burst in China. Based on 1,314 epidemiological-survey cases from February 29 to May 25, 2020, we found that the synchronized approach of implementing multi-dimensional interventional policies, such as a centralized quarantine and nucleic acid testing (NAT), flight service adjustment and border closure, effectively facilitate early identification of infected case. Specifically, the implementation of the international flight service reduction was found to be associated with a reduction of the mean intervals of diagnosis from arrival to lab-confirmation by 0.44 days maximally, and the border closure was associated with a reduction of the diagnosis interval of imported cases by 0.69 days, from arrival to laboratory confirmation. The study suggests that a timely and synchronized implementation of multi-dimensional policies is compelling in preventing domestic spreading from importation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252224PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168853PMC
June 2021

Aerophilic Co-Embedded N-Doped Carbon Nanotube Arrays as Highly Efficient Cathodes for Aluminum-Air Batteries.

ACS Appl Mater Interfaces 2021 Jun 1. Epub 2021 Jun 1.

State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.

Recently, aluminum-air batteries have attracted great interest owing to their high output energy density, low cost, and feasibility to store and transport Al metal. However, the commercial application is still hindered by the lack of a high-performance air cathode, where the oxygen reduction reaction (ORR) happens, requiring fast charge transfer and mass transport at the catalyst-electrolyte-air interface. Herein, we report an aerophilic air cathode featuring both high intrinsic catalytic activity and large three-phase interface to facilitate air transport, which is prepared by growing cobalt-embedded and nitrogen-doped carbon nanotube (CoNCNT) arrays on carbon fiber paper and then modifying surface wettability with polytetrafluoroethylene solution. The optimized air electrode during the ORR shows a high onset potential of 0.95 V and fast current increase of 342.96 mA cm V, which is comparable to the commercial 20 wt % Pt/C, and has even better stability under the same conditions. Moreover, the aluminum-air battery with the aerophilic air electrode is superior to the battery with a commercial Pt/C electrode or aerophobic electrode in terms of maximum power density and long discharging durability. Bubble behavior measurement shows that aerobic wettability plays an important role in gas transport, thus controlling ORR efficiency of the air electrode. The concept of the gas-wettable electrode proves to be effective in the enhancement of oxygen reduction kinetics and would be also adapted in other gas-involved electrodes for energy-related applications.
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http://dx.doi.org/10.1021/acsami.1c00837DOI Listing
June 2021

Contrast-Enhanced CT-Based Radiomics Analysis in Predicting Lymphovascular Invasion in Esophageal Squamous Cell Carcinoma.

Front Oncol 2021 14;11:644165. Epub 2021 May 14.

Department of Computed Tomography and Magnetic Resonance, Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Objectives: To develop a radiomics model based on contrast-enhanced CT (CECT) to predict the lymphovascular invasion (LVI) in esophageal squamous cell carcinoma (ESCC) and provide decision-making support for clinicians.

Patients And Methods: This retrospective study enrolled 334 patients with surgically resected and pathologically confirmed ESCC, including 96 patients with LVI and 238 patients without LVI. All enrolled patients were randomly divided into a training cohort and a testing cohort at a ratio of 7:3, with the training cohort containing 234 patients (68 patients with LVI and 166 without LVI) and the testing cohort containing 100 patients (28 patients with LVI and 72 without LVI). All patients underwent preoperative CECT scans within 2 weeks before operation. Quantitative radiomics features were extracted from CECT images, and the least absolute shrinkage and selection operator (LASSO) method was applied to select radiomics features. Logistic regression (Logistic), support vector machine (SVM), and decision tree (Tree) methods were separately used to establish radiomics models to predict the LVI status in ESCC, and the best model was selected to calculate Radscore, which combined with two clinical CT predictors to build a combined model. The clinical model was also developed by using logistic regression. The receiver characteristic curve (ROC) and decision curve (DCA) analysis were used to evaluate the model performance in predicting the LVI status in ESCC.

Results: In the radiomics model, Sphericity and gray-level non-uniformity (GLNU) were the most significant radiomics features for predicting LVI. In the clinical model, the maximum tumor thickness based on CECT (cThick) in patients with LVI was significantly greater than that in patients without LVI (P<0.001). Patients with LVI had higher clinical N stage based on CECT (cN stage) than patients without LVI (<0.001). The ROC analysis showed that both the radiomics model (AUC values were 0.847 and 0.826 in the training and testing cohort, respectively) and the combined model (0.876 and 0.867, respectively) performed better than the clinical model (0.775 and 0.798, respectively), with the combined model exhibiting the best performance.

Conclusions: The combined model incorporating radiomics features and clinical CT predictors may potentially predict the LVI status in ESCC and provide support for clinical treatment decisions.
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http://dx.doi.org/10.3389/fonc.2021.644165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162215PMC
May 2021

One-Cell Metabolic Phenotyping and Sequencing of Soil Microbiome by Raman-Activated Gravity-Driven Encapsulation (RAGE).

mSystems 2021 May 27:e0018121. Epub 2021 May 27.

Single-Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Institute of Energy Research, Qingdao Institute of BioEnergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China.

Soil harbors arguably the most metabolically and genetically heterogeneous microbiomes on Earth, yet establishing the link between metabolic functions and genome at the precisely one-cell level has been difficult. Here, for mock microbial communities and then for soil microbiota, we established a Raman-activated gravity-driven single-cell encapsulation and sequencing (RAGE-Seq) platform, which identifies, sorts, and sequences precisely one bacterial cell via its anabolic (incorporating D from heavy water) and physiological (carotenoid-containing) functions. We showed that (i) metabolically active cells from numerically rare soil taxa, such as spp., spp., spp., spp., and Pseudomonas spp., can be readily identified and sorted based on DO uptake, and their one-cell genome coverage can reach ∼93% to allow high-quality genome-wide metabolic reconstruction; (ii) similarly, carotenoid-containing cells such as spp., spp., spp., Pseudomonas spp., and spp. were identified and one-cell genomes were generated for tracing the carotenoid-synthetic pathways; and (iii) carotenoid-producing cells can be either metabolically active or inert, suggesting culture-based approaches can miss many such cells. As a Raman-activated cell sorter (RACS) family member that can establish a metabolism-genome link at exactly one-cell resolution from soil, RAGE-Seq can help to precisely pinpoint "who is doing what" in complex ecosystems. Soil is home to an enormous and complex microbiome that features arguably the highest genomic diversity and metabolic heterogeneity of cells on Earth. Their metabolic activities drive many natural processes of pivotal ecological significance or underlie industrial production of numerous valuable bioactivities. However, pinpointing "who is doing what" in a soil microbiome, which consists of mainly yet-to-be-cultured species, has remained a major challenge. Here, for soil microbiota, we established a Raman-activated gravity-driven single-cell encapsulation and sequencing (RAGE-Seq) method, which identifies, sorts, and sequences at the resolution of precisely one microbial cell via its catabolic and anabolic functions. As a Raman-activated cell sorter (RACS) family member that can establish a metabolism-genome link at one-cell resolution from soil, RAGE-Seq can help to precisely pinpoint "who is doing what" in complex ecosystems.
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http://dx.doi.org/10.1128/mSystems.00181-21DOI Listing
May 2021

Barbadin potentiates long-term effects of lorcaserin on POMC neurons and weight loss.

J Neurosci 2021 May 24. Epub 2021 May 24.

Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030

Obesity is a serious global health problem due to its increasing prevalence and comorbidities, but its treatments are limited. The serotonin 2C receptor (5-HTR), a G protein-coupled receptor, activates pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of hypothalamus (ARH) to reduce appetite and weight gain. However, several 5-HT analogs targeting this receptor, e.g. lorcaserin, suffer from diminished efficacy to reduce weight after prolonged administration. Here we show that barbadin, a novel β-arrestin/β2-adaptin inhibitor, can prevent 5-HTR internalization in cells and potentiate long-term effects of lorcaserin to reduce appetite and body weight in male mice. Mechanistically, we demonstrate that barbadin co-treatment can effectively maintain the sensitivity of the 5-HTR in POMC neurons, despite prolonged lorcaserin exposure, thereby allowing these neurons to be activated through opening the transient receptor potential cation channels. Thus, our results prove the concept that inhibition of 5-HTR desensitization can be a valid strategy to improve the long-term weight loss effects of lorcaserin or other 5-HTR agonists, and also provide an intellectual framework to develop effective long-term management of weight by targeting 5-HTR desensitization.By demonstrating that the combination of barbadin with a GPCR agonist can provide prolonged weight-lowering benefits in a preclinical setting, our work should call for additional efforts to validate barbadin as a safe and effective medicine or to use barbadin as a lead compound to develop more suitable compounds for obesity treatment. These results prove the concept that inhibition of 5-HTR desensitization can be a valid strategy to improve the long-term weight loss effects of lorcaserin or other 5-HTR agonists. Since GPCRs represent a major category as therapeutic targets for various human diseases and desensitization of GPCRs is a common issue, our work may provide a conceptual framework to enhance effects of a broad range of GPCR medicines.
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http://dx.doi.org/10.1523/JNEUROSCI.3210-20.2021DOI Listing
May 2021

Prenatal exposure to organophosphate esters and neonatal thyroid-stimulating hormone levels: A birth cohort study in Wuhan, China.

Environ Int 2021 May 18;156:106640. Epub 2021 May 18.

State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, Hubei 430030, China. Electronic address:

Background: Increasing animal studies have indicated that organophosphate esters (OPEs) have endocrine-disruptive potential. However, human epidemiological evidence is limited, especially in susceptible populations, such as pregnant women and neonates. The purpose of this present study was to examine the trimester-specific relationships of prenatal exposure to OPEs with neonatal thyroid-stimulating hormone (TSH).

Method: A total of 102 mother-newborn pairs were recruited from a birth cohort study between April 2015 and September 2016 in Wuhan, China. Eight OPE metabolites were detectable in urine samples from pregnant women across the different three trimesters. Neonatal TSH levels were measured using time-resolved immunofluorescence assay. The associations between maternal urinary OPE metabolites and neonatal TSH and the critical exposure windows of fetal vulnerability were estimated using multiple informant models.

Results: Seven OPE metabolites with detection frequency > 50% (52.9%-98.0%) were detected in repeated urine samples from different three trimesters, and the urinary OPE metabolites across pregnancy was of high variability (ICCs: 0.09-0.26). After adjusted for confounders (e.g., maternal age, prepregnancy BMI, passive smoking during pregnancy), some suggestive associations were observed between maternal urinary OPE metabolites and neonatal TSH in different trimesters. A doubling of second trimester di-o-cresyl phosphate & di-p-cresyl phosphate (DoCP & DpCP) was associated with a 7.82% increase in neonatal TSH level (95% CI: -0.70%, 17.06%, p-value = 0.07), a doubling of third trimester diphenyl phosphate (DPHP) was associated with a 4.71% decrease in neonatal TSH level (95% CI: -9.80%, 0.67%, p-value = 0.09), and a doubling of third trimester bis(2-butoxyethyl) phosphate (BBOEP) was associated with a 6.38% increase in neonatal TSH level (95% CI: -0.12%, 13.31%, p = 0.05). However, such associations did not differ materially across trimesters. When performing stratified analysis by infant sex, the associations were statistically significant and were sex-dependent.In females, maternal urinary DoCP & DpCP concentrations in each trimester were associated with increased neonatal TSH levels, and urinary DPHP concentration in the third trimester was associated with decreased neonatal TSH level. In males, maternal urinary BBOEP concentration in the first trimester was positively related to neonatal TSH level.

Conclusion: This prospective study demonstrated that prenatal exposure to OPEs can lead to a sex-dependent change in neonatal TSH levels. Although the sex-selective effect was differed among various urinary OPE metabolites, more evidence was supported that OPE exposure was related to increased TSH levels for both males and females.
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http://dx.doi.org/10.1016/j.envint.2021.106640DOI Listing
May 2021

Highly Dispersive Cerium Atoms on Carbon Nanowires as Oxygen Reduction Reaction Electrocatalysts for Zn-Air Batteries.

Nano Lett 2021 May 17;21(10):4508-4515. Epub 2021 May 17.

Fok Ying Tung Research Institute, Hong Kong University of Science and Technology, Guangzhou 511458, China.

Highly efficient noble-metal-free electrocatalysts for oxygen reduction reaction (ORR) are essential to reduce the costs of fuel cells and metal-air batteries. Herein, a single-atom Ce-N-C catalyst, constructed of atomically dispersed Ce anchored on N-doped porous carbon nanowires, is proposed to boost the ORR. This catalyst has a high Ce content of 8.55 wt % and a high activity with ORR half-wave potentials of 0.88 V in alkaline media and 0.75 V in acidic electrolytes, which are comparable to widely studied Fe-N-C catalysts. A Zn-air battery based on this material shows excellent performance and durability. Density functional theory calculations reveal that atomically dispersed Ce with adsorbed hydroxyl species (OH) can significantly reduce the energy barrier of the rate-determining step resulting in an improved ORR activity.
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http://dx.doi.org/10.1021/acs.nanolett.1c01493DOI Listing
May 2021

The phosphorylation of phosphoglucosamine mutase GlmM by Ser/Thr kinase STK mediates cell wall synthesis and virulence in Streptococcus suis serotype 2.

Vet Microbiol 2021 Jul 6;258:109102. Epub 2021 May 6.

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China. Electronic address:

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that causes serious economic losses in the pig industry. Phosphorylation is an important mechanism of protein modification. Recent studies have reported that the serine/threonine kinase (STK) gene contributes to the growth and virulence of SS2. However, the mechanism underlying the regulatory functions of STK in SS2 has not been thoroughly elucidated to date. In this study, phosphoproteomic analysis was performed to determine substrates of the STK protein. Twenty-two proteins with different cell functions were identified as potential substrates of STK. Phosphoglucosamine mutase (GlmM) was selected for further investigation among them. In vitro phosphorylation assay and immunoprecipitation assay indicated that GlmM was phosphorylated by STK at the Ser-101 site and the phosphorylation level of GlmM can be affected. We observed that compared to the wild-type strain ZY05719, the glmM-deficient strain (ΔglmM) and the glmM S101A point mutation strain (CΔglmM S101A) showed aberrant cell morphology and attenuated virulence, including enlarged cell volume, absent capsule, decreased resistance, lower survival caused by unusual peptidoglycan synthesis, and significantly attenuated pathogenicity in a mouse infection model. Additionally, compared to ZY05719 and CΔglmM, GlmM enzyme acivities and peptidoglycan concentrations of the stk-deficient strain (Δstk), CΔglmM S101A decreased significantly. These experiments revealed that STK phosphorylates GlmM at the Ser-101 site to impact GlmM enzyme activity and control cell wall peptidoglycan synthesis to affect SS2 pathogenicity.
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http://dx.doi.org/10.1016/j.vetmic.2021.109102DOI Listing
July 2021

Photonic Implementation of Quantum Information Masking.

Phys Rev Lett 2021 Apr;126(17):170505

CAS Key Laboratory of Quantum Information, University of Science and Technology of China, Hefei 230026, People's Republic of China.

Masking of quantum information spreads it over nonlocal correlations and hides it from the subsystems. It is known that no operation can simultaneously mask all pure states [Phys. Rev. Lett. 120, 230501 (2018)PRLTAO0031-900710.1103/PhysRevLett.120.230501], so in what sense is quantum information masking useful? Here, we extend the definition of quantum information masking to general mixed states, and show that the resource of maskable quantum states is far more abundant than the no-go theorem seemingly suggests. Geometrically, the simultaneously maskable states lays on hyperdisks in the state hypersphere, and strictly contains the broadcastable states. We devise a photonic quantum information masking machine using time-correlated photons to experimentally investigate the properties of qubit masking, and demonstrate the transfer of quantum information into bipartite correlations and its faithful retrieval. The versatile masking machine has decent extensibility, and may be applicable to quantum secret sharing and fault-tolerant quantum communication. Our results provide some insights on the comprehension and potential application of quantum information masking.
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http://dx.doi.org/10.1103/PhysRevLett.126.170505DOI Listing
April 2021

Metabolic classification of bladder cancer based on multi-omics integrated analysis to predict patient prognosis and treatment response.

J Transl Med 2021 05 13;19(1):205. Epub 2021 May 13.

Department of Urology, The First Hospital of China Medical University, Shenyang, 110001, Liaoning Province, China.

Background: Currently, no molecular classification is established for bladder cancer based on metabolic characteristics. Therefore, we conducted a comprehensive analysis of bladder cancer metabolism-related genes using multiple publicly available datasets and aimed to identify subtypes according to distinctive metabolic characteristics.

Methods: RNA-sequencing data of The Cancer Genome Atlas were subjected to non-negative matrix fractionation to classify bladder cancer according to metabolism-related gene expression; Gene Expression Omnibus and ArrayExpress datasets were used as validation cohorts. The sensitivity of metabolic types to predicted immunotherapy and chemotherapy was assessed. Kaplan-Meier curves were plotted to assess patient survival. Differentially expressed genes between subtypes were identified using edgeR. The differences among identified subtypes were compared using the Kruskal-Wallis non-parametric test. To better clarify the subtypes of bladder cancer, their relationship with clinical characteristics was examined using the Fisher's test. We also constructed a risk prediction model using the random survival forest method to analyze right-censored survival data based on key metabolic genes. To identify genes of prognostic significance, univariate Cox regression, lasso analysis, and multivariate regression were performed sequentially.

Results: Three bladder cancer subtypes were identified according to the expression of metabolism-related genes. The M1 subtype was characterized by high metabolic activity, low immunogenicity, and better prognosis. M2 exhibited moderate metabolic activity, high immunogenicity, and the worst prognosis. M3 was associated with low metabolic activity, low immunogenicity, and poor prognosis. M1 showed the best predicted response to immunotherapy, whereas patients with M1 were predicted to be the least sensitive to cisplatin. By contrast, M2 showed the worst predicted response to immunotherapy but was predicted to be more sensitive to cisplatin, doxorubicin, and other first-line anticancer drugs. M3 was the most sensitive to gemcitabine. The risk model based on metabolic genes effectively predicted the prognosis of bladder cancer patients.

Conclusions: Metabolic classification of bladder cancer has potential clinical value and therapeutic feasibility by inhibiting the associated pathways. This classification can provide valuable insights for developing precise bladder cancer treatment.
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http://dx.doi.org/10.1186/s12967-021-02865-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117567PMC
May 2021

Plant multiscale networks: charting plant connectivity by multi-level analysis and imaging techniques.

Sci China Life Sci 2021 Mar 12. Epub 2021 Mar 12.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing, 100083, China.

In multicellular and even single-celled organisms, individual components are interconnected at multiscale levels to produce enormously complex biological networks that help these systems maintain homeostasis for development and environmental adaptation. Systems biology studies initially adopted network analysis to explore how relationships between individual components give rise to complex biological processes. Network analysis has been applied to dissect the complex connectivity of mammalian brains across different scales in time and space in The Human Brain Project. In plant science, network analysis has similarly been applied to study the connectivity of plant components at the molecular, subcellular, cellular, organic, and organism levels. Analysis of these multiscale networks contributes to our understanding of how genotype determines phenotype. In this review, we summarized the theoretical framework of plant multiscale networks and introduced studies investigating plant networks by various experimental and computational modalities. We next discussed the currently available analytic methodologies and multi-level imaging techniques used to map multiscale networks in plants. Finally, we highlighted some of the technical challenges and key questions remaining to be addressed in this emerging field.
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http://dx.doi.org/10.1007/s11427-020-1910-1DOI Listing
March 2021

Control Analysis of Protein-Protein Interaction Network Reveals Potential Regulatory Targets for MYCN.

Front Oncol 2021 21;11:633579. Epub 2021 Apr 21.

Department of Physiology, Shenyang Medical College, Shenyang, China.

Background: MYCN is an oncogenic transcription factor of the MYC family and plays an important role in the formation of tissues and organs during development before birth. Due to the difficulty in drugging MYCN directly, revealing the molecules in MYCN regulatory networks will help to identify effective therapeutic targets.

Methods: We utilized network controllability theory, a recent developed powerful tool, to identify the potential drug target around MYCN based on Protein-Protein interaction network of MYCN. First, we constructed a Protein-Protein interaction network of MYCN based on public databases. Second, network control analysis was applied on network to identify driver genes and indispensable genes of the MYCN regulatory network. Finally, we developed a novel integrated approach to identify potential drug targets for regulating the function of the MYCN regulatory network.

Results: We constructed an MYCN regulatory network that has 79 genes and 129 interactions. Based on network controllability theory, we analyzed driver genes which capable to fully control the network. We found 10 indispensable genes whose alternation will significantly change the regulatory pathways of the MYCN network. We evaluated the stability and correlation analysis of these genes and found EGFR may be the potential drug target which closely associated with MYCN.

Conclusion: Together, our findings indicate that EGFR plays an important role in the regulatory network and pathways of MYCN and therefore may represent an attractive therapeutic target for cancer treatment.
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http://dx.doi.org/10.3389/fonc.2021.633579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096904PMC
April 2021

Increase of a Fibrinolytic Enzyme Production through Promoter Replacement of from CH3-5.

J Microbiol Biotechnol 2021 May 7;31(1). Epub 2021 May 7.

Division of Applied Life Science (BK21 plus), Graduate school, Jinju 52828, Korea.

CH3-5 isolated from cheonggukjang secretes a 28 kDa protease with a strong fibrinolytic activity. Its gene, , was cloned and expressed in a heterologous host (Jeong ., 2007). In this study, the promoter of was replaced with other stronger promoters (P, P, P, P) of spp. using PCR. The constructed chimeric genes were cloned into pHY300PLK vector, and then introduced into WB600. The P10 promoter conferred the highest fibrinolytic activity, i.e., 1.7-fold higher than that conferred by the original promoter. Overproduction of the 28 kDa protease was confirmed using SDS-PAGE and fibrin zymography. RT-qPCR analysis showed that expression was 2.0-fold higher with the P10 promoter than with the original promoter. Change of the initiation codon from GTG to ATG further increased the fibrinolytic activity. The highest expression was observed when two copies of the P promoter were placed in tandem upstream of the ATG initiation codon. The construct with P10 promoter and ATG and the construct with two copies of P10 promoter in tandem and ATG exhibited 117% and 148% higher fibrinolytic activity, respectively, than that exhibited by the construct containing P10 promoter and GTG. These results confirmed that significant overproduction of a fibrinolytic enzyme can be achieved by suitable promoter modification, and this approach may have applications in the industrial production of AprE3-5 and related fibrinolytic enzymes.
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http://dx.doi.org/10.4014/jmb.2103.03027DOI Listing
May 2021

Cell Wall and Hormone Interplay Controls Growth Asymmetry.

Trends Plant Sci 2021 Jul 3;26(7):665-667. Epub 2021 May 3.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China. Electronic address:

Plant cell elongation and expansion require the biosynthesis and remodeling of cell wall composition. Recently, Aryal et al. reported how feedback between the cell wall and the auxin response controls differential growth in apical hook development.
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http://dx.doi.org/10.1016/j.tplants.2021.04.003DOI Listing
July 2021

GGC repeat expansions in NOTCH2NLC causing a phenotype of distal motor neuropathy and myopathy.

Ann Clin Transl Neurol 2021 Jun 4;8(6):1330-1342. Epub 2021 May 4.

Department of Neurology, Peking University First Hospital, Beijing, 100034, China.

Background: The expansion of GGC repeat in the 5' untranslated region of the NOTCH2NLC has been associated with various neurogenerative disorders of the central nervous system and, more recently, oculopharyngodistal myopathy. This study aimed to report patients with distal weakness with both neuropathic and myopathic features on electrophysiology and pathology who present GGC repeat expansions in the NOTCH2NLC.

Methods: Whole-exome sequencing (WES) and long-read sequencing were implemented to identify the candidate genes. In addition, the available clinical data and the pathological changes associated with peripheral nerve and muscle biopsies were reviewed and studied.

Results: We identified and validated GGC repeat expansions of NOTCH2NLC in three unrelated patients who presented with progressive weakness predominantly affecting distal lower limb muscles, following negative results in an initial WES. We found intranuclear inclusions with multiple proteins deposits in the nuclei of both myofibers and Schwann cells. The clinical features of these patients are compatible with the diagnosis of distal motor neuropathy and rimmed vacuolar myopathy.

Interpretation: These phenotypes enrich the class of features associated with NOTCH2NLC-related repeat expansion disorders (NRED), and provide further evidence that the neurological symptoms of NRED include not only brain, spinal cord, and peripheral nerves damage, but also myopathy, and that overlapping symptoms might exist.
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http://dx.doi.org/10.1002/acn3.51371DOI Listing
June 2021

Construction of flood loss function for cities lacking disaster data based on three-dimensional (object-function-array) data processing.

Sci Total Environ 2021 Jun 5;773:145649. Epub 2021 Feb 5.

School of Water Conservancy Engineering, Zhengzhou University, Zhengzhou, Henan 450001, PR China.

Reliable loss estimation is crucial for flood risk management. As the current standard form of flood loss assessment, it is difficult to fit the Flood Inundated Depth-Loss Rate Function (FILF) due to the lack of historical data in most inland arid and semi-arid plain cities. To address the current trend of increasing flood risk, it has become increasingly important to develop a scientific and reasonable loss assessment function or model for these cities. Therefore, the flood loss rate data of several cities were transferred through amplified characteristic indices to form a loss rate transfer vector of cities lacking disaster data based on the analogy principle. Three-dimensional data processing rules were then set, including the priority sequence of object dimensional variance and the greatest correlation coefficient (CC) of the joint dimension of function and array. Finally, a FILF of cities lacking disaster data was constructed after three-level optimization. The FILF of eight property types was calculated taking Zhengzhou City, China, as the study area. The optimal function and array dimensions were F (Biquadratic) and D-D, respectively. All CCs exceeded 0.9935, with an average of 0.9971. The joint fitting results also showed that the function dimension was more sensitive to the FILF than the array dimension. The simulated total flood loss of the Jinshui District in 20 years was 2.46 billion yuan, and there was clear spatial disparity in economic loss. This study is expected to resolve the problem of the absence of a loss function in cities or regions lacking data to support urban flood risk management.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145649DOI Listing
June 2021

Expression levels and activation status of Yap splicing isoforms determine self-renewal and differentiation potential of embryonic stem cells.

Stem Cells 2021 May 2. Epub 2021 May 2.

Laboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing, People's Republic of China.

Yap is the key effector of Hippo signaling; however, its role in embryonic stem cells (ESCs) remains controversial. Here, we identify two Yap splicing isoforms (Yap472 and Yap488), which show equal expression levels but heterogeneous distribution in ESCs. Knockout (KO) of both isoforms reduces ESC self-renewal, accelerates pluripotency exit but arrests terminal differentiation, while overexpression of each isoform leads to the reverse phenotype. The effect of both Yap isoforms on self-renewal is Teads-dependent and mediated by c-Myc. Nonetheless, different isoforms are found to affect overlapping yet distinct genes, and confer different developmental potential to Yap-KO cells, with Yap472 exerting a more pronounced biological effect and being more essential for neuroectoderm differentiation. Constitutive activation of Yaps, particularly Yap472, dramatically upregulates p53 and Cdx2, inducing trophectoderm trans-differentiation even under self-renewal conditions. These findings reveal the combined roles of different Yap splicing isoforms and mechanisms in regulating self-renewal efficiency and differentiation potential of ESCs.
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http://dx.doi.org/10.1002/stem.3389DOI Listing
May 2021

Remarkable Phytochemical Characteristics of Chi-Nan Agarwood Induced from New-Found Chi-Nan Germplasm of Compared with Ordinary Agarwood.

Int J Anal Chem 2021 10;2021:5593730. Epub 2021 Apr 10.

Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education & National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.

Wild Chi-Nan agarwood is regarded as the highest quality agarwood from spp. However, the comprehensive research on chemical composition of wild Chi-Nan agarwood is limited. An integrated strategy using SHS-GC-MS and UPLC-Q/Tof-MS was applied to explore the phytochemical characteristics of a kind of agarwood induced from a newly identified germplasm of Chi-Nan Progenesis QI and MS-Dial were used to preprocess the UPLC-Q/Tof-MS and GC-MS raw data, respectively. Principle component analysis (PCA) and orthogonal partial least squares to latent structure-discriminant analysis (OPLS-DA) models were built to discriminate Chi-Nan agarwood from ordinary agarwood and to screen potential distinguishing components between them. In this study, we clarified the distinguishing differences between Chi-Nan agarwood and ordinary agarwood. The difference is mainly manifested in the average contents of 2-(2-phenylethyl)chromone and 2-[2-(4'-methoxybenzene)ethyl]chromone, which are 170 and 420 times higher in Chi-Nan agarwood than in ordinary agarwood, respectively, while the contents of 5,6,7,8-diepoxy-2-(2-phenylethyl)chromones(DEPECs), 5,6-epoxy-2-(2-phenylethyl)chromones(EPECs), and 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones(THPECs) such as agarotetrol are extremely low. The content of the main sesquiterpenes in Chi-Nan agarwood was higher than that in ordinary agarwood, especially in regard to guaiane and eudesmane derivatives. In addition, there were significant differences in the contents of low-molecular-weight aromatic compounds such as 2-methyl-4H-1-benzopyran-4-one, 4-methoxybenzaldehyde, and 2-hydroxybenzaldehyde between Chi-Nan agarwood and ordinary agarwood. All the mentioned main chemical characteristics of this new Chi-Nan agarwood were coincident with those of the rare wild Chi-Nan agarwood from , , and . We reported differences in 2-(2-phenylethyl)chromones, sesquiterpenes, and low-molecular-weight aromatic compounds between Chi-Nan agarwood and ordinary agarwood from for the first time; it is necessary to evaluate the agarwood from the new-found Chi-Nan germplasm.
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http://dx.doi.org/10.1155/2021/5593730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053051PMC
April 2021

Bioactive-guided isolation and identification of oligostilbenes as anti-rheumatoid arthritis constituents from the roots of Caragana stenophylla.

J Ethnopharmacol 2021 Apr 19:114134. Epub 2021 Apr 19.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China. Electronic address:

Ethnopharmacological Relevance: The roots of Caragana stenophylla have been used as folk medicine due to the functions of activating blood, diuresis, analgesic and tonicity, especially in treating rheumatoid arthritis and hypertension. However, the anti-rheumatoid arthritis mechanisms and bioactive ingredients have not previously been fully investigated.

Aim Of The Study: The aim of this study was to assess the anti-rheumatoid arthritis effects of the roots of Caragana stenophylla ethanol extract (EC), elucidate its mechanism of action and identify its active substances.

Materials And Methods: Anti-arthritic activity of EC was assessed using type II-collagen induced arthritis in rats. Arthritis severity was evaluated by foot paw volume, arthritis index, joint swelling degree and histopathology. The serum inflammatory cytokines and matrix metalloproteinases (MMPs) were also detected by immunohistochemical analysis. In addition, the protein expression of IκB, p-IκB, iNOS and COX-2 was analyzed by western blot. RAW 264.7 macrophage cells were employed to assess the anti-inflammatory effects of fractions and compounds in vitro. UPLC-Q-TOF-MS was adopted to appraise the ingredients of the active fraction of the roots of C. stenophylla. Furthermore, various chromatographic techniques and spectroscopic methods were used for isolation and structure elucidation of compounds.

Results: The results showed that EC could reduce type II collagen-induced rheumatoid arthritis model arthritic score and histopathology markedly at dose of 240 mg/kg. Besides, EC could suppress the levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17, and TNF-α) and matrix metalloproteinases (MMP-3, MMP-9), and the expression levels of COX-2, p-IκB and iNOS also were declined. While, the levels of IL-10 and IκB were increased. The ethyl acetate fraction exhibited potent inhibitory effects against nitric oxide production in RAW 264.7 macrophage cells. Eleven main components including 1 flavonoid and 10 oligostilbenes from active fraction were isolated by mass directed chromatographic techniques. Their structures were determined on the basis of various spectroscopic methods and by comparison with the published NMR data.

Conclusion: The roots of C. stenophylla attenuated arthritis severity, restored serum cytokine imbalances by regulating NF-κB signaling pathway in type II collagen-induced rheumatoid arthritis model. Oligostilbenes were essential ingredients in ethyl acetate extract of C. stenophylla roots. Stilbenes and flavonoids should be responsible for its anti-rheumatoid arthritis activities.
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http://dx.doi.org/10.1016/j.jep.2021.114134DOI Listing
April 2021

TRIB3 Promotes the Malignant Progression of Bladder Cancer: An Integrated Analysis of Bioinformatics and Experiments.

Front Genet 2021 26;12:649208. Epub 2021 Mar 26.

Department of Physiology, Shenyang Medical College, Shenyang, China.

Background: Bladder cancer is a common malignant tumor characterized by high mortality and high management costs; however, it lacks useful molecular prognostic markers. Tribbles pseudokinase 3 (TRIB3) is a pseudokinase that participates in cell tumor progression and metabolism and whose function in bladder cancer is not precisely known.

Main Methods: We downloaded transcriptome data and clinical data of bladder cancer from associated databases and extracted the expression matrix of TRIB3 for multiple bioinformatics analysis. RT-PCR detected the expression of TRIB3 in bladder cancer cells. After knockdown of TRIB3 with siRNA, we investigated TRIB3 function using CCK8, Cell Cycle and Transwell assays.

Key Findings: Kaplan-Meier analysis of TRIB3 in the four cohorts showed that high expression of TRIB3 correlated with poor outcome. Expression of TRIB3 positively correlated with stage and grade and down-regulation of TRIB3 expression significantly inhibited proliferation, migration and cell cycle of bladder cancer cells.

Significance: TRIB3 is a potential prognostic marker and therapeutic target. It can be used to individualize the treatment of bladder cancer.
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http://dx.doi.org/10.3389/fgene.2021.649208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033215PMC
March 2021

Analysis of the operative factors related to anal exhaust time after laparoscopic surgery for benign gynecological diseases.

J Gynecol Obstet Hum Reprod 2021 Apr 8;50(8):102142. Epub 2021 Apr 8.

Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China; Department of Gynecology, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou 225001, China. Electronic address:

Purpose: The study seeks to determine surgical factors related to anal exhaust in patients treated with laparoscopic surgery for benign gynecological diseases and to explore measures that effectively promote the rapid recovery of intestinal function in these patients.

Methods: From June 2017 to August 2018, 155 patients with benign gynecological diseases who underwent laparoscopic surgery in our hospital were selected as study subjects. Patients were divided into two groups based on anal exhaust time: the ≤ 24-hour group and > 24-hour group. Factors related to the operation were statistically analyzed for all patients. Chi-squared tests and logistic regression were used for univariate and multivariable analyses.

Results: Of 155 gynecological patients, 57 (36.8%) underwent laparoscopic ovarian cyst stripping, 48 (30.9%) underwent laparoscopic salpingectomy with/without oophorectomy, and 50 (32.3%) underwent laparoscopic myomectomy. Among all patients, 62 (40.0%) and 93 (60.0%) had anal exhaust within and after 24 h, respectively. Univariate analysis results revealed differences in the operation method (P = 0.040), intraoperative blood loss (P = 0.037), operation duration (P = 0.007), whether an abdominal drainage tube was placed (P = 0.012) and whether warm saline was used (37 °C) for abdominal washing (P = 0.013) between groups. Logistic regression analysis showed that the duration of the operation (P = 0.027) and whether warm saline was used for abdominal washing (P = 0.040) were the main factors affecting anal exhaust time.

Conclusion: During laparoscopy for patients with benign gynecological diseases, abdominal washing with warm water is an important factor that promotes early postoperative anal exhaust and is worthy of use in clinical practice.
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http://dx.doi.org/10.1016/j.jogoh.2021.102142DOI Listing
April 2021

Interleukin-17A mediates tobacco smoke-induced lung cancer epithelial-mesenchymal transition through transcriptional regulation of ΔNp63α on miR-19.

Cell Biol Toxicol 2021 Apr 3. Epub 2021 Apr 3.

Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.

Interleukin-17A (IL-17A) is an essential inflammatory cytokine in the progress of carcinogenesis. Tobacco smoke (TS) is a major risk factor of lung cancer that influences epithelial-mesenchymal transition (EMT) process. However, the potential mechanism by which IL-17A mediates the progression of lung cancer in TS-induced EMT remains elusive. In the present study, it was revealed that the IL-17A level was elevated in lung cancer tissues, especially in tumor tissues of cases with experience of smoking, and a higher IL-17A level was correlated with induction of EMT in those specimens. Moreover, the expression of ΔNp63α was increased in IL-17A-stimulated lung cancer cells. ΔNp63α functioned as a key oncogene that bound to the miR-17-92 cluster promoter and transcriptionally increased the expression of miR-19 in lung cancer cells. Overexpression of miR-19 promoted EMT in lung cancer with downregulation of E-cadherin and upregulation of N-cadherin, while its inhibition suppressed EMT. Finally, the upregulated levels of IL-17A, ΔNp63α, and miR-19 along with the alteration of EMT-associated biomarkers were found in lung tissues of TS-exposed mice. Taken together, the abovementioned results suggest that IL-17A increases ΔNp63α expression, transcriptionally elevates miR-19 expression, and promotes TS-induced EMT in lung cancer. These findings may provide a new insight for the identification of therapeutic targets for lung cancer.
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http://dx.doi.org/10.1007/s10565-021-09594-0DOI Listing
April 2021

Congenital myasthenic syndrome in China: genetic and myopathological characterization.

Ann Clin Transl Neurol 2021 04 23;8(4):898-907. Epub 2021 Mar 23.

Department of Neurology, Peking University First Hospital, Beijing, China.

Objective: We aimed to summarize the clinical, genetic, and myopathological features of a cohort of Chinese patients with congenital myasthenic syndrome, and follow up on therapeutic outcomes.

Methods: The clinical spectrum, mutational frequency of genes, and pathological diagnostic clues of various subtypes of patients with congenital myasthenic syndrome were summarized. Therapeutic effects were followed up.

Results: Thirty-five patients from 29 families were recruited. Ten genes were identified: GFPT1 (27.6%), AGRN (17.2%), CHRNE (17.2%), COLQ (13.8%), GMPPB (6.9%), CHAT, CHRNA1, DOK7, COG7, and SLC25A1 (3.4% each, respectively). Sole limb-girdle weakness was found in patients with AGRN (1/8) and GFPT1 (7/8) mutations, whereas distal weakness was all observed in patients with AGRN (6/8) mutations. Tubular aggregates were only found in patients with GFPT1 mutations (5/6). The patients with GMPPB mutations (2/2) had decreased alpha-dystroglycan. Acetylcholinesterase inhibitor therapy resulted in no response or worsened symptoms in patients with COLQ mutations, a diverse response in patients with AGRN mutations, and a good response in patients with other subtypes. Albuterol therapy was effective or harmless in most subtypes. Therapy effects became attenuated with long-term use in patients with COLQ or AGRN mutations.

Interpretation: The genetic distribution of congenital myasthenic syndrome in China is distinct from that of other ethnic origins. The appearance of distal weakness, selective limb-girdle myasthenic syndrome, tubular aggregates, and decreased alpha-dystroglycan were indicative of the specific subtypes. Based on the follow-up findings, we suggest cautious evaluation of the long-term efficacy of therapeutic agents in congenital myasthenic syndrome.
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http://dx.doi.org/10.1002/acn3.51346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045908PMC
April 2021

Risk Factors for Long-Term Death After Medullary Infarction: A Multicenter Follow-Up Study.

Front Neurol 2021 4;12:615230. Epub 2021 Mar 4.

Department of Neurolgoy, People's Hospital of Zhengzhou University, Zhengzhou, China.

We investigated the risk factors for death in patients with medullary infarction (MI) during a long-term follow-up. We retrospectively examined 179 consecutive patients (130 men and 49 women) who had clinical and MRI findings consistent with MI between February 2012 and January 2017 at three university hospitals. Long-term outcomes were assessed by telephonic interview. The clinical and radiological features and risk factors for poor outcomes (modified Rankin scale score ≥ 3, all-cause death) were analyzed. Mean age of patients was 58.3 ± 12.8 years (range, 25-87); mean follow-up period after stroke onset was 42.7 ± 13.2 months (range, 24-78). Basilar artery (BA) stenosis >50% was more closely related to medial medullary infarction (MMI) than other types. There was greater frequency of ipsilateral vertebral artery hypoplasia (VAH) or V4AH and V4 occlusion in lateral MI than in other types. On rostro-caudal classification, middle (M)+dorsal (D) was most frequent, followed by the ventral (V)+M+D types. 21.2% patients showed poor long-term prognosis. Age ≥ 65 years, recurrent stroke, dysphagia, >50% BA stenosis, and ventral MI were risk factors for poor long-term prognosis. All-cause mortality rate was 10.6%; age ≥ 65 years, recurrent stroke, and dysphagia were risk factors for death in the long-term. Ventral MI and MMI+cerebellar infarction, as well as stroke mechanism of artery-to-artery embolism, were potential risk factors for death in the long-term. Pneumonia and recurrent stroke were major causes of death. Long-term poor outcomes of MI and all-cause mortality were not infrequent. Older age, recurrent stroke, and dysphagia were common risk factors for poor prognosis and death.
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http://dx.doi.org/10.3389/fneur.2021.615230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969705PMC
March 2021

Sirtuin 6 regulates the proliferation and survival of clear cell renal cell carcinoma cells via B-cell lymphoma 2.

Oncol Lett 2021 Apr 17;21(4):293. Epub 2021 Feb 17.

Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

Sirtuin 6 () is a member of the third family of longevity proteins (SIRTs) that is involved in the development of different types of cancer. However, the potential role of in clear cell renal cell carcinoma (ccRCC) and its molecular mechanism have not yet been fully elucidated. Therefore, the present study aimed to investigate the association between SIRT6 and ccRCC, and to further examine the underlying mechanism of its effect on ccRCC proliferation, using bioinformatics analysis, and and experiments. The results of the present study demonstrated that was upregulated in ccRCC tissues. In addition, bioinformatics analysis revealed that high expression was closely associated with poor prognosis of patients with ccRCC. experiments demonstrated that silencing expression in ccRCC-derived 769-P and 786-O cells significantly inhibited their proliferation, migration and invasion. Consistent with these results, assays demonstrated that knockdown markedly attenuated tumor growth arising from 769-P cells. Furthermore, depletion of enhanced the sensitivity of ccRCC cells to cisplatin. Notably, silencing expression decreased B-cell lymphoma 2 (Bcl-2) expression and increased Bax expression, respectively. Taken together, these results suggest that acts as a proto-oncogene in ccRCC through the augmentation of the Bcl-2-dependent pro-survival pathway, and may be used as a therapeutic target for patients with ccRCC.
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http://dx.doi.org/10.3892/ol.2021.12554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905630PMC
April 2021

Jasmonic acid-responsive RRTF1 transcription factor controls DTX18 gene expression in hydroxycinnamic acid amide secretion.

Plant Physiol 2021 Mar;185(2):369-384

Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Jasmonates (JAs) are plant hormones that regulate the biosynthesis of many secondary metabolites, such as hydroxycinnamic acid amides (HCAAs), through jasmonic acid (JA)-responsive transcription factors (TFs). HCAAs are renowned for their role in plant defense against pathogens. The multidrug and toxic compound extrusion transporter DETOXIFICATION18 (DTX18) has been shown to mediate the extracellular accumulation of HCAAs p-coumaroylagmatine (CouAgm) at the plant surface for defense response. However, little is known about the regulatory mechanism of DTX18 gene expression by TFs. Yeast one-hybrid screening using the DTX18 promoter as bait isolated the key positive regulator redox-responsive TF 1 (RRTF1), which is a member of the AP2/ethylene-response factor family of proteins. RRTF1 is a JA-responsive factor that is required for the transcription of the DTX18 gene, and it thus promotes CouAgm secretion at the plant surface. As a result, overexpression of RRTF1 caused increased resistance against the fungus Botrytis cinerea, whereas rrtf1 mutant plants were more susceptible. Using yeast two-hybrid screening, we identified the BTB/POZ-MATH (BPM) protein BPM1 as an interacting partner of RRTF1. The BPM family of proteins acts as substrate adaptors of CUL3-based E3 ubiquitin ligases, and we found that only BPM1 and BPM3 were able to interact with RRTF1. In addition, we demonstrated that RRTF1 was subjected to degradation through the 26S proteasome pathway and that JA stabilized RRTF1. Knockout of BPM1 and BPM3 in bpm1/3 double mutants enhanced RRTF1 accumulation and DTX18 gene expression, thus increasing resistance to the fungus B. cinerea. Our results provide a better understanding of the fine-tuned regulation of JA-induced TFs in HCAA accumulation.
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http://dx.doi.org/10.1093/plphys/kiaa043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133619PMC
March 2021

Molecular classification and clinical diagnosis of acute-on-chronic liver failure patients by serum metabolomics.

J Pharm Biomed Anal 2021 May 6;198:114004. Epub 2021 Mar 6.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China. Electronic address:

Prevalence of acute-on-chronic liver failure (ACLF) patients is growing worldwide, associating with multi-organ failure and high short-term mortality rates. ACLF can be of varying entity manifestation, whereas it remains poorly defined. Traditional Chinese medicine (TCM) stratifies ACLF into two types, damp hot (DH) and cold damp (CD), by seasoned TCM practitioners, for specific treatment with different TCMs. The biggest challenge for the outcome of TCM therapy is the accuracy of diagnosis. However, it is difficult to guarantee it due to lack of the molecule classification of ACLF. Herein, we recruited 58 subjects including 34 ACLF patients (18 DH and 16 CD) and 24 healthy controls, and analyzed serum metabolic profiles using untargeted ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomics approach. A total of 10 serum metabolites were found as potential biomarkers for diagnosis of ACLF. Among them, taurochenodesoxycholic acid (N3), glycyldeoxycholic acid (N5) and 12-HETE-GABA (N7), varied between two types of ACLF and can be merged as a combination marker to differentiate CD from DH patients with area under the receiver operating curve (AUC) of 0.928 (95 % CI 0.8-1). CD patients possessed comparatively higher bile acid metabolism and lower arachidonic acid metabolism compared with DH patients. The results provide not only serum molecules for early accurate diagnosis of ACLF patients, but also potential clinical biomarkers for classification of CD and DH types. The findings clarify that molecular markers will be objective criteria for diagnosis of clinical types in TCM practice.
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http://dx.doi.org/10.1016/j.jpba.2021.114004DOI Listing
May 2021