Publications by authors named "Haitao Li"

627 Publications

PRMT1-mediated H4R3me2a recruits SMARCA4 to promote colorectal cancer progression by enhancing EGFR signaling.

Genome Med 2021 Apr 14;13(1):58. Epub 2021 Apr 14.

The State Key Laboratory of Pharmaceutical Biotechnology, Department of Hematology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, China-Australia Institute of Translational Medicine, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China.

Background: Aberrant changes in epigenetic mechanisms such as histone modifications play an important role in cancer progression. PRMT1 which triggers asymmetric dimethylation of histone H4 on arginine 3 (H4R3me2a) is upregulated in human colorectal cancer (CRC) and is essential for cell proliferation. However, how this dysregulated modification might contribute to malignant transitions of CRC remains poorly understood.

Methods: In this study, we integrated biochemical assays including protein interaction studies and chromatin immunoprecipitation (ChIP), cellular analysis including cell viability, proliferation, colony formation, and migration assays, clinical sample analysis, microarray experiments, and ChIP-Seq data to investigate the potential genomic recognition pattern of H4R3me2s in CRC cells and its effect on CRC progression.

Results: We show that PRMT1 and SMARCA4, an ATPase subunit of the SWI/SNF chromatin remodeling complex, act cooperatively to promote colorectal cancer (CRC) progression. We find that SMARCA4 is a novel effector molecule of PRMT1-mediated H4R3me2a. Mechanistically, we show that H4R3me2a directly recruited SMARCA4 to promote the proliferative, colony-formative, and migratory abilities of CRC cells by enhancing EGFR signaling. We found that EGFR and TNS4 were major direct downstream transcriptional targets of PRMT1 and SMARCA4 in colon cells, and acted in a PRMT1 methyltransferase activity-dependent manner to promote CRC cell proliferation. In vivo, knockdown or inhibition of PRMT1 profoundly attenuated the growth of CRC cells in the C57BL/6 J-Apc CRC mice model. Importantly, elevated expression of PRMT1 or SMARCA4 in CRC patients were positively correlated with expression of EGFR and TNS4, and CRC patients had shorter overall survival. These findings reveal a critical interplay between epigenetic and transcriptional control during CRC progression, suggesting that SMARCA4 is a novel key epigenetic modulator of CRC. Our findings thus highlight PRMT1/SMARCA4 inhibition as a potential therapeutic intervention strategy for CRC.

Conclusion: PRMT1-mediated H4R3me2a recruits SMARCA4, which promotes colorectal cancer progression by enhancing EGFR signaling.
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http://dx.doi.org/10.1186/s13073-021-00871-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048298PMC
April 2021

A conserved BAH module within mammalian BAHD1 connects H3K27me3 to Polycomb gene silencing.

Nucleic Acids Res 2021 Apr 6. Epub 2021 Apr 6.

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.

Trimethylation of histone H3 lysine 27 (H3K27me3) is important for gene silencing and imprinting, (epi)genome organization and organismal development. In a prevalent model, the functional readout of H3K27me3 in mammalian cells is achieved through the H3K27me3-recognizing chromodomain harbored within the chromobox (CBX) component of canonical Polycomb repressive complex 1 (cPRC1), which induces chromatin compaction and gene repression. Here, we report that binding of H3K27me3 by a Bromo Adjacent Homology (BAH) domain harbored within BAH domain-containing protein 1 (BAHD1) is required for overall BAHD1 targeting to chromatin and for optimal repression of the H3K27me3-demarcated genes in mammalian cells. Disruption of direct interaction between BAHD1BAH and H3K27me3 by point mutagenesis leads to chromatin remodeling, notably, increased histone acetylation, at its Polycomb gene targets. Mice carrying an H3K27me3-interaction-defective mutation of Bahd1BAH causes marked embryonic lethality, showing a requirement of this pathway for normal development. Altogether, this work demonstrates an H3K27me3-initiated signaling cascade that operates through a conserved BAH 'reader' module within BAHD1 in mammals.
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http://dx.doi.org/10.1093/nar/gkab210DOI Listing
April 2021

Distal anastomosis support for bypass grafting with coronary endarterectomy for the severe diseased posterior descending artery.

Perfusion 2021 Mar 24:267659120988811. Epub 2021 Mar 24.

Department of Cardiac Surgery, Beijing An Zhen Hospital of Capital Medical University, Beijing, People's Republic of China.

Background: The posterior descending artery is the most common vessel chosen for an endarterectomy, while endarterectomy to the posterior descending artery is associated with decreased graft patency. The purpose of this study was to describe a distal anastomosis support (DAS) technique and retrospectively investigate the effect of DAS on the mid-term graft patency.

Methods: Between January 2016 and December 2018, 200 patients with a PDA severe lesion who underwent off-pump coronary artery bypass (OPCAB) with CE (OPCAB + CE group,  = 95) and OPCAB + CE with DAS for anastomosis of PDA grafted by saphenous vein (SVG) (OPCAB + CE + DAS group,  = 105) were evaluated retrospectively. All patients came back to follow-up visit 6th, 12th, 24th, and 36th postoperative month. The primary endpoint is the graft failure (FitzGibbon B or O) of SVG-PDA on the follow-up CTA or CAG.

Results: There was no significant difference in perioperative outcomes. We found significantly improved cumulative graft patency in OPCAB + CE + DAS group at 36 months after operation (84.6% vs 76.5%, p = 0.02). In multivariate Cox regression analysis, plaque length larger than 2 cm (hazard ratio [HR], 13.108, 95% confidence interval [CI], 2.842-60.457, p = 0.001), and peak TNI ⩾70× ULN within 48 hours of surgery (HR, 3.778, 95% CI, 1.453-9.823, p = 0.006) were independent predictors of graft failure, whereas PDA diameter greater than 1.5 mm (HR, 0.231, 95% CI, 0.081-0.654, p = 0.006), and DAS use (HR, 0.336, 95% CI, 0.139-0.812, p = 0.015) were significant protective factors.

Conclusions: Concomitant DAS conferred superior mid-term patency of SVG-PDA. Adding the DAS procedure to OPCAB + CE may be a promising surgical option for patients with a PDA severe lesion, especially when PDA diameter less than 1.5 mm and plaque length greater than 2 cm.
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http://dx.doi.org/10.1177/0267659120988811DOI Listing
March 2021

Shining light on cardiac electrophysiology: From detection to intervention, from basic research to translational applications.

Life Sci 2021 Jun 15;274:119357. Epub 2021 Mar 15.

Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China. Electronic address:

Cardiac arrhythmias are an important group of cardiovascular diseases, which can occur alone or in association with other cardiovascular diseases. The development of cardiac arrhythmias cannot be separated from changes in cardiac electrophysiology, and the investigation and clarification of cardiac electrophysiological changes are beneficial for the treatment of cardiac arrhythmias. However, electrical energy-based pacemakers and defibrillators, which are widely used to treat arrhythmias, still have certain disadvantages. Thereby, optics promises to be used for optical manipulation and its use in biomedicine is increasing. Since visible light is readily absorbed and scattered in living tissues and tissue penetration is shallow, optical modulation for cells and tissues requires conversion media that convert light energy into bioelectrical activity. In this regard, fluorescent dyes, light-sensitive ion channels, and optical nanomaterials can assume this role, the corresponding optical mapping technology, optogenetics technology, and optical systems based on luminescent nanomaterials have been introduced into the research in cardiovascular field and are expected to be new tools for the study and treatment of cardiac arrhythmias. In addition, infrared and near-infrared light has strong tissue penetration, which is one of the excellent options of external trigger for achieving optical modulation, and is also widely used in the study of optical modulation of biological activities. Here, the advantages of optical applications are summarized, the research progresses and emerging applications of optical-based technologies as detection and intervention tools for cardiac electrophysiological are highlighted. Moreover, the prospects for future applications of optics in clinical diagnosis and treatment are discussed.
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http://dx.doi.org/10.1016/j.lfs.2021.119357DOI Listing
June 2021

Dysregulation of exosomal miR-192 and miR-194 expression in lung adenocarcinoma patients.

Saudi J Biol Sci 2021 Mar 20;28(3):1561-1568. Epub 2021 Jan 20.

Biotechnology Center, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.

Non-small cell lung cancer (NSCLC) is the main reason of cancer linked mortality and around 80% of cases diagnosed in advanced stage. Therefore current study designed to evaluate the deregulation of miRNA-194 and miRNA-192 in different body fluid of Non small cell lung cancer participants. Present study recruited newly diagnosed histopathologically confirmed. It was observed that the 40% NSCLC participants showed elevated miR-194 expression and 60% NSCLC participants showed reduced miR-194 expression in serum sample while in Bronchial wash, only 20% NSCLC participants showed elevated miR-194 expression while 80% showed reduced miR-194 expression (p = 0.003). It was found that the 54% NSCLC participants showed elevated miR-192 expression and 55% NSCLC participants showed reduced miR-192 expression in serum sample while In Bronchial wash sample, only 25% NSCLC participants showed high miR-192 expression while 75% showed low miR-192 expression (P = 0.0004). Expression of miR-194 was significantly associated with TNM stages (p < 0.0001, p < 0.0001), distant organ metastases (p < 0.0001, p < 0.0001), pathological grade (p = 0.0009, p = 0.0005) among serum sample and bronchial wash sample. Same observation was found with expression of miR-192 and it was significantly associated with TNM stages (p < 0.0001, p < 0.0001), distant organ metastases (p < 0.0001, p < 0.0001), pathological grade (p = 0.006, p = 0.001) among serum sample and bronchial wash sample. It was observed that the NSCLC participants who had high serum based miR-194 expression showed 22 months of overall median survival while low expression of serum based miR-194 expression showed 18 months of overall median survival. Present study suggests that decreased expression of miR-194 and miR-192 was significantly associated with different clinical features of NSCLC cases. However, significantly higher number of NSCLC cases showed low expression of miR-194 and miR-192 in bronchial lavage sample. Decreased poor overall survival was found to be associated with bronchial wash sample with respect to low miR-194 and miR-192 expression while NSCLC participants showed better overall survival with high miR-194 and miR-192 expression. This suggested decreased expression of miR-192 and miR-194 expression could be the potential prognostic marker among NSCLC participants.
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http://dx.doi.org/10.1016/j.sjbs.2021.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938118PMC
March 2021

A catalytic dependent role for DNMT3B in tumor suppression.

EBioMedicine 2021 Mar 11;65:103237. Epub 2021 Mar 11.

Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA. Electronic address:

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http://dx.doi.org/10.1016/j.ebiom.2021.103237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966975PMC
March 2021

Transcriptome Analysis Reveals the Genes Involved in FGSZY16M3 Biofilm Formation.

Microorganisms 2021 Feb 14;9(2). Epub 2021 Feb 14.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

Biofilm formation has evolved as an adaptive strategy for bacteria to cope with harsh environmental conditions. Currently, little is known about the molecular mechanisms of biofilm formation in bifidobacteria. A time series transcriptome sequencing analysis of both biofilm and planktonic cells of FGSZY16M3 was performed to identify candidate genes involved in biofilm formation. Protein-protein interaction network analysis of 1296 differentially expressed genes during biofilm formation yielded 15 clusters of highly interconnected nodes, indicating that genes related to the SOS response (, , , , , , and ) associated with the early stage of biofilm formation. Genes involved in extracellular polymeric substances were upregulated (, , , , , , , , and ) in the stage of biofilm maturation. To further investigate the genes related to biofilm formation, weighted gene co-expression network analysis (WGCNA) was performed with 2032 transcript genes, leading to the identification of nine WGCNA modules and 133 genes associated with response to stress, regulation of gene expression, quorum sensing, and two-component system. These results indicate that biofilm formation in is a multifactorial process, involving stress response, structural development, and regulatory processes.
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http://dx.doi.org/10.3390/microorganisms9020385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917626PMC
February 2021

Comparison of the management and control of hypertension by public and private primary care providers in Shenzhen, China.

Heliyon 2021 Feb 17;7(2):e06280. Epub 2021 Feb 17.

Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, China.

Background: The Chinese government has designated primary care as the cornerstone for addressing the public health challenges posed by hypertension. In urban China, primary care is usually delivered by either publicly- or privately-owned community health centers (CHCs), and whether there CHCs can achieve the same population health objectives remains unknown. This study aimed to compare management and control of hypertension by public versus private primary care providers.

Methods: A face-to-face, cross-sectional patient survey was performed on-site at 12 CHCs in Shenzhen, China (3 privately owned and 9 publicly owned). A total of 1046 hypertensive patients were selected via systematic sampling methods and completed the survey. Information regarding primary care management, anti-hypertensive drug treatment and compliance, and blood pressure was recorded.

Results: Compared with hypertensive patients enrolled from private CHCs, those from public CHCs were more likely to be managed by CHCs (84.6% vs. 61.6%; odds ratio [OR] = 2.594, 95% confidence interval [CI]: 1.730-3.891), to take anti-hypertensive drugs (87.5% vs. 66.8%; OR = 3.193, 95%CI: 1.995-5.110), and to adhere to physicians' advice (91.5% vs. 82.5%; OR = 1.930, 95%CI: 1.0002-3.717). However, hypertension control rates did not differ significantly between public and private CHCs (48.3% vs. 37.6%; > 0.01, tested by multiple logistic regression models).

Conclusions: Public CHCs showed better performance for the management of hypertensive patients compared with private CHCs, although there is room for improvements for both types of CHCs. Initiation of interventions to motivate primary care providers in both public and private CHCs to comply with hypertension management guidelines is recommended.
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http://dx.doi.org/10.1016/j.heliyon.2021.e06280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902539PMC
February 2021

Effects of Taraxacum and Astragalus extracts combined with probiotic Bacillus subtilis and Lactobacillus on Escherichia coli-infected broiler chickens.

Poult Sci 2021 Apr 16;100(4):101007. Epub 2021 Jan 16.

Department of Animal Medicine, Agricultural College of Yanbian University, Yanji, Jilin 133002, China. Electronic address:

Diarrhea caused by Escherichia coli (E. coli) is one of the most common diseases that affects the growth and development of poultry. This study was conducted to investigate the synergistic effects of traditional Chinese medicine (TCM) combined with probiotics against E. coli infection and its mechanism in broiler chickens. The optimal proportion formula TCM and probiotics was screened by orthogonal test and range analysis method; the in vitro antibacterial activity was based on the Oxford cup method. Isolated pathogenic E. coli was injected subcutaneously into the neck of the broilers to establish an E. coli-infected model. The broilers were administrated with drugs in drinking water daily for 7 d before and after E. coli infection. The diarrhea rate, mortality, body weight (BW) gain, feed intake, immune organ index, intestinal and hepatic histopathological changes were monitored. The expression of IL-2, IL-10, and TLR-4 mRNA in the intestinal tissues was measured by RT-PCR. Our results showed that the optimal proportion formula of Taraxacum extracts: total flavonoids of Astragalus: polysaccharides of Astragalus: probiotics was 5: 2: 2: 2; TCM combined with probiotics was highly sensitive to E. coli. TCM combined with probiotics synergistically increased BW gain, decreased the diarrhea rate and mortality of broilers, alleviated intestinal and hepatic pathological changes, accompanied by the increase of IL-2 and IL-10 mRNA expression and the inhibition of TLR-4 mRNA expression. It suggests that the combination of TCM and probiotics may produce a synergistic protective effect against E. coli infection by improving the indicators of diarrhea and regulating the expression of IL-2, IL-10, and TLR-4 mRNA in broiler chickens. The synergistic interactions between TCM and probiotics represent a promising strategy for the treatment of E. coli infection.
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http://dx.doi.org/10.1016/j.psj.2021.01.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921871PMC
April 2021

Lipid metabolism changes in patients with severe COVID-19.

Clin Chim Acta 2021 Feb 24;517:66-73. Epub 2021 Feb 24.

Department of Respiratory and Critical Care Medicine, Central South University, Changsha 410008, China. Electronic address:

Background: We investigated the dynamic changes in lipid profiles and their correlations with disease severity and clinical outcome in patients with severe COVID-19.

Methods: We retrospectively reviewed 519 severe COVID-19 patients with confirmed outcomes (discharged or deceased), admitted to the West Court of Union Hospital in Wuhan, China, between 29 January and 8 April 2020.

Results: Altogether, 424 severe COVID-19 patients, including 34 non-survivors and 390 survivors, were included in the final analyses. During hospitalization, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) showed an increasing trend in survivors, but showed a downward trend in non-survivors. The serum concentrations of HDL-C and apoA-I were inversely correlated with C-reactive protein (CRP), length of hospital stay of survivors, and disease severity scores. For in-hospital deaths, the areas under the receiver operating characteristic curves (AUCs) of the ratios of CRP/HDL-C and CRP/apoA-I at admission were 0.84 and 0.83, respectively. Moreover, patients with high ratios of CRP/HDL-C (>77.39) or CRP/apoA-I (>72.37) had higher mortality rates during hospitalization (log-rank p < 0.001). Logistic regression analysis demonstrated that hypertension, lactate dehydrogenase, SOFA score, and High CRP/HDL-C ratio were independent predictors of in-hospital mortality.

Conclusions: During severe COVID-19, HDL-C and apoA-I concentrations are dramatically decreased in non-survivors. Moreover, High CRP/HDL-C ratio is significantly associated with an increase in mortality and a poor prognosis.
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http://dx.doi.org/10.1016/j.cca.2021.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903909PMC
February 2021

Simultaneous sensing of cysteine/homocysteine and glutathione with a fluorescent probe based on a single atom replacement strategy.

Anal Methods 2021 03 26;13(11):1358-1363. Epub 2021 Feb 26.

Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, China.

In recent years, there have been many reports of fluorescent probes for multi-channel detection of Cys, Hcy and GSH. Particularly, reports of fluorescent probes using NBD (7-nitro-1,2,3-benzoxadiazole) or SNBD (7-nitro-1,2,3-benzothiadiazole) moieties as fluorophores are particularly common. Unfortunately, their 4-sulfhydryl derivatives exhibited negligible fluorescence, which makes them incapable of detecting GSH directly. Herein, by performing single selenium-for-oxygen atom replacement within 4-chloro-substituted NBD (NBD-Cl), we developed a small molecule fluorescent probe based on a single atom replacement strategy, which enables the probe to be used for simultaneously distinguishing Cys/Hcy and GSH, along with fluorescence imaging of Cys/Hcy and GSH in live cells from red and green emission channels, respectively.
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http://dx.doi.org/10.1039/d0ay02206cDOI Listing
March 2021

Distribution and potential provenance of trace elements in a 120-year dated sediment core from west Daya Bay, northeastern South China Sea.

Mar Pollut Bull 2021 Mar 19;164:112032. Epub 2021 Feb 19.

Guangdong Provincial Key Laboratory of Emergency Test for Dangerous Chemicals, Guangdong Institute of Analysis, Guangzhou 510070, PR China. Electronic address:

Eighteen trace elements were analyzed in a 120-year sediment core from Daya Bay. Burial flux history and potential provenance, the relationships among trace elements, and biogenic compositions were analyzed for determining the trend and extent of trace element accumulation and identifying corresponding anthropogenic effects. Additionally, the effects of anthropogenic activities on Daya Bay were reconstructed, and a baseline/background estimation was provided for Daya Bay. The burial fluxes of V, Cr, Cd, Cu, Zn, Mn, Fe, Co, Ni, Pb, Hg, Zn, Mo, Ag, As, Se, and Tl increased from 1960 to 2010, especially after the late 1980s. Our results are useful for understanding pollution and land-sea interactions along the coasts of the South China Sea, especially in the Guangdong-Hong Kong-Macao Greater Bay Area.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112032DOI Listing
March 2021

Incorporating accident liability into crash risk analysis: A multidimensional risk source approach.

Accid Anal Prev 2021 Apr 16;153:106035. Epub 2021 Feb 16.

Department of Transportation, Jilin University, Changchun, 130022, China.

In the field of traffic safety, the occurrence of accidents remains a cause of concern for road regulators as well as users. Exploring risk factors inducing the accidents and quantifying the accident risk will not only benefit the prevention and control of traffic accidents but also assist in developing effective risk propagation model for road accidents. This study uses detailed accident record data to mine the risk factors affecting the occurrence of accidents, and quantify the accident risk under the combination of risk factors. First, by reviewing relevant literature and analyzing historical accident, we construct a multi-dimension characterization framework of risk factors with bi-level structure. The Human Factors Analysis and Classification System (HFACS) is applied to supplement and improve the framework. Next, under this framework, we identify the risk factors in traffic accident record, and analyze the statistical characteristics from the level of risk sources and risk characteristics. Then, the concept of accident liability weight is proposed to measure the impact of risk factors on accident occurrence. Through the liability affirmation of risk factors, the accident probability are updated. Last, we establish an accident risk quantify model (ARQM) based on the mean mutual information to compare the likelihood of accidents in different scenarios. In addition, we compare the accident probability and risk under equivalent liability and liability affirmation, as well as give some fundamental ideas regarding how to effectively prevent accidents.
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http://dx.doi.org/10.1016/j.aap.2021.106035DOI Listing
April 2021

Turn-on fluorescent probe for sensing exogenous and endogenous hypochlorous acid in living cells, zebrafishes and mice.

Talanta 2021 Apr 28;225:122030. Epub 2020 Dec 28.

Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, China. Electronic address:

Hypochlorous acid (HOCl), belonging to biologically significant reactive oxygen species (ROS), plays crucial roles in many biological and pathological processes. It is of great value to explore fluorescent probes for the image of hypochlorous acid in various biological environments. We herein reported a novel fluorescent probe HN-ClO for monitoring HOCl with moderate water-solubility, good photostability, high fluorescence quantum yield and large Stokes shift. This probe exhibited excellent selectivity and high sensitivity to sense HOCl. Furthermore, probe HN-ClO was successfully applied to monitor endogenous and exogenous HOCl in living cells, zebrafishes and mice, and possessed the potential to further explore the physiological and pathological roles of hypochlorous acid in biological systems.
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http://dx.doi.org/10.1016/j.talanta.2020.122030DOI Listing
April 2021

HDAC9 Silencing Exerts Neuroprotection Against Ischemic Brain Injury miR-20a-Dependent Downregulation of NeuroD1.

Front Cell Neurosci 2020 11;14:544285. Epub 2021 Jan 11.

Department of Neurosurgery, Shandong Provincial Hospital, Jinan, China.

Cerebral stroke is an acute cerebrovascular disease that is a leading cause of death and disability worldwide. Stroke includes ischemic stroke and hemorrhagic strokes, of which the incidence of ischemic stroke accounts for 60-70% of the total number of strokes. Existing preclinical evidence suggests that inhibitors of histone deacetylases (HDACs) are a promising therapeutic intervention for stroke. In this study, the purpose was to investigate the possible effect of HDAC9 on ischemic brain injury, with the underlying mechanism related to microRNA-20a (miR-20a)/neurogenic differentiation 1 (NeuroD1) explored. The expression of HDAC9 was first detected in the constructed middle cerebral artery occlusion (MCAO)-provoked mouse model and oxygen-glucose deprivation (OGD)-induced cell model. Next, primary neuronal apoptosis, expression of apoptosis-related factors (Bax, cleaved caspase3 and bcl-2), LDH leakage rate, as well as the release of inflammatory factors (TNF-α, IL-1β, and IL-6) were evaluated by assays of TUNEL, Western blot, and ELISA. The relationships among HDAC9, miR-20a, and NeuroD1 were validated by analysis and ChIP assay. HDAC9 was highly-expressed in MCAO mice and OGD-stimulated cells. Silencing of HDAC9 inhibited neuronal apoptosis and inflammatory factor release . HDAC9 downregulated miR-20a by enriching in its promoter region, while silencing of HDCA9 promoted miR-20a expression. miR-20a targeted Neurod1 and down-regulated its expression. Silencing of HDAC9 diminished OGD-induced neuronal apoptosis and inflammatory factor release as well as ischemic brain injury by regulating the miR-20a/NeuroD1 signaling. Overall, our study revealed that HDAC9 silencing could retard ischemic brain injury through the miR-20a/Neurod1 signaling.
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http://dx.doi.org/10.3389/fncel.2020.544285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873949PMC
January 2021

Histone H3Q5 serotonylation stabilizes H3K4 methylation and potentiates its readout.

Proc Natl Acad Sci U S A 2021 Feb;118(6)

Ministry of Education Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China;

Serotonylation of glutamine 5 on histone H3 (H3Q5ser) was recently identified as a permissive posttranslational modification that coexists with adjacent lysine 4 trimethylation (H3K4me3). While the resulting dual modification, H3K4me3Q5ser, is enriched at regions of active gene expression in serotonergic neurons, the molecular outcome underlying H3K4me3-H3Q5ser crosstalk remains largely unexplored. Herein, we examine the impact of H3Q5ser on the readers, writers, and erasers of H3K4me3. All tested H3K4me3 readers retain binding to the H3K4me3Q5ser dual modification. Of note, the PHD finger of TAF3 favors H3K4me3Q5ser, and this binding preference is dependent on the Q5ser modification regardless of H3K4 methylation states. While the activity of the H3K4 methyltransferase, MLL1, is unaffected by H3Q5ser, the corresponding H3K4me3/2 erasers, KDM5B/C and LSD1, are profoundly inhibited by the presence of the mark. Collectively, this work suggests that adjacent H3Q5ser potentiates H3K4me3 function by either stabilizing H3K4me3 from dynamic turnover or enhancing its physical readout by downstream effectors, thereby potentially providing a mechanism for fine-tuning critical gene expression programs.
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http://dx.doi.org/10.1073/pnas.2016742118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017887PMC
February 2021

Missing for partnership: understanding nucleosomal de novo DNA cytosine methylation by a spliced DNMT3 complex.

Authors:
Min Zhang Haitao Li

Signal Transduct Target Ther 2021 Jan 29;6(1):36. Epub 2021 Jan 29.

MOE Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, China.

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http://dx.doi.org/10.1038/s41392-021-00461-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846833PMC
January 2021

Optimal Strategy Estimation of Random Evolutionary Boolean Games.

IEEE Trans Cybern 2021 Jan 29;PP. Epub 2021 Jan 29.

The optimal strategy estimation of random evolutionary Boolean games (REBGs) is discussed in this article. First, using the minimum mean square error criterion, the optimal strategy estimator is proposed for REBGs. Then, a matrix approach is developed to calculate the optimal strategy estimator by the aid of a semitensor product of matrices, which includes the prediction matrix, updating distribution, and strategy iterative formula. Finally, an elucidative example is included to show the obtained results are valid.
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http://dx.doi.org/10.1109/TCYB.2021.3050192DOI Listing
January 2021

[Construction and identification of an infectious clone for CDV-3 strain of canine distemper virus].

Sheng Wu Gong Cheng Xue Bao 2021 Jan;37(1):178-186

Institute of Special Wild Economic Animal and Plant Science, Chinese Academy of Agricultural Sciences, Changchun 130122, Jilin, China.

In order to establish an infectious clone for CDV-3, a commercial vaccine strain of canine distemper virus for mink, to provide reference for the studies of pathogenesis and novel vaccine development of CDV. Thirteen pairs of primers were used to amplify the full-length genome of CDV-3 strain. Five long fragments were obtained based on single restriction site analysis of the whole genome of CDV-3 by RT-PCR. Five fragments were successively inserted into the multiple clone sites in the modified eukaryotic vector of pcDNA3.2 by restriction enzymes and splicing. Meanwhile, the hammerhead ribozyme and hepatitis delta virus ribozyme sequences were added to the beginning of F1 fragment and the ending of F5 fragment, respectively. Then, the full-length cDNA recombinant plasmid of CDV-3 was obtained and named as pcDNA3.2-CDV-3. In addition, three helper plasmids, expressing the N protein, P protein and L protein of the CDV-3 strain respectively, were constructed. The 293T cells were transfected with the full-length cDNA recombinant plasmid and three helper plasmids by Lipofectamine™ 2000. At 3 days post transfection, the supernatant was added to the monolayer of Vero cells to observe the typical syncytium of CDV. Indirect immunofluorescence and artificial label identification of recombinant virus rCDV-3 were conducted after the occurrence of lesions. Finally, the growth characteristics of wtCDV-3 and rCDV-3 were compared after passaging of rCDV-3. The identification of the full-length cDNA recombinant plasmid and three helper plasmids by restriction enzyme digestion and sequencing were consistent with expected. The Vero cells infected with the recombinant rCDV-3 showed typical syncytic. The identification of indirect immunofluorescence and labeled marker, and observation under electron microscope proved that the rCDV-3 was indeed rescued from the recombinant plasmid of pcDNA3.2-CDV-3. In comparison of the virus titers of wtCDV-3, rCDV-3 replicated massively and rapidly and reached the maximize virus titer of 10⁷·⁶⁶⁷ TCID₅₀/mL within 36 h post infection (p.i.) in Vero cells, while wtCDV-3 grew gradually to 10⁶·⁶⁶⁷ TCID₅₀/mL at 72 h p.i. in Vero cells. This reverse genetic system of CDV-3 strain has been established successfully, to provide reference for the studies of pathogenesis and novel vaccine development of CDV.
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http://dx.doi.org/10.13345/j.cjb.200248DOI Listing
January 2021

Classification of Mild Cognitive Impairment with Multimodal Data using both Labeled and Unlabeled Samples.

IEEE/ACM Trans Comput Biol Bioinform 2021 Jan 20;PP. Epub 2021 Jan 20.

Mild Cognitive Impairment (MCI) is a preclinical stage of Alzheimer's Disease (AD) and is clinical heterogeneity. The classification of MCI is crucial for the early diagnosis and treatment of AD. In this study, we investigated the potential of using both labeled and unlabeled samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort to classify MCI through the multimodal co-training method. We utilized both structural magnetic resonance imaging (sMRI) data and genotype data of 364 MCI samples including 228 labeled and 136 unlabeled MCI samples from the ADNI-1 cohort. First, the selected quantitative trait (QT) features from sMRI data and SNP features from genotype data were used to build two initial classifiers on 228 labeled MCI samples. Then, the co-training method was implemented to obtain new labeled samples from 136 unlabeled MCI samples. Finally, the random forest algorithm was used to obtain a combined classifier to classify MCI patients in the independent ADNI-2 dataset. The experimental results showed that our proposed framework obtains an accuracy of 85.50% and an AUC of 0.825 for MCI classification, respectively, which showed that the combined utilization of sMRI and SNP data through the co-training method could significantly improve the performances of MCI classification.
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http://dx.doi.org/10.1109/TCBB.2021.3053061DOI Listing
January 2021

Multiple microarray analyses identify key genes associated with the development of Non-Small Cell Lung Cancer from Chronic Obstructive Pulmonary Disease.

J Cancer 2021 1;12(4):996-1010. Epub 2021 Jan 1.

Thoracic Medicine Department 1, Hunan Cancer Hospital, Changsha, Hunan Province, P.R. China, 410013.

Chronic obstructive pulmonary disease (COPD) is an independent risk factor of non-small cell lung cancer (NSCLC). This study aimed to analyze the key genes and potential molecular mechanisms that are involved in the development from COPD to NSCLC. Expression profiles of COPD and NSCLC in GSE106899, GSE12472, and GSE12428 were downloaded from the Gene Expression Omnibus (GEO) database, followed by identification of the differentially expressed genes (DEGs) between COPD and NSCLC. Based on the identified DEGs, functional pathway enrichment and lung carcinogenesis-related networks analyses were performed and further visualized with Cytoscape software. Then, principal component analysis (PCA), cluster analysis, and support vector machines (SVM) verified the ability of the top modular genes to distinguish COPD from NSCLC. Additionally, the corrections between these key genes and clinical staging of NSCLC were studied using the UALCAN and HPA websites. Finally, a prognostic risk model was constructed based on multivariate Cox regression analysis. Kaplan-Meier survival curves of the top modular genes on the training and verification sets were generated. A total of 2350, 1914, and 1850 DEGs were obtained from GSE106899, GSE12472, and GSE12428 datasets, respectively. Following analysis of protein-protein interaction networks, the identified modular gene signatures containing H2AFX, MCM2, MCM3, MCM7, POLD1, and RPA1 were identified as markers for discrimination between COPD and NSCLC. The modular gene signatures were mainly enriched in the processes of DNA replication, cell cycle, mismatch repair, and others. Besides, the expression levels of these genes were significantly higher in NSCLC than in COPD, which was further verified by the immunohistochemistry. In addition, the high expression levels of H2AFX, MCM2, MCM7, and POLD1 correlate with poor prognosis of lung adenocarcinoma (LUAD). The Cox regression prognostic risk model showed the similar results and the predictive ability of this model is independent of other clinical variables. This study revealed several key modules that closely relate to NSCLC with underlying disease COPD, which provide a deeper understanding of the potential mechanisms underlying the malignant development from COPD to NSCLC. This study provides valuable prognostic factors in high-risk lung cancer patients with COPD.
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http://dx.doi.org/10.7150/jca.51264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797649PMC
January 2021

Distinct Impacts of Pre-Operative Antiviral Treatment on Post-Operative Outcomes of HBV-related Hepatocellular Carcinoma: A Landmark Analysis.

J Cancer 2021 1;12(1):170-180. Epub 2021 Jan 1.

Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.

The effect of anti-viral treatment (AVT) initiated before surgery (pre-operative AVT) on HBV-related hepatocellular carcinoma (HCC) has been controversial. This study aimed to elucidate the prognostic significance of pre-operative AVT for HCC patients who received hepatectomy. A large-scale retrospective study was conducted based on a cohort consisting of 1937 HBV-related HCC patients who underwent R0 liver resection between January 2011 and December 2012. Propensity score matching (PSM) method was adopted to balance covariates and landmark survival analyses were performed to visualize effects in different phases after surgery. After PSM, a total of matched 744 patients (372 in each group) were recruited. The patients in the pre-operative AVT group had lower HBV-DNA loading levels and better recurrence-free survival (RFS) than those in the non-AVT group. The 1, 3, 5-year RFS rates of two groups were 67.3%, 49.0%, and 43.1% vs. 66.7%, 41.1% and 18.5%, respectively (0.001). Landmark survival analyses demonstrated that pre-operative AVT could improve RFS, and the effect was beginning to show after the first 12 months. There was no significant difference of overall survival (OS) between the two groups (0.543), and the landmark survival analyses indicated that pre-operative AVT could improve OS and this effect was beginning to show after 36 months. Additionally, multivariate Cox regression analyses revealed that larger tumor (>5cm), esophageal and gastric varices, lymph node metastasis were independent risk factors of RFS, and larger tumor (>5cm) and ascites were independent risk factors of OS. Pre-operative AVT could significantly improve the RFS, and could not improve short-term OS (< 36 months) but could better long-term survival of the patients with HBV-HCC after surgery.
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http://dx.doi.org/10.7150/jca.47125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738838PMC
January 2021

Myocardial infarction biomarker C-reactive protein detection on nanocomposite aptasensor.

Biotechnol Appl Biochem 2020 Dec 28. Epub 2020 Dec 28.

Department of Third Emergency, Baoding First Central Hospital West Hospital, Baoding, Hebei, People's Republic of China.

Myocardial infarction (MI) is considered as one of the major life-threatening health issues worldwide. Growing number of cases every year is demanding rapid, portable, and early detection by the sensing devices for the identification of MI. This research work introduces a modified interdigitated electrode (IDE) sensing surface constructed with single-walled carbon nanotube (SWCN) to detect the cardiac biomarker, C-reactive protein (CRP). CRP-specific aptamer was conjugated with gold nanoparticle and attached on SWCN-constructed IDE surface. This probe-modified sensing surface has reached the limit of CRP detection to 10 pM on a linear regression curve with the regression coefficient of R² = 0.9223 [y = 0.9198x - 0.4326]. Further, control molecules, such as random aptamer sequence and nontarget cardiac biomarker (Troponin I), did not show the current response, indicating the specific CRP detection. This sensing strategy helps to detect the lower level of CRP and diagnose the MI at its earlier stages.
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http://dx.doi.org/10.1002/bab.2093DOI Listing
December 2020

Selective Targeting of AF9 YEATS Domain by Cyclopeptide Inhibitors with Preorganized Conformation.

J Am Chem Soc 2020 12 11;142(51):21450-21459. Epub 2020 Dec 11.

Departments of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.

YEATS domains are newly identified epigenetic "readers" of histone lysine acetylation (Kac) and crotonylation (Kcr). The malfunction of YEATS-Kac/Kcr interactions has been found to be involved in the pathogenesis of human diseases, such as cancer. These discoveries suggest that the YEATS domains are promising novel drug targets. We and others recently reported the development of YEATS domain inhibitors. Although these inhibitors have a general preference toward the AF9 and ENL YEATS domains, selective inhibitors targeting either YEATS domain are challenging to develop as these two proteins share a high structural similarity. In this study, we identified a proximal site outside the acyllysine-binding pocket that can differentiate AF9 YEATS from ENL YEATS. Combinatorial targeting of both the acyllysine pocket and this additional site by conformationally preorganized cyclopeptides enabled the selective inhibition of the AF9 YEATS domain. The most selective inhibitor, -, showed a 38-fold higher binding affinity toward AF9 YEATS over ENL YEATS. Further investigations indicated that - could engage with AF9 in living cells, disrupt the YEATS-dependent chromatin recruitment of AF9, and suppress the transcription of AF9 target genes.
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http://dx.doi.org/10.1021/jacs.0c10324DOI Listing
December 2020

Histone benzoylation serves as an epigenetic mark for DPF and YEATS family proteins.

Nucleic Acids Res 2021 01;49(1):114-126

MOE Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.

Histone modifications and their functional readout serve as an important mechanism for gene regulation. Lysine benzoylation (Kbz) on histones is a recently identified acylation mark associated with active transcription. However, it remains to be explored whether putative readers exist to recognize this epigenetic mark. Here, our systematic binding studies demonstrated that the DPF and YEATS, but not the Bromodomain family members, are readers for histone Kbz. Co-crystal structural analyses revealed a 'hydrophobic encapsulation' and a 'tip-sensor' mechanism for Kbz readout by DPF and YEATS, respectively. Moreover, the DPF and YEATS family members display subtle yet unique features to create somewhat flexible engagements of different acylation marks. For instance, YEATS2 but not the other YEATS proteins exhibits best preference for Kbz than lysine acetylation and crotonylation due to its wider 'tip-sensor' pocket. The levels of histone benzoylation in cultured cells or in mice are upregulated upon sodium benzoate treatment, highlighting its dynamic regulation. In summary, our work identifies the first readers for histone Kbz and reveals the molecular basis underlying Kbz recognition, thus paving the way for further functional dissections of histone benzoylation.
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http://dx.doi.org/10.1093/nar/gkaa1130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797077PMC
January 2021

Dietary Lactate Supplementation Protects against Obesity by Promoting Adipose Browning in Mice.

J Agric Food Chem 2020 Dec 7;68(50):14841-14849. Epub 2020 Dec 7.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

Yogurt has been widely used in weight-loss foods to prevent obesity, but its molecular nature remains unclear. Lactate is a major ingredient of yogurt, while its cognate cell surface receptor GPR81 is highly expressed in adipose tissues in mammals. Here we hypothesized that dietary lactate supplementation might activate GPR81 to promote adipose browning. Studying mouse models, we observed that GPR81 was substantially lowered in adipose tissue of obese mice compared with that for lean ones, whereas its expression was markedly up-regulated by a β3-adrenergic receptor (β3-AR) agonist. The deficiency of GPR81 greatly attenuated experimental adipose browning and thermogenesis. Importantly, oral administration of lactate effectively induced adipose browning, enhanced thermogenesis, improved dyslipidemia, and protected mice against high-fat-diet-induced obesity. Mechanistically, p38 mitogen-activated protein kinase might serve as a key downstream effect or of GPR81. Collectively, our findings revealed a critical role of GPR81 in adipose browning and provided a new insight into obesity management by modulating lactate-GPR81 signaling axis.
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http://dx.doi.org/10.1021/acs.jafc.0c05899DOI Listing
December 2020

Social capital, depressive symptoms, and perceived quality of care among hypertensive patients in primary care.

Health Qual Life Outcomes 2020 Dec 1;18(1):378. Epub 2020 Dec 1.

Hebei Research Institute for Human Resources and Social Security Science, Hebei, China.

Background: Depression is an important issue in the management of hypertension. However, little attention has been paid to addressing such aspects of psychological health among patients with hypertension. We aimed to estimate the prevalence of depressive symptoms among patients with hypertension in primary care settings and to identify the potential role of social capital in predicting depressive symptoms. The influence of psychological well-being on the perceived quality of hypertensive care was also examined.

Methods: In Shenzhen, China, an on-site cross-sectional study was conducted from March to September 2017. In total, 1046 respondents completed a face-to-face survey interview. We examined the associations between social capital, depressive symptoms, and perceived quality of care.

Results: The results showed that 10.7% of patients with hypertension who attended primary care facilities had depressive symptoms. Two components of social capital-social ties (9.63 vs. 10.67; OR = 1.314, 95% CI 1.165-1.483; P < .001) and trust (3.46 vs. 3.89; OR = 2.535, 95% CI 1.741-3.691; P < .001)-were protective factors for depression among patients with hypertension in primary care settings. We also found that depressive symptoms were negatively associated with perceived quality of care (30.5 vs. 32.5; β = 1.341, 95% CI 0.463-2.219; P = .003)..

Conclusions: We found inverse associations between depressive symptoms and perceived quality of care and between social capital and the occurrence of symptoms of depression. Our findings suggest that strategies addressing both hypertension and depressive symptoms should be implemented to better manage hypertension. Appropriate social interventions should be designed and implemented.
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http://dx.doi.org/10.1186/s12955-020-01630-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709396PMC
December 2020

Therapeutic effect of pulsed electromagnetic field on bone wound healing in rats.

Electromagn Biol Med 2021 Jan 29;40(1):26-32. Epub 2020 Nov 29.

Department of Surgery, Yidu Central Hospital , Weifang, China.

This study aimed to investigate the therapeutic effect of pulsed electromagnetic field (PEMF) on bone wound in rats as a potential therapy for bone fracture-related conditions. Male rats, aged 3 months, were used to construct model of bone wounding. Wound models were randomly selected to receive PEMF therapy at 1 to 10 mT intensity. Models that did not receive PEMF therapy were used as control. The serum concentrations of calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) were determined. Bone density and biomechanical properties of callus were measured using a tensile tester. Compared with control, rats subjected to PEMF therapy had similar weight gain, but significantly higher levels of serum Ca and ALP ( < .05) at 5 and 10 mT, while the serum level of P remained unchanged after PEMF therapy. The bone mineral density of callus increased after the therapy, particularly, after 5 and 10 mT therapy ( < .05). Biomechanical measurements showed that 21 days after the therapy, the maximum load, fracture load, elastic load and bending energy were significantly greater in rats receiving 5 and 10 mT PEMF therapy as compared with control ( < .05). Our experiments demonstrate that PEMF at 5 and 10 mT can significantly accelerate wound healing and enhance the repairing ability of bone tissue.
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http://dx.doi.org/10.1080/15368378.2020.1851252DOI Listing
January 2021