Publications by authors named "Xue Wang"

1,659 Publications

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MLN4924 inhibits hedgehog signaling pathway and activates autophagy to alleviate mouse laser-induced choroidal neovascularization lesion.

Biomed Pharmacother 2020 Oct 1;130:110654. Epub 2020 Sep 1.

Department of Ophthalmology, Lixiang Eye Hospital of Soochow University, Suzhou, Jiangsu, China. Electronic address:

Neovascular age-related macular degeneration (nAMD), featured as choroidal neovascularization (CNV), can cause blindness in the elderly population. MLN4924, a highly selective small-molecule inhibitor of NEDD8 (neuronal precursor cell-expressed developmentally down-regulated protein 8)-activating enzyme (NAE), inhibits the proliferation, angiogenesis and inflammation of multiple cancers via up-regulating hedgehog pathway-regulated autophagy. MLN4924 intraperitoneal injection mitigated the leakage, area and volume of mouse laser-induced CNV lesion. Additionally, compared to CNV 7 d group, MLN4924 treated mouse retina-retinal pigment epithelium (RPE)-choroid complex showed decreased expression of hedgehog pathway-associated molecules patched 1 (PTCH1), smoothened (SMO), GLI family zinc finger 1 (GLI1) and GLI family zinc finger 2 (GLI2) with increased expression of autophagy-associated molecules sequestosome 1 (p62) and LC microtubule-associated protein 1 light chain 3 (LC3). Meanwhile, human choroidal endothelial cells (HCECs) exposed to hypoxia condition also showed decreased expression of hedgehog pathway-associated molecules and increased expression of autophagy-associated molecules. Compared to hypoxia + MLN4924 group, SMO agonist SAG up-regulated hedgehog pathway and down-regulated autophagy, whereas autophagy inhibitor PIK-III inhibited autophagy with no effect on hedgehog pathway, indicating that MLN4924 facilitated autophagy of HCECs via hindering hedgehog pathway under hypoxia condition. Finally, MLN4924 inhibited proliferation, migration and tube formation of HCECs via boosting hedgehog pathway-regulated autophagy. In summary, MLN4924 relieved the formation of mouse laser-induced CNV lesion might via up-regulating hedgehog pathway-regulated autophagy. The results provide a potential interfering strategy for nAMD targeting the autophagy of choroidal endothelial cells.
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http://dx.doi.org/10.1016/j.biopha.2020.110654DOI Listing
October 2020

Incidence of post-traumatic stress disorder in survivors of traumatic fracture: a systematic review and meta-analysis.

Psychol Health Med 2021 Jul 27:1-15. Epub 2021 Jul 27.

Department of Epidemiology and Health Statistics, School of Public Health, Zunyi Medical University, Zunyi, China.

Post-traumatic stress disorder (PTSD) is prevalent in traumatic events. It is a great hazard of physical and mental health due to their severity and frequency. Traumatic fractures are one of the major causes of PTSD. The incidence of traumatic fractures has been high in recent years, which will directly or indirectly result in PTSD. Our target is to estimate the pooled incidence of PTSD in fracture patients after traumatic events and to explore possible influencing factors by a meta-analysis.The systematic searches in the electronic bibliographic databases of Web of Science, ScienceDirect, Ovid MEDLINE, PubMed, CNKI (China National Knowledge Infrastructure), Wangfang , and Veipu Databases. Not only were heterogeneity and 95% confidence interval (CI) used for comprehensive assessing each pooled, but also was the value. Subgroup analyses for some sample characteristics were calculated the pooled incidence of PTSD among patients suffered from fractures.In total, 2619 patients suffered from fracture, and were assessed PTSD in the 12 eligible studies. The heterogeneity was not low (I = 97.6%, < 0.001) in the 12 eligible studies. The pooled incidence of PTSD in fracture patients was 29% (95% CI, 20% to 39%) using random-effects model. Subgroup analyses revealed that the pooled incidence of PTSD among patients after traumatic fracture was statistically significant differences according to the study design, the study location, tools to assess the symptoms of PTSD, the mean age and injury mechanism (all < 0.001). Fracture sites, injury mechanism and pain were the main influencing factors of PTSD in fracture patients.Our results highlight the phenomenon that high incidence of PTSD in patients after fracture and they should be followed up regularly and be provided effective interventions. Future efforts to improve and control the main influencing factors of PTSD for this population still needed.
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http://dx.doi.org/10.1080/13548506.2021.1957953DOI Listing
July 2021

Application of 3-Alkyl-2-vinylindoles in Catalytic Asymmetric Dearomative (2+3) Cycloadditions.

J Org Chem 2021 Jul 27. Epub 2021 Jul 27.

School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, 221116, China.

The first application of 3-alkyl-2-vinylindoles in catalytic asymmetric dearomative cycloadditions was established by chiral phosphoric acid (CPA)-catalyzed (2+3) cycloaddition with azoalkenes, leading to the generation of chiral pyrroloindolines bearing two tetrasubstituted stereogenic centers in good yields (61-96%) and excellent stereoselectivities (all >95:5 dr, 86-99% ee). This reaction has realized the first enantioselective dearomative cycloaddition of 3-alkyl-2-vinylindoles, which brings a new reactivity to this class of vinylindoles and will enrich the chemistry of 3-alkyl-2-vinylindoles. In addition, this approach has provided a useful strategy for the construction of enantioenriched pyrroloindoline skeletons bearing two tetrasubstituted stereogenic centers. More importantly, the bioassay of these chiral pyrroloindolines has revealed that some compounds exhibit strong anti-cancer activity against Hela and MCF-7 cell lines, which will be helpful for discovering anti-cancer drug candidates.
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http://dx.doi.org/10.1021/acs.joc.1c01105DOI Listing
July 2021

Chronic stress promotes glioma cell proliferation via the PI3K/Akt signaling pathway.

Oncol Rep 2021 Sep 23;46(3). Epub 2021 Jul 23.

Institute of Military Cognitive and Brain Sciences, Academy of Military Medicine Sciences, Beijing 100850, P.R. China.

High malignancy and high mortality of glioma render it urgent to elucidate the underlying mechanisms of glioma carcinogenesis and explore novel targets for therapy. Epidemiologic and clinical studies have revealed that chronic stress promotes the progression of various solid tumors and is correlated with poor prognosis; however, findings reporting the involvement of chronic stress in glioma are rare. In the present study, a chronic restraint animal model and a chronic stress cell model were established to explore the effects of chronic stress on glioma and its molecular mechanisms. The results revealed that chronic stress promoted glioma growth , and the serum levels of the stress hormones glucocorticoid (GC) and noradrenaline (NE) were significantly increased. In addition, GC and NE were verified to accelerate the proliferation of glioma cells . Mechanistically, the phosphatidylinositol 3‑kinase (PI3K)/Akt signaling pathway was revealed to be activated under stress conditions, and inhibition of the expression of p‑Akt could restrain the stress hormone‑induced glioma cell proliferation. In addition, our data indicated that the GC receptor (GR) and β‑adrenergic receptors (ADRBs) were both required for the biological functions of GC and NE in glioma cells. In conclusion, these results indicated that chronic stress and the stress hormones GC and NE activated PI3K/Akt signaling through binding to GR and ADRBs, thereby promoting glioma cell growth. Our findings may provide potential therapeutic targets and pave the way for the development of new strategies to protect patients with glioma from the detrimental effects of stress on tumor progression.
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http://dx.doi.org/10.3892/or.2021.8153DOI Listing
September 2021

Apparent Treatment-Resistant Hypertension Assessed by Office and Ambulatory Blood Pressure in Chronic Kidney Disease-A Report from the Chronic Renal Insufficiency Cohort Study.

Kidney360 2020 Aug;1:810-818

Department of Medicine, University Hospitals Cleveland Medical Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Case Western Reserve University, Cleveland, Ohio.

Background: Apparent treatment-resistant hypertension is common in patients with CKD. Whether measurement of 24-hour ambulatory BP monitoring is valuable for risk-stratifying patients with resistant hypertension and CKD is unclear.

Methods: We analyzed data from the Chronic Renal Insufficiency Cohort study, a prospective study of participants (=1186) with CKD. Office BP was measured using standardized protocols; ambulatory BP was measured using Spacelabs monitors. Apparent treatment-resistant hypertension was defined on the basis of office BP, ambulatory BP monitoring, and use of more than three antihypertensive medications. Outcomes were composite cardiovascular disease, kidney outcomes, and mortality. Groups were compared using Cox regression analyses with a control group of participants without apparent treatment-resistant hypertension.

Results: Of 475 participants with apparent treatment-resistant hypertension on the basis of office BP, 91.6% had apparent treatment-resistant hypertension confirmed by ambulatory BP monitoring. Unadjusted event rates of composite cardiovascular disease, kidney outcomes, and mortality were higher in participants with ambulatory BP monitoring-defined apparent treatment-resistant hypertension compared with participants without apparent treatment-resistant hypertension. In adjusted analyses, the risks of composite cardiovascular disease (hazard ratio, 1.27; 95% confidence interval [95% CI], 0.59 to 2.7), kidney outcomes (hazard ratio, 1.68; 95% CI, 0.88 to 3.21), and mortality (hazard ratio, 1.27; 95% CI, 0.5 to 3.25) were not statistically significantly higher in participants with ambulatory BP monitoring-defined apparent treatment-resistant hypertension compared with participants without apparent treatment-resistant hypertension.

Conclusions: In our study population with CKD, most patients with apparent treatment-resistant hypertension defined on the basis of office BP have apparent treatment-resistant hypertension confirmed by ambulatory BP monitoring. Although ABPM-defined apparent treatment-resistant hypertension was not independently associated with clinical outcomes, it identified participants at high risk for adverse clinical outcomes.
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http://dx.doi.org/10.34067/KID.0002072020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298012PMC
August 2020

[Influences of severe obstructive sleep apnea on cognitive function].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 Jun;35(6):511-516

Department of Otorhinolaryngology Head and Neck Surgery,First Affiliated Hospital of Nanchang University,Nanchang,330006,China.

To explore the differences in cognitive function between patients with severe OSA and non-moderate OSA. The MoCA scale was used to evaluate the overall cognitive function and sub-items in 196 subjects who received polysomnography; and the SDMT and TMT-A scales were used to evaluate the performance in test of attention and information processing speed in 161 patients. The clinical information, physical examination data and related polysomnography data were collected. According to AHI, subjects were divided into two groups: severe OSA and non-to-moderate OSA. Before and after correction of confounding factors, the differences in cognitive scale evaluation indicators were compared between the two groups. We used linear regression analysis to clarify the independent influencing factors of cognitive functions, and to determine whether severe OSA is independently related to cognitive abilities. After correcting for multiple factors, the delayed recall score and total score of the MoCA scale and the correct number of SDMT in the severe OSA group were significantly lower than those in the non-to-moderate OSA group(<0.05). Linear regression analysis showed that severe OSA was independently negatively correlated with the delayed recall score, total score and SDMT correct number in the MoCA scale(<0.05). Compared with non-to-moderate OSA, subjects with severe OSA have significant decline in overall cognition, delayed recall, attention and processing speed. Severe OSA may be an independent influencing factor of overall cognition, delayed recall, attention and processing speed.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2021.06.006DOI Listing
June 2021

Rational construction of genome-reduced Burkholderiales chassis facilitates efficient heterologous production of natural products from proteobacteria.

Nat Commun 2021 07 23;12(1):4347. Epub 2021 Jul 23.

Helmholtz International Lab for Anti-Infectives, Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong, China.

Heterologous expression of biosynthetic gene clusters (BGCs) avails yield improvements and mining of natural products, but it is limited by lacking of more efficient Gram-negative chassis. The proteobacterium Schlegelella brevitalea DSM 7029 exhibits potential for heterologous BGC expression, but its cells undergo early autolysis, hindering further applications. Herein, we rationally construct DC and DT series genome-reduced S. brevitalea mutants by sequential deletions of endogenous BGCs and the nonessential genomic regions, respectively. The DC5 to DC7 mutants affect growth, while the DT series mutants show improved growth characteristics with alleviated cell autolysis. The yield improvements of six proteobacterial natural products and successful identification of chitinimides from Chitinimonas koreensis via heterologous expression in DT mutants demonstrate their superiority to wild-type DSM 7029 and two commonly used Gram-negative chassis Escherichia coli and Pseudomonas putida. Our study expands the panel of Gram-negative chassis and facilitates the discovery of natural products by heterologous expression.
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http://dx.doi.org/10.1038/s41467-021-24645-0DOI Listing
July 2021

Cooperative Motion in Water-Methanol Clusters Controls the Reaction Rates of Heterogeneous Photocatalytic Reactions.

J Am Chem Soc 2021 Jul 19;143(29):10940-10947. Epub 2021 Jul 19.

Physics Department & Shanghai Key Laboratory of Magnetic Resonance, School of Physics and Electronic Science, East China Normal University, North Zhongshan Road 3663, Shanghai 200062, People's Republic of China.

Detailed information about the influences of the cooperative motion of water and methanol molecules on practical solid-liquid heterogeneous photocatalysis reactions is critical for our understanding of photocatalytic reactions. The present work addresses this issue by applying operando nuclear magnetic resonance (NMR) spectroscopy, in conjunction with density functional theory (DFT) calculations and ab initio molecular dynamics (AIMD) simulations, to investigate the dynamic behaviors of heterogeneous photocatalytic systems with different molar ratios of water to methanol on rutile-TiO photocatalyst. The results demonstrate that methanol and water molecules are involved in the cooperative motions, and the cooperation often takes the form of methanol-water clusters that govern the number of methanol molecules reaching to the active sites of the photocatalyst per unit time, as confirmed by the diffusion coefficients of the methanol molecule calculated in the binary methanol-water solutions. Nuclear Overhauser effect spectroscopy experiments reveal that the clusters are formed by the hydrogen bonding between the -OH groups of CHOH and HO. The formation of such methanol-water clusters is likely from an energetic standpoint in low-concentration methanol, which eventually determines the yields of methanol reforming products.
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http://dx.doi.org/10.1021/jacs.1c02128DOI Listing
July 2021

Long-term running exercise alleviates cognitive dysfunction in APP/PSEN1 transgenic mice via enhancing brain lysosomal function.

Acta Pharmacol Sin 2021 Jul 16. Epub 2021 Jul 16.

Department of Pharmacology, Laboratory of Aging and Nervous Diseases (SZS0703), Jiangsu Key Laboratory of Neuropsychiatric Disease, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.

Amyloid-β peptide (Aβ) aggregation is the hallmark of Alzheimer's disease (AD). The imbalance between the production and clearance of Aβ results in the accumulation and aggregation of Aβ in the brain. Thus far, few drugs are available for AD treatment, but exercise has been recognized for its cognition-enhancing properties in AD patients. The underlying mechanisms remain unclear. Our recent study showed that long-term running exercise could activate the lysosomal function in the brains of mice. In this study, we investigated whether exercise could reduce Aβ accumulation by activating lysosomal function in APP/PSEN1 transgenic mice. Started at the age of 5 months, the mice were trained with a running wheel at the speed of 18 r/min, 40 min/d, 6 d/week for 5 months, and were killed at the end of the 10th month, then brain tissue was collected for biochemical analyses. The cognitive ability was assessed in the 9th month. We showed that long-term exercise significantly mitigated cognitive dysfunction in AD mice, accompanied by the enhanced lysosomal function and the clearance of Aβ in the brain. Exercise significantly promoted the nuclear translocation of transcription factor EB (TFEB), and increased the interaction between nuclear TFEB with AMPK-mediated acetyl-CoA synthetase 2, thus enhancing transcription of the genes associated with the biogenesis of lysosomes. Exercise also raised the levels of mature cathepsin D and cathepsin L, suggesting that more Aβ peptides could be degraded in the activated lysosomes. This study demonstrates that exercise may improve the cognitive dysfunction of AD by enhancing lysosomal function.
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http://dx.doi.org/10.1038/s41401-021-00720-6DOI Listing
July 2021

Differences in the individual curative effect of acupuncture for obese women with polycystic ovary syndrome based on metagenomic analysis: study protocol for a randomized controlled trial.

Trials 2021 Jul 15;22(1):454. Epub 2021 Jul 15.

School of Acupuncture-Moxibustion and Tuina/The Third Affiliated Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Background: Polycystic ovary syndrome is a common cause of infertility and shows a high incidence in women of reproductive age. Acupuncture is an appropriate adjunctive treatment for PCOS. However, the add-on effect of acupuncture as an adjunctive treatment for obese women with PCOS has not been studied, and previous studies indicate that there are individual differences in the curative effect of acupuncture, while deeper research on the mechanism of differences in the individual curative effect of acupuncture for obese women with PCOS is still lacking. This trial aims to assess the add-on treatment efficacy of acupuncture for obese women with PCOS and to explore the role of the gut microbiome on the differences in the individual curative effect of acupuncture based on metagenomic analysis.

Methods/design: This is an open-label, randomized, controlled trial. A total of 86 obese women with PCOS will be recruited. Subjects will be randomly assigned to a study group and a control group in a 1:1 ratio, with 43 subjects in each group (10 patients from each group who meet the study criteria will participate in the metagenomic analysis). An additional 10 subjects who meet the study criteria will be recruited to a healthy control group. The study group will receive acupuncture and clomiphene citrate treatment; the control group will only receive clomiphene citrate. Acupuncture treatment will be conducted three times a week from the fifth day of menstruation or withdrawal bleeding until the start of the next menstruation, for up to three menstrual cycles. The primary outcome will be LH/FSH. The secondary outcomes will comprise biometric features, hormone biomarkers, metabolic biomarkers, inflammatory biomarkers, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and metagenomic analysis. The outcomes will be measured at baseline and post-intervention. Data will be analyzed using SPSS 19.0, and the gut microbiome will be analyzed using metagenomic analysis.

Discussion: In this study, we are evaluating the add-on effects of acupuncture and exploring the mechanism of the differences in the individual curative effect of acupuncture based on the gut microbiome, which may provide evidence to explain the different outcomes of different trials on acupuncture for PCOS and hopefully to provide a new aspect to study the mechanism of acupuncture's treatment effect.

Trial Registration: Chinese Clinical Trial Registry ChiCTR2000029882 . Registered on 16 February 2020.
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http://dx.doi.org/10.1186/s13063-021-05426-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281710PMC
July 2021

Downregulating lncRNA NEAT1 induces proliferation and represses apoptosis of ovarian granulosa cells in polycystic ovary syndrome via microRNA-381/IGF1 axis.

J Biomed Sci 2021 Jul 15;28(1):53. Epub 2021 Jul 15.

Department of Gynecological Endocrinology and Reproduction Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 41 Damucang Hutong, Xicheng, Beijing, China.

Objective: Researchers have revealed the combined functions of long noncoding RNAs (lncRNAs) and microRNA (miRNAs) in polycystic ovary syndrome (PCOS). This study aimed to understand the role of nuclear-enriched abundant transcript 1 (NEAT1) and miR-381 involving insulin-like growth factor 1 (IGF1) in PCOS.

Methods: PCOS rat model was established by dehydroepiandrosterone induction. NEAT1, miR-381 and IGF1 expression in ovarian granulosa cells of PCOS patients and ovarian tissues of PCOS rats were tested. Bioinformatics website and dual luciferase reporter gene assay were utilized to verify the relationship between NEAT1 and miR-381 and that between miR-381 and IGF1. Levels of sex hormone, pathological changes and ovarian granulosa cell apoptosis in ovarian tissues of PCOS rats were detected. Ovarian granulosa cell proliferation and apoptosis were analyzed in vitro.

Results: NEAT1 and IGF1 expression increased while miR-381 expression decreased in the ovarian granulosa cells of patients with PCOS and the ovarian tissues of PCOS rats. In in vivo experiments, interference with NEAT1 improved the levels of sex hormones, alleviated pathological changes and suppressed ovarian granulosa cell apoptosis in the ovarian tissues of PCOS rats. In in vitro cell experiments, interference with NEAT1 suppressed apoptosis and enhanced cell proliferation of ovarian granulosa cells. NEAT1 interference-mediated effect would be reversed by up-regulating miR-381. NEAT1 acted as a ceRNA to adsorb miR-381 to target IGF1. Overexpression of IGF1 reversed the inhibitory effect of miR-381 on ovarian granulosa cell apoptosis.

Conclusion: Interference with NEAT1 increases miR-381 and reduces IGF1 levels, effectively improving the levels of sex hormones and reducing the pathological damage of ovarian tissue in rats with PCOS.
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http://dx.doi.org/10.1186/s12929-021-00749-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281489PMC
July 2021

6-lncRNA Assessment Model for Monitoring and Prognosis of HER2-Positive Breast Cancer: Based on Transcriptome Data.

Pathol Oncol Res 2021 13;27:609083. Epub 2021 Apr 13.

College of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.

In view of the high malignancy and poor prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, we analyzed the RNA expression profiles of HER2-positive breast cancer samples to identify the new prognostic biomarkers. The linear fitting method was used to identify the differentially expressed RNAs from the HER2-positive breast cancer RNA expression profiles in the Cancer Genome Atlas (TCGA). Then, a series of methods including univariate Cox, Kaplan-Meier, and random forests, were used to identify the core long non-coding RNAs (lncRNAs) with stable prognostic value for HER2-positive breast cancer. A clinical feature analysis was performed, and a competing endogenous RNA network was constructed to explore the role of these core lncRNAs in HER2-positive breast cancer. In addition, a functional analysis of differentially expressed messenger RNAs in HER-2 positive breast cancer also provided us with some enlightening insights. The high expression of four core lncRNAs (AC010595.1, AC046168.1, AC069277.1, and AP000904.1) was associated with worse overall survival, while the low expression of LINC00528 and MIR762HG was associated with worse overall survival. The 6-lncRNA model has an especially good predictive power for overall survival ( < 0.0001) and 3-year survival (the area under the curve = 0.980) in HER2-positive breast cancer patients. This study provides a new efficient prognostic model and biomarkers of HER2-positive breast cancer. Meanwhile, it also provides a new perspective for elucidating the molecular mechanisms underlying HER2-positive breast cancer.
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http://dx.doi.org/10.3389/pore.2021.609083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262145PMC
April 2021

miR-100-5p in human umbilical cord mesenchymal stem cell-derived exosomes mediates eosinophilic inflammation to alleviate atherosclerosis via the FZD5/Wnt/β-catenin pathway.

Acta Biochim Biophys Sin (Shanghai) 2021 Jul 13. Epub 2021 Jul 13.

Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.

Exosomes derived from human umbilical cord mesenchymal stem cells (hUMSC-Ex) play important roles in immune and inflammation diseases. However, the role of hUMSC-Ex in atherosclerosis has not been elucidated. In this study, the isolated exosomes were identified by transmission electron microscopy and nanoparticle tracking analysis. Exosome marker protein levels were increased in the hUMSC-Ex compared with those in hUMSC suspension, indicating that exosomes were successfully isolated from hUMSCs. Furthermore, eosinophils were treated with oxidized low-density lipoprotein (ox-LDL) to construct inflammation model and then incubated with hUMSC-Ex derived from hUMSCs which were transfected with miR-100-5p mimic or miR-100-5p inhibitor. We found that hUMSC-Ex increased miR-100-5p expression, inhibited cell migration, promoted cell apoptosis, and reduced inflammatory cytokine levels in ox-LDL-treated eosinophils, and miR-100-5p overexpression in hUMSCs enhanced these effects, while miR-100-5p inhibition reversed these effects. Moreover, frizzled 5 (FZD5) was a target gene of miR-100-5p. FZD5 overexpression reversed the inhibitory effects of hUMSC-Ex-miR-100-5p on cell progression and inflammation in eosinophils. Additionally, hUMSC-Ex-miR-100-5p decreased the expression of cyclin D1 and β-catenin proteins. Wnt/β-catenin pathway activator BML-284 effectively reversed the effects of hUMSC-Ex-miR-100-5p on cell progression and inflammation in eosinophils. ApoE-/- mice were fed with high-fat diet to construct an atherosclerosis mice model, and hUMSC-Ex was injected into mice. HUMSC-Ex reduced atherosclerotic plaque area and inflammation response in atherosclerosis mice. This study demonstrates that hUMSC-Ex-miR-100-5p inhibits cell progression and inflammatory response in eosinophils via the FZD5/Wnt/β-catenin pathway, thereby alleviating atherosclerosis progression.
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http://dx.doi.org/10.1093/abbs/gmab093DOI Listing
July 2021

Developmental toxicity caused by sanguinarine in zebrafish embryos via regulating oxidative stress, apoptosis and wnt pathways.

Toxicol Lett 2021 Jul 9;350:71-80. Epub 2021 Jul 9.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Shandong Provincial Engineering Laboratory for Biological Testing Technology, 28789 Jingshidong Road, Licheng District, Jinan, 250103, Shandong Province, PR China. Electronic address:

Sanguinarine, derived from the root of Sanguinaria canadensis, have multiple biological activities, such as antimicrobial, insecticidal, antitumor, anti-inflammatory and anti-angiogenesis effect, but little is known about its toxicity on normal embryonic development. Here, we study the developmental toxicity using zebrafish model. Notably, sanguinarine caused a significant increase of the malformation rate and decrease of hatching rates and body length of zebrafish embryos. Sanguinarine also impaired the normal development of heart, liver and nerve system of zebrafish embryos. Further, the ROS level and MDA concentrations were remarkably increased, while the activity of T-SOD was decreased. In addition, obvious increase of apoptosis were observed by AO staining or TUNEL assay. Further studies showed that the oxidative stress-, apoptosis-related genes were changed, while genes of nrf2 and wnt pathways were inhibited by sangunarine. To sum up, our study will be helpful to understand the adverse effect of sanguinarine on embryonic development and the underlying molecular mechanism.
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http://dx.doi.org/10.1016/j.toxlet.2021.07.001DOI Listing
July 2021

Sarsasapogenin restores podocyte autophagy in diabetic nephropathy by targeting GSK3β signaling pathway.

Biochem Pharmacol 2021 Jul 9:114675. Epub 2021 Jul 9.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China. Electronic address:

Podocyte injury following abnormal podocyte autophagy plays an indispensable role in diabetic nephropathy (DN), therefore, restoration of podocyte autophagy is considered as a feasible strategy for the treatment of DN. Here, we investigated the preventive effects of sarsasapogenin (Sar), the main active ingredient in Anemarrhena asphodeloides Bunge, on the podocyte injury in diabetic rats, and tried to illustrate the mechanisms underlying the effects in high glucose (HG, 40 mM)-treated podocytes (MPs). Diabetes model was established in rats with single streptozocin (60 mg· kg) intraperitoneal administration. The rats were then treated with Sar (20, 60 mg· kg· d, i.g.) or a positive control drug insulin (INS) (40 U· kg· d, i.h.) for 10 weeks. Our results showed that both Sar and insulin precluded the decreases of autophagy-related proteins (ATG5, Beclin1 and LC3B) and podocyte marker proteins (podocin, nephrin and synaptopodin) in the diabetic kidney. Furthermore, network pharmacology was utilized to assess GSK3β as the potential target involved in the action of Sar on DN and were substantiated by significant changes of GSK3β signaling in the diabetic kidney. The underlying protection mechanisms of Sar were explored in HG-treated MPs. Sar (20, 40 μM) or insulin (50 mU/L) significantly increased the expression of autophagy- related proteins and podocyte marker proteins in HG-treated MPs. Furthermore, Sar or insulin treatment efficiently regulatedphosphorylation at activation and inhibition sites of GSK3β. To sum up, this study certifies that Sar meliorates experimental DN through targeting GSK3β signaling pathway and restoring podocyte autophagy.
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http://dx.doi.org/10.1016/j.bcp.2021.114675DOI Listing
July 2021

Lignin Nanoparticles: Promising Sustainable Building Blocks of Photoluminescent and Haze Films for Improving Efficiency of Solar Cells.

ACS Appl Mater Interfaces 2021 Jul 12;13(28):33536-33545. Epub 2021 Jul 12.

Engineering Research Center of Advanced Wooden Materials, Ministry of Education, Northeast Forestry University, Hexing Road 26, Harbin 150040, P. R. China.

Films with the capacity for photoluminescence and haze, which can convert UV to visible light and enhance light management, are of great importance for optoelectronic devices. Here, taking advantage of the inherent fluorescence and self-assembly properties of lignin, we have developed a sustainable lignin-derived multifunctional dopant (L-MS-NPs) for fabricating optical films with haze, fluorescence, and room-temperature phosphorescence (RTP) together with poly(vinyl alcohol) (PVA). The optical films are used to improve the light-harvesting efficiency of solar cells. Specifically, attributed to the robust morphology in the film matrix, L-MS-NPs cause a rough morphology in the surface of an L-MS-NPs/PVA composite film, which eventually triggers the great optical haze. Additionally, L-MS-NPs inherit fluorescence properties from lignin and show fluorescence emission when embed in the film matrix. Moreover, the PVA film matrix can stabilize the excited triplet state, which finally induces RTP of L-MS-NPs. The combined haze, fluorescence, and RTP properties of the L-MS-NPs/PVA composite film enhances the power conversion efficiency (PCE) of dye-sensitized solar cells from ∼3.9 to ∼4.1%.
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http://dx.doi.org/10.1021/acsami.1c08209DOI Listing
July 2021

Inverse Correlation Between Distress and Performance in the Medical Rescuers Against COVID-19 in Wuhan.

Front Psychiatry 2021 24;12:563533. Epub 2021 Jun 24.

Department of Stress Medicine, Institute of Basic Medical Sciences, Academy of Military Medical Sciences, Beijing, China.

During the COVID-19 pandemic, the Chinese government had transferred many medical rescuers to Wuhan, which provided effective support in disease control. The high-intensity working and mental stress during rescue could induce distress and negatively impact the performance of rescuer afterward. To identify the characteristics of stress load and its possible effects on performance, the study surveyed 90 medical rescuers in Wuhan using a mobile phone-based self-rated questionnaire. The results showed an existence of universal but mostly mild distress in rescuers. About 95.6% of the participants reported that they had at least one symptom of distress, whereas, the median scores were <30 (100 as max). Compared with civilian rescuers, a higher proportion of working with immediate virus contact was found in military medical rescuers ( = 0.008); however, no statistical differences of stress load were found between civilians and militaries. The rescuers with positive cognition or good psychological preparation were found having lower stress loads than other rescuers. An inverse correlation between the stress load and performance (R = -0.24, = 0.023) and a positive correlation between social support and working performance (R = 0.349, = 0.001) were found in our survey, suggesting the possible negative effects of stress and the beneficial effects of social support on performance. Our study indicated that more attention should be paid to the distress of medical rescuers against COVID-19. Positive cognitions, good psychological preparations, and sufficient social support would be necessary to reduce the distress and improve the performance in COVID-19 rescue.
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http://dx.doi.org/10.3389/fpsyt.2021.563533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264201PMC
June 2021

Effect of Ulinastatin on Early Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Surgery: A Systemic Review and Meta-Analysis.

Front Neurosci 2021 21;15:618589. Epub 2021 Jun 21.

Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Postoperative cognitive dysfunction (POCD) is associated with neuroinflammation by triggering the systemic inflammatory responses. Related studies have demonstrated that ulinastatin, which is a urinary trypsin inhibitor, inhibited the release of inflammatory mediators and improved postoperative cognitive function in elderly patients undergoing major surgery. However, there are controversial results put forwarded by some studies. This systemic review aimed to evaluate the effect of ulinastatin on POCD in elderly patients undergoing surgery. We searched PubMed, Embase, Cochrane Library, Web of Science, and Ovid to find relevant randomized controlled trials (RCTs) of ulinastatin on POCD in elderly patients undergoing surgery. The primary outcomes included the incidence of POCD and the Mini-Mental State Examination (MMSE) scores. The secondary outcome was the levels of inflammatory cytokines such as tumor necrosis factor (TNF)-α, S100β, C-reactive protein (CRP), interleukin (IL)-6, and IL-10. RevMan 5.3 was used to conduct the meta-analysis. Ten RCTs were included finally. Compared with controls, ulinastatin significantly reduced the incidence of POCD [risk ratio (RR) = 0.29, 95% CI 0.21-0.41, test of RR = 1: = 7.05, < 0.00001]. In addition, patients in the ulinastatin group have lower levels of TNF-α, S100β, CRP, and IL-6 and higher level of IL-10 in serum following surgery. These findings suggested that ulinastatin can be used as an anti-inflammatory drug for POCD prevention in elderly patients undergoing surgery. CRD42019137449.
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http://dx.doi.org/10.3389/fnins.2021.618589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265373PMC
June 2021

Regulating the Self-Discharge of Flexible All-Solid-State Supercapacitors by a Heterogeneous Polymer Electrolyte.

Small 2021 Jul 9:e2102054. Epub 2021 Jul 9.

Shanghai Key Lab of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, China.

Supercapacitors with high power density and an ultralong cyclic lifetime have been intensively investigated. However, the crucial challenge of their rapid self-discharge process is often neglected in most cases. A heterogeneous interface formed between two layers of polymer electrolytes is designed, in which a polyanion and a polycation are added into a common matrix of polymer electrolyte, respectively. By using the heterogeneous polymer electrolyte (HPE) as the separator simultaneously, the resultant supercapacitors exhibit comparable electrochemical performance to that of devices based on traditional polymer electrolytes. The HPE-based supercapacitors using both electric double-layer capacitive and pseudocapacitive electrodes show at least one time longer self-discharge time than that of devices based on homogenous polymer electrolyte, especially for the electrode in an electrolyte containing polyanion served as a positive pole during the charging process. Because of the same polymer matrix used, the heterojunction structure of the HPE exhibits excellent stability without obvious phase separation during thousands of charge/discharge and repeated bending cycles. This novel strategy by interface engineering of electrolyte to suppress the self-discharge behavior of supercapacitors is very meaningful to promote their practical applications.
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http://dx.doi.org/10.1002/smll.202102054DOI Listing
July 2021

The relationship between maternal perfluoroalkylated substances exposure and low birth weight of offspring: a systematic review and meta-analysis.

Environ Sci Pollut Res Int 2021 Jul 9. Epub 2021 Jul 9.

Department of Occupational and Environmental Health, School of Public Health, Hebei Key Laboratory of Environment and Human Health, Hebei Medical University, Zhongshan East Road 361, Shijiazhuang, 050017, Hebei, People's Republic of China.

Some studies have shown that maternal perfluoroalkylated substances (PFAS) exposure may be associated with low birth weight (LBW) of offspring. We conducted a meta-analysis to assess the association between maternal PFASs exposure and LBW in offspring. The researchers searched PubMed, Science Direct, Scopus, Google Scholar, Web of Science, and Embase to find all the articles before October 2020. The Newcastle-Ottawa Scale was used to evaluate the quality of the studies. Finally, six articles were included for meta-analysis. Our meta-analysis showed no significant correlation between maternal perfluorooctanoic acid (PFOA) exposure and LBW of offspring: odds ratio (OR) = 0.90, 95% confidence interval (95% CI) = 0.80-1.01, with low heterogeneity (I = 18.4%, P = 0.289); there was a significant positive correlation between maternal perfluorooctane sulfonate (PFOS) exposure and LBW of offspring (OR = 1.32, 95% CI = 1.09-1.55) with no heterogeneity (I = 0.00%, P = 0.570). The grouping analysis of PFOS showed was a significant positive correlation between maternal PFOS exposure and LBW of offspring in American (OR = 1.44, 95% CI = 1.15-1.72). This study provided a systematic review and meta-analysis evidence for the relationship between maternal PFASs exposure and LBW of offspring through a small number of studies. Researchers should conduct further studies between different regions.
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http://dx.doi.org/10.1007/s11356-021-15061-4DOI Listing
July 2021

The association between maternal perfluoroalkyl substances exposure and early attention deficit hyperactivity disorder in children: a systematic review and meta-analysis.

Environ Sci Pollut Res Int 2021 Jul 9. Epub 2021 Jul 9.

Department of Occupational and Environmental Health, School of Public Health, Hebei Medical University, Hebei Key Laboratory of Environment and Human Health, Zhongshan East Road 361, Shijiazhuang, 050017, Hebei, People's Republic of China.

Some studies have shown that maternal exposure to perfluoroalkyl substances (PFASs) may be associated with early attention deficit hyperactivity disorder (ADHD) in children. The purpose of this systematic review and meta-analysis is to verify this association by reviewing existing studies and to provide a strong basis for preventing ADHD. The researchers searched electronic databases such as PubMed, Science Direct, Scopus, Google Scholar, Web of Science, and Embase for all studies published before October 2020. Finally, we included nine articles for analysis. Our meta-analysis showed that maternal exposure to PFASs was not significantly associated with the prevalence rate of early childhood ADHD (perfluorooctanoic acid (PFOA), odds ratio (OR) = 1.00, 95% confidence interval (95% CI) = 0.75-1.25; perfluorooctane sulfonate (PFOS), OR = 1.01, 95% CI = 0.88-1.14; perfluorohexane sulfonate (PFHxS), OR = 1.08, 95% CI = 0.80-1.09; perfluorononanoic acid (PFNA), OR = 1.13, 95% CI = 0.99-1.28; perfluorodecanoic acid (PFDA), OR = 1.23, 95% CI = 0.15-2.32). Due to significant heterogeneity, we subsequently performed subgroup analysis and sensitivity analysis. Through subgroup analysis, we found that PFOS concentration of children's blood and the prevalence rate of early childhood ADHD were statistically positively correlated, and there was also a positive correlation between PFOS exposure and the prevalence rate of early childhood ADHD in the America. Moreover, there was also a statistically positive correlation between PFNA concentration in maternal blood and the prevalence rate of early childhood ADHD. Sensitivity analysis showed that the final results did not change much, the sensitivity was low, and the results were relatively stable. In conclusion, a causal relationship between maternal PFASs exposure and ADHD in children was unlikely. Among them, PFOS, PFNA, and ADHD might have positive associations worthy of further investigation.
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http://dx.doi.org/10.1007/s11356-021-15136-2DOI Listing
July 2021

Efficacy and Mechanism of Buxue Yimu Pills () on Gynecological Anemia: A Combination of Clinical and Network Pharmacology Study.

Chin J Integr Med 2021 Jul 9. Epub 2021 Jul 9.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.

Objective: To compare the clinical efficacy and safety of oral administration of Buxue Yimu Pills (BYP, ), ferrous sulfate (FS), and the combination of BYP and FS on gynecological anemia, and investigate the mechanisms using network pharmacology.

Methods: A randomized, controlled, multi-center clinical trial was conducted. Totally 150 patients with hemoglobin of 70-110 g/L due to gynecological conditions were recruited and randomized (using the block randomization method) into Buxue Yimu Pills group (24 g/d), oral iron group (FS Tablets, 0.9 g/d), and combined treatment group (BYP, 24 g/d plus FS Tablets, 0.9 g/d), 50 patients in each group. At the enrollment and 4-week treatment, complete blood count, serum iron indexes were evaluated. Adverse events, liver and renal functions, as well as blood coagulation were observed. Network pharmacology was conducted to identify the active ingredients and explore the potential mechanisms of BYP.

Results: Ten (20%) and 7 (14%) participants discontinued the therapy due to gastrointestinal symptoms in oral iron and combination treatment groups. All 3 groups showed elevated hemoglobin. The patients in the iron group exhibited typically elevated in serum iron and ferritin and decreased in total iron-binding capacity. No change in iron indexes was observed in BYP group. The patients in the combination treatment group neither showed significant changes in serum ferritin nor total iron-binding capacity. No significant adverse reactions were observed in the BYP group. The network pharmacology identified 27 bioactive compounds and 145 targets of BYP on gynecological anemia. Biological processes and pathways including regulation of inflammation, hormone, angiogenesis and hemostasis, response to decreased oxygen levels, effects on myeloma cell, and response to metal ions were identified.

Conclusion: BYP contributes to the practical improvement on gynecological anemia potentially through multi-target mechanisms and optimized iron re-distribution. (Trial registration: No. NCT03232554).
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http://dx.doi.org/10.1007/s11655-021-3296-7DOI Listing
July 2021

Effect of the ratio of vessel-specific volume to fractional myocardial mass on fractional flow reserve.

Exp Biol Med (Maywood) 2021 Jul 8:15353702211027119. Epub 2021 Jul 8.

Department of Biomedical Engineering, Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China.

This study aimed to examine whether the ratio of vessel-specific coronary arterial lumen volume to the fraction of myocardial mass (V/M) affects myocardial ischemia. We proposed a calculation method for V/M, and compared the ratio of total epicardial coronary arterial lumen volume to left ventricular myocardial mass (V/M) with V/M in predicting myocardial ischemia. V/M and V/M were computed using data from 205 patients with 241 stenosis vessel who underwent coronary computed tomography angiography (CTA), quantitative coronary angiography, and fractional flow reserve. The vessel-specific coronary arterial lumen volume (V) was obtained from CTA by segmenting the coronary arterial lumen volume, while the vessel-specific fraction of myocardial mass (M) was obtained by allometric scaling. The V/M was then calculated. The cut-off values of V/M (23.55 mm/g) and V/M (12.98 mm/g) were used to define equal groups of ischemic and non-ischemic patients, respectively. Using these cut-off values, the accuracy, specificity, sensitivity, positive predictive value, and negative predictive value of V/M were 60%, 76%, 45%, 57%, and 66%, and of V/M were 87%, 92%, 77%, 89%, and 83%, respectively. Patients have different V/M values in different stenotic coronary arteries. Clinically, V/M is a quantitative indicator of the risk of myocardial ischemia.
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http://dx.doi.org/10.1177/15353702211027119DOI Listing
July 2021

Polyethylene Glycol Crowder's Effect on Enzyme Aggregation, Thermal Stability, and Residual Catalytic Activity.

Langmuir 2021 07 8;37(28):8474-8485. Epub 2021 Jul 8.

Nanostructured Materials Lab, University of Georgia, Athens, Georgia 30602, United States.

Protein stability and performance in various natural and artificial systems incorporating many other macromolecules for therapeutic, diagnostic, sensor, and biotechnological applications attract increasing interest with the expansion of these technologies. Here we address the catalytic activity of lysozyme protein (LYZ) in the presence of a polyethylene glycol (PEG) crowder in a broad range of concentrations and temperatures in aqueous solutions of two different molecular mass PEG samples ( = 3350 and 10000 g/mol). The phase behavior of PEG-protein solutions is examined by using dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS), while the enzyme denaturing is monitored by using an activity assay (AS) and circular dichroism (CD) spectroscopy. Molecular dynamic (MD) simulations are used to illustrate the effect of PEG concentration on protein stability at high temperatures. The results demonstrate that LYZ residual activity after 1 h incubation at 80 °C is improved from 15% up to 55% with the addition of PEG. The improvement is attributed to two underlying mechanisms. (i) Primarily, the stabilizing effect is due to the suppression of the enzyme aggregation because of the stronger PEG-protein interactions caused by the increased hydrophobicity of PEG and lysozyme at elevated temperatures. (ii) The MD simulations showed that the addition of PEG to some degree stabilizes the secondary structures of the enzyme by delaying unfolding at elevated temperatures. The more pronounced effect is observed with an increase in PEG concentration. This trend is consistent with CD and AS experimental results, where the thermal stability is strengthened with increasing of PEG concentration and molecular mass. The results show that the highest stabilizing effect is approached at the critical overlap concentration of PEG.
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http://dx.doi.org/10.1021/acs.langmuir.1c00872DOI Listing
July 2021

Effects of soy isoflavone supplementation on patients with diabetic nephropathy: a systematic review and meta-analysis of randomized controlled trials.

Food Funct 2021 Jul 8. Epub 2021 Jul 8.

Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM and Engineering & Technology Research Center for Chinese Materia Medica Quality of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou 510006, China.

Diabetic nephropathy (DN) is a microvascular complication that is becoming a worldwide public health concern. The aim of this study was to assess the effects of dietary soy isoflavone intervention on renal function and metabolic syndrome markers in DN patients. Seven databases including Medline, the Cochrane Central Register of Controlled Trials, Science Direct, Web of Science, Embase, China National Knowledge Infrastructure, and WanFang were searched for controlled trials that assessed the effects of soy isoflavone treatment in DN patients. Finally, a total of 141 patients from 7 randomized controlled trials were included. The meta-analysis showed that dietary soy isoflavones significantly decreased 24-hour urine protein, C-reactive protein (CRP), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose (FBG) in DN patients. The standard mean difference was -2.58 (95% CI: -3.94, -1.22; P = 0.0002) for 24-hour urine protein, -0.67 (95% CI: -0.94, -0.41; P < 0.00001) for BUN, -6.16 (95% CI: -9.02, -3.31; P < 0.0001) for CRP, -0.58 (95% CI: -0.83, -0.33; P < 0.00001) for TC, -0.41 (95% CI: -0.66, -0.16; P < 0.00001) for TG, -0.68 (95% CI: -0.94, -0.42; P < 0.00001) for LDL-C, and -0.39 (95% CI: -0.68, -0.10; P = 0.008) for FBG. Therefore, soy isoflavones may ameliorate DN by significantly decreasing 24-hour urine protein, BUN, CRP, TC, TG, LDL-C, and FBG.
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http://dx.doi.org/10.1039/d1fo01175hDOI Listing
July 2021

Plasma ceramides and cardiovascular events in hypertensive patients at high cardiovascular risk.

Am J Hypertens 2021 Jul 7. Epub 2021 Jul 7.

Key Laboratory of Cellular Physiology, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi Province, China.

Background: Plasma ceramides (Cer) have been used to evaluate risk of cardiovascular events in patients with coronary heart disease. We investigated the performance of ceramides and ceramide score (CERT) in hypertensive patients at high cardiovascular risk.

Methods: Seven ceramides were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry in 920 essential hypertension patients at high cardiovascular risk, who visited Beijing Anzhen Hospital from September 2016 to September 2018 (median age: 49 years, 562 males). All patients were followed up for Major Adverse Cardiovascular Events (MACE), which included incident acute coronary syndrome, heart failure, stroke, and cardiovascular death.

Results: During mean 2.3-year follow-up, 71 patients experienced MACE. Cer(d18:1/16:0), Cer(d18:1/22:0) and Cer(d18:1/24:0)were highly significant in predicting MACE [multiadjusted hazard ratios (HRs; 95% confidence interval) per standard deviation were 1.76 (1.34-2.30), 0.55 (0.41-0.73) and 0.66 (0.47-0.92),, respectively]. Compared with traditional variables (comprising presence of cardiovascular risk factors, hypertension-mediated organ damage, and comorbidities), a novel CERT for hypertensive patients (CERT-HBP), composed of Cer(d18:1/16:0), Cer(d18:1/24:1), and their ratios to Cer(d18:1/24:0) and Cer(d18:1/22:0) respectively, increased the C-statistic from 0.751 (95%CI, 0.697-0.806) to 0.791 (95%CI, 0.737-0.845), p=0.010. Net reclassification improvement and integrated discrimination improvement were 0.648 (95%CI, 0.421-0.885, p<0.001) and 0.046 (95%CI, 0.025-0.068, p<0.001), respectively.

Conclusions: A ceramide-based CERT-HBP was established to evaluate risk of MACE in hypertensive patients at high cardiovascular risk. This may improve identification of high-risk patients requiring increased attention and aggressive therapy.
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http://dx.doi.org/10.1093/ajh/hpab105DOI Listing
July 2021

[Advances in enrichment of phosphorylated peptides and glycopeptides by smart polymer-based materials].

Se Pu 2021 Jan;39(1):15-25

Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.

Protein post-translational modification (PTM) is at the forefront of focus of proteomics research. It not only regulates protein folding, state, activity, localization, and protein interactions, but also helps scientists understand the biological processes of organisms more comprehensively, providing stronger support and basis for the prediction, diagnosis, and treatment of diseases. In living organisms, there are more than 300 types of PTMs of proteins and their modification processes are dynamic. At the same time, protein modifications do not exist in isolation. The occurrence of the same physiological or pathological process requires the joint action of various modified proteins, which affect and coordinate with each other. Owing to the low abundance of PTM products (e. g., phosphorylated peptides or glycopeptides) and the presence of strong background interference, it is difficult to analyze them directly through mass spectrometry. Therefore, the development efficient materials and techniques for the selective enrichment of PTM peptides is urgently needed. Conventional separation methods have partially solved the challenges involved in the enrichment of glycopeptides and phosphorylated peptides; however, there are some inevitable issues, such as the excessive binding force of metal ions (e. g., Feand Ti) toward multiple phosphorylated peptides, resulting in difficulty in elution and identification through mass spectrometry. In addition, owing to the insufficient binding affinity of materials toward glycopeptides, most glycopeptides that have been identified at present are of the sialic acid type, and a large number of neutral glycans, for instance, -link glycopeptides and high mannose-type glycans are difficult to enrich and identify.The emergence of smart polymers provides a new avenue for the development of PTM-enriched materials. Several studies have reported that smart polymers can reversibly change their structure and function through external physical, chemical, or biological stimulation, to achieve highly controllable adsorption and desorption of phosphorylated peptides and glycopeptides. Based on this strategy, a series of novel enrichment materials and methods have been developed, which have greatly attracted the interest of researchers. On the one hand, the response changes of smart polymers include the increase or decrease of hydrophobicity, the change of shape and morphology, the redistribution of surface charge, the exposure or hiding of affinity ligands, etc. Changes in these properties can be achieved by simply changing external conditions such as temperature, pH, solvent polarity, and biomolecules. These properties, in turn, enable the fine-tuning of the affinity between the target and the smart polymers. Furthermore, the affinity can provide an additional driving force, which can significantly improve biological separation.On the other hand, smart polymers provide a series of convenient and expandable platforms for integrating various functional modules, such as specific recognition components, which will facilitate the development of novel enrichment materials for protein methylation, acetylation, and ubiquitination. Smart polymer materials show great potential in the field of separation, which is promising for the analysis and research of protein PTMs. This review summarizes the research progress of smart polymer materials for the separation and enrichment of phosphorylated peptides and glycopeptides according to nearly 50 representative articles from the Web of Science in the past two decades.
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http://dx.doi.org/10.3724/SP.J.1123.2020.05036DOI Listing
January 2021

War Against COVID-19: How Is National Identification Linked With the Adoption of Disease-Preventive Behaviors in China and the United States?

Polit Psychol 2021 Apr 26. Epub 2021 Apr 26.

The Chinese University of Hong Kong.

Fighting the COVID-19 pandemic requires large numbers of citizens to adopt disease-preventive practices. We contend that national identification can mobilize and motivate people to engage in preventive behaviors to protect the collective, which in return would heighten national identification further. To test these reciprocal links, we conducted studies in two countries with diverse national tactics toward curbing the pandemic: (1) a two-wave longitudinal survey in China (Study 1,  = 1200), where a national goal to fight COVID-19 was clearly set, and (2) a five-wave longitudinal survey in the United States (Study 2,  = 1001), where the national leader, President Trump, rejected the severity of COVID-19 in its early stage. Results revealed that national identification was associated with an increase in disease-preventive behaviors in both countries in general. However, higher national identification was associated with greater trust in Trump's administration among politically conservative American participants, which then was associated with slower adoption of preventive behaviors. The reciprocal effect of disease-preventive behaviors on national identification was observed only in China. Overall, our findings suggest that although national identification may serve as a protective factor in curbing the pandemic, this beneficial effect was reduced in some political contexts.

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http://dx.doi.org/10.1111/pops.12752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242506PMC
April 2021

tRNA-derived fragment tRF Lys-CTT-010 promotes triple-negative breast cancer progression by regulating glucose metabolism via G6PC.

Carcinogenesis 2021 Jul 3. Epub 2021 Jul 3.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

tRNA-derived fragments (tRFs) are a novel class of small non-coding RNAs (sncRNAs) whose biological roles are not well defined. Here, using multiple approaches, we investigated its role in human triple-negative breast cancer (TNBC). Our genome-wide transcriptome analysis of sncRNAs revealed that tRF Lys-CTT-010 was significantly increased in human TNBC. It promoted TNBC proliferation and migration. It also closely associated with starch and sucrose metabolism pathways (KEGG analysis) and positively regulated the expression of glucose-6-phosphatase catalytic subunit (G6PC), one of the related genes in the pathway. G6PC, a complex of glucose-6-phosphatase in gluconeogenesis and glycogenolysis, is upregulated in human TNBC samples. Further studies demonstrated that overexpression of G6PC in tRF Lys-CTT-010 inhibitor transfected TNBC cell lines can reverse malignant biological behavior and knockdown of G6PC in TNBC cell lines inhibited tumor progression and reversed the oncogenic function of tRF Lys-CTT-010. In addition, tRF Lys-CTT-010 interacted with G6PC to regulate cellular lactate production and glycogen consumption, resulting in cell survival and proliferation. Thus, fine-tuneing glucose metabolism and the tRF Lys-CTT-010 /G6PC axis may provide a therapeutic target for TNBC treatment.
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http://dx.doi.org/10.1093/carcin/bgab058DOI Listing
July 2021

SETD7-mediated monomethylation is enriched on soluble Tau in Alzheimer's disease.

Mol Neurodegener 2021 Jul 2;16(1):46. Epub 2021 Jul 2.

BioMed X Institute, Im Neuenheimer Feld 515, 69120, Heidelberg, Germany.

Background: Human tauopathies including Alzheimer's disease (AD) are characterized by alterations in the post-translational modification (PTM) pattern of Tau, which parallel the formation of insoluble Tau aggregates, neuronal dysfunction and degeneration. While PTMs on aggregated Tau have been studied in detail, much less is known about the modification patterns of soluble Tau. Furthermore, PTMs other than phosphorylation have only come into focus recently and are still understudied. Soluble Tau species are likely responsible for the spreading of pathology during disease progression and are currently being investigated as targets for immunotherapies. A better understanding of their biochemical properties is thus of high importance.

Methods: We used a mass spectrometry approach to characterize Tau PTMs on a detergent-soluble fraction of human AD and control brain tissue, which led to the discovery of novel lysine methylation events. We developed specific antibodies against Tau methylated at these sites and biochemically characterized methylated Tau species in extracts from human brain, the rTg4510 mouse model and in hiPSC-derived neurons.

Results: Our study demonstrates that methylated Tau levels increase with Tau pathology stage in human AD samples as well as in a mouse model of Tauopathy. Methylated Tau is enriched in soluble brain extracts and is not associated with hyperphosphorylated, high molecular weight Tau species. We also show that in hiPSC-derived neurons and mouse brain, methylated Tau preferentially localizes to the cell soma and nuclear fractions and is absent from neurites. Knock down and inhibitor studies supported by proteomics data led to the identification of SETD7 as a novel lysine methyltransferase for Tau. SETD7 specifically methylates Tau at K132, an event that facilitates subsequent methylation at K130.

Conclusions: Our findings indicate that methylated Tau has a specific somatic and nuclear localization, suggesting that the methylation of soluble Tau species may provide a signal for their translocation to different subcellular compartments. Since the mislocalization and depletion of Tau from axons is associated with tauopathies, our findings may shed light onto this disease-associated phenomenon.
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http://dx.doi.org/10.1186/s13024-021-00468-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254302PMC
July 2021
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