Publications by authors named "Lei Liu"

4,031 Publications

  • Page 1 of 1

ITPRIP promotes glioma progression by linking MYL9 to DAPK1 inhibition.

Cell Signal 2021 Jun 7:110062. Epub 2021 Jun 7.

Department of Neurosurgery, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, 1 Huanghe West Road, Huaian 223300, China. Electronic address:

Epigenetic gene silencing of the tumor suppressor death-associated protein kinase 1 (DAPK1) is implicated in the progression of malignant gliomas. However, the mechanism underlying the repression of DAPK1 in gliomas remains elusive. In this study, we identified the existence of DAPK1-inositol 1,4,5-trisphosphate receptor (IPR)-interacting protein (ITPRIP) -myosin regulatory light polypeptide 9 (MYL9) complex in malignant glioma cells. Lentivirus co-infection and coimmunoprecipitation showed that ITPRIP bound with the death domain (DD) of DAPK1 in vitro. Further, dissociating ITPRIP-DAPK1 interaction inhibited glioma tumor growth in vitro but not in vivo. Moreover, knockdown of ITPRIP or DAPK1 impaired the ternary complex formation, whereas MYL9 knockdown did not affect ITPRIP-DAPK1 association. We further found that ITPRIP recruited MYL9 to the kinase domain (KD) of DAPK1, and in turn impeded the phosphorylation of MYL9. Accordingly, interference of ITPRIP enhanced the suppressive effects of DAPK1-KD on glioma progression both in vitro and in vivo. Our results demonstrate that ITPRIP plays a crucial role in the inhibition of DAPK1 and enhancement of tumorigenic properties of malignant glioma cells.
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http://dx.doi.org/10.1016/j.cellsig.2021.110062DOI Listing
June 2021

Noninvasive Ventilation in Patients With COVID-19-Related Acute Hypoxemic Respiratory Failure: A Retrospective Cohort Study.

Front Med (Lausanne) 2021 24;8:638201. Epub 2021 May 24.

National Clinical Research Center for Infectious Disease, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.

Noninvasive ventilation (NIV) has been used to alleviate hypoxemia and dyspnea, but there is no consensus on the application of NIV in patients with coronavirus disease 2019 (COVID-19). Some staff use NIV as the rescue therapy which might lead to the adverse outcomes. This study was to identify early factors associated with intubation to help the medical staff select appropriate patients for receiving NIV treatment. Patients with laboratory-confirmed COVID-19 who were treated with NIV in emergency department or ICU of the Third People's Hospital (the only designated hospital for treating COVID-19 in Shenzhen) between January 1 and August 31, 2020, were retrospectively analyzed. Thirty-nine patients with COVID-19 treated with NIV were included; of them, 16 (41%) received endotracheal intubation and 3 (8%) died. Significant differences were observed between intubated and non-intubated patients in PaO/FiO before NIV initiation, hospitalization duration, NIV as the rescue therapy, and PaO/FiO of ≤200 mmHg after 1-2 h of NIV initiation. Notably, 1-2 h after NIV initiation, a PaO/FiO of ≤200 mmHg (odds ratio [OR], 9.35; 95% confidence interval [CI], 1.84-47.62; = 0.007) and NIV as the rescue therapy (OR, 5.43; 95% CI, 1.09-27.12; = 0.039) were the risk factors for intubation. In patients with COVID-19-related acute hypoxemic respiratory failure receiving NIV, close attention should be paid to PaO/FiO after 1-2 h of NIV initiation. Also, using NIV as rescue therapy should draw our awareness that it might delay escalation of respiratory support and lead to adverse outcomes.
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http://dx.doi.org/10.3389/fmed.2021.638201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183270PMC
May 2021

A PROTAC peptide induces durable β-catenin degradation and suppresses Wnt-dependent intestinal cancer.

Cell Discov 2020 Jun 9;6(1):35. Epub 2020 Jun 9.

The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, 100084, Beijing, China.

Aberrant activation of Wnt/β-catenin signaling has been associated with the onset and progression of many types of tumors and thus β-catenin represents one attractive intracellular target for cancer therapy. Based on the Axin-derived peptide that binds to β-catenin, two stapled peptides SAHPA1 and xStAx were reported to enhance or impair Wnt/β-catenin signaling, respectively. In this study, we designed PROTACs (proteolysis targeting chimeras) by coupling SAHPA1 or xStAx with the VHL ligand to achieve efficient β-catenin degradation. The obtained xStAx-VHLL sustained β-catenin degradation and manifested strong inhibition of Wnt signaling in cancer cells and in APC organoids. Furthermore, xStAx-VHLL could effectively restrain tumor formation in BALB/C nude mice, and diminish the existing tumors in APC mice. More importantly, xStAx-VHLL could potently inhibit the survival of colorectal cancer patient-derived organoids. These findings suggest that xStAx-VHLL exhibits the ability of cancer prevention and cure, highlighting the potential of β-catenin degrader PROTACs as a new class of promising anticancer agent.
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http://dx.doi.org/10.1038/s41421-020-0171-1DOI Listing
June 2020

New methods for quantification of Fenton's reagent addition based on aged sludge indicators to improve filterability.

J Hazard Mater 2021 May 29;418:126254. Epub 2021 May 29.

College of Resources and Environment, Hunan Agricultural University, Changsha 410128, China.

Fenton oxidation can effectively improve the dewaterability of aged sludge. Quantification of the addition of optimal reagents is central to the conditioning and dewatering of aged sludge. Improving the accuracy of quantification is significant to promote cost effectiveness. The effects of reagent addition and the mechanism governing the improved filterability of the aged sludge need to be understood uniformly. In this study, the optimal reagent additions have been determined using the response surface method (RSM) for five out of the eight aged sludges that were investigated. The physicochemical characteristics of eight aged sludges, including the extracellular polymer substance, undissolved organic matter, and suspension structure network, were investigated. Meanwhile, a comprehensive correlation analysis of critical indicators was conducted to investigate the interactions among the properties of the aged sludge. The effects of these interactions on the conditioning and filtration processes were examined, and a unified understanding of the combination of factors affecting the optimal reagent addition was obtained. The key factors were aggregate size, dewatering extent, yield stress, and organic substance content. Based on these results, a new reagent addition quantification method was developed along with an empirical model of the relationship between physicochemical properties and the economically optimal reagent addition.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126254DOI Listing
May 2021

Effects of graded levels of xylo-oligosaccharides on growth performance, serum parameters, intestinal morphology and intestinal barrier function in weaned piglets.

J Anim Sci 2021 Jun 7. Epub 2021 Jun 7.

Precision Livestock and Nutrition Unit, Gembloux Agro-Bio Tech, TERRA Teaching and Research Centre, Liège University, Passage des Déportés 2, 5030 Gembloux, Belgium.

The objective of this study was to investigate the effects of xylo-oligosaccharides (XOS) supplementation on growth performance, serum parameters, small intestinal morphology, intestinal mucosal integrity, and immune function in weaned piglets. A total of 240 weaned piglets with an average body weight (BW) of 8.82 ± 0.05 kg (28 d of age) were assigned randomly to 4 dietary treatments in a 28-d trial, including a control diet (CON), 3 diets with XOS supplementation at the concentration of 100, 500 and 1000 mg/kg (XOS100, XOS500, and XOS1000). There were 4 replicates per treatment with 15 pigs per pen. From d 1 to 14, there were no differences (P > 0.05) in average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G:F) during the different treatments. The different doses of XOS showed a quadratic effect on BW on d 28, ADG and G:F d 1-28 of piglets (P < 0.05). From d 15 to 28, ADG of pigs fed the XOS500 diet was higher (P < 0.05) than pigs fed the CON diet. During the overall period (d 1 to 28), pigs fed the XOS500 diet had a higher BW, ADG and G:F than pigs fed the CON diet (P < 0.05). In addition, compared with the CON group, the XOS500 group had significantly higher serum total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD) and catalase (CAT) levels and lower malondialdehyde (MDA) levels on d 14 and 28 (P < 0.05). The serum immunoglobulin G (IgG) concentration in the XOS500 group was also significantly higher compared with the CON group on d 14 and 28 (P <0.05). However, serum immunoglobulin A (IgA) and immunoglobulin M (IgM) were not affected by the dietary treatments. Supplementation of XOS500 to the feed significantly increased the villus height (VH) and villus height to crypt depth ratio (VH:CD) in the jejunum and ileum in comparison with the CON and XOS1000 group. Moreover, the XOS500 group significantly elevated the expression levels of Occludin and zonula occludens protein-1 (ZO-1) in the ileum compared to the CON group. The ileal interleukin (IL)-1β, IL-8 and interferon (IFN)-γ mRNA expression levels in the XOS100 and XOS500 group were markedly lower than in the CON group. In contrast, the ileal IL-10 mRNA expression levels were remarkably higher in the XOS500 than CON group. In conclusion, xylo-oligosaccharides have a beneficial effect on growth performance by improving serum antioxidant defense system, serum IgG, small intestinal structure and intestinal barrier function in weaned piglets.
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http://dx.doi.org/10.1093/jas/skab183DOI Listing
June 2021

Effect of sodium butyrate on slaughter performance, serum indexes and intestinal barrier of rabbits.

J Anim Physiol Anim Nutr (Berl) 2021 Jun 6. Epub 2021 Jun 6.

Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science, Shandong Agricultural University, Taian, China.

The purpose of this study was to investigate the effect of sodium butyrate on slaughter performance, serum indexes and the intestinal barrier in rabbits. Six hundred healthy weaned rabbits were randomly divided into three groups (5 replicates per group, 40 rabbits per replicate): control (fed a basal diet), sodium butyrate (fed a basal diet containing 0.5% sodium butyrate) and antibiotic (fed a basal diet containing 0.004% antibiotic). The trial lasted 35 days, including 7 days of pretesting and 28 days of formal testing. The results showed that dietary sodium butyrate supplementation increased the full-bore weight, the half-bore weight and the half-bore rate of rabbits. Meanwhile, the content of aspartate aminotransferase (AST) in serum was increased in rabbits fed the sodium butyrate diet. According to the intestinal barrier, after adding sodium butyrate to feed, the tight junction function of the rabbit intestine is enhanced, and the intestinal microbial composition is also improved. To sum up, after sodium butyrate was added to feed instead of antibiotics, slaughter performance was significantly enhanced, serum indexes were improved, and intestinal barrier function was also enhanced. Therefore, sodium butyrate can be added to feed as an additive and can replace antibiotics.
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http://dx.doi.org/10.1111/jpn.13571DOI Listing
June 2021

Successfully controlling the incidence of multidrug-resistant Pseudomonas aeruginosa through antibiotic stewardship and infection control programmes at a Chinese university hospital.

J Clin Pharm Ther 2021 Jun 6. Epub 2021 Jun 6.

Department of Respiratory Medicine, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

What Is Known And Objective: The purpose of this study was to investigate the effect of imposing infection control programmes (ICPs) and antimicrobial stewardship (AMS) by monitoring the antimicrobial resistance of Pseudomonas aeruginosa.

Methods: Antimicrobial susceptibility testing was performed in accordance with the Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing guidelines. ICPs and AMS were initiated at the Fourth Hospital from 2013 to 2018.

Results And Discussion: A total of 2,886 P. aeruginosa isolates were assessed. The antimicrobial resistance trends of the P. aeruginosa strains improved after the intervention measures. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) P. aeruginosa contributed to 18.5% and 3.5% of the total P. aeruginosa strains, respectively. Colistin was the most effective antibiotic against 97.6% of XDR-P. aeruginosa and 99.41% of MDR-P. aeruginosa. The consumption of alcohol-based hand gel (ABHG) increased from 0.6 L to 10.8 L per 1,000 patient-days (PD) (p = 0.005). The yearly consumption of antibiotics decreased from 45 to 37.5 defined daily doses (DDD) per 1,000 PD(p = 0.04). After 2013, the incidence rate of MDR-P. aeruginosa showed a significant decrease from 22% to 14.1% (p = 0.04), and XDR-P. aeruginosa decreased from 5.8% to 0.9%. The use of ABHG was negatively related to MDR-P. aeruginosa morbidity (r = -0.86; p = 0.021). The consumption of antibiotics was positively related to MDR-P. aeruginosa morbidity (r = 0.86; p = 0.021).

What Is New And Conclusion: Successful control of MDR-P. aeruginosa resistance was achieved by imposing comprehensive ICPs and AMS.
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http://dx.doi.org/10.1111/jcpt.13446DOI Listing
June 2021

Fe-catalyzed three-component dicarbofunctionalization of unactivated alkenes with alkyl halides and Grignard reagents.

Chem Sci 2020 Jul 24;11(31):8301-8305. Epub 2020 Jul 24.

Department of Chemistry and Biochemistry, University of Maryland College Park Maryland 20742 USA

A highly chemoselective iron-catalyzed three-component dicarbofunctionalization of unactivated olefins with alkyl halides (iodides and bromides) and sp-hybridized Grignard reagents is reported. The reaction operates under fast turnover frequency and tolerates a diverse range of sp-hybridized nucleophiles (electron-rich and electron-deficient (hetero)aryl and alkenyl Grignard reagents), alkyl halides (tertiary alkyl iodides/bromides and perfluorinated bromides), and unactivated olefins bearing diverse functional groups including tethered alkenes, ethers, protected alcohols, aldehydes, and amines to yield the desired 1,2-alkylarylated products with high regiocontrol. Further, we demonstrate that this protocol is amenable for the synthesis of new (hetero)carbocycles including tetrahydrofurans and pyrrolidines a three-component radical cascade cyclization/arylation that forges three new C-C bonds.
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http://dx.doi.org/10.1039/d0sc02127jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163237PMC
July 2020

Chemical synthesis and biological activity of peptides incorporating an ether bridge as a surrogate for a disulfide bond.

Chem Sci 2020 Jul 8;11(30):7927-7932. Epub 2020 Jul 8.

School of Food and Biological Engineering, Hefei University of Technology Hefei Anhui 230009 China

Disulfide bridges contribute to the definition and rigidity of polypeptides, but they are inherently unstable in reducing environments and in the presence of isomerases and nucleophiles. Strategies to address these deficiencies, ideally without significantly perturbing the structure of the polypeptide, would be of great interest. One possible surrogate for the disulfide bridge is a simple thioether, but these are susceptible to oxidation. We report the introduction of an ether linkage into the biologically active, disulfide-rich peptides oxytocin, tachyplesin I, and conotoxin , using an ether-containing diaminodiacid as the key building block, obtained by the stereoselective ring-opening addition reaction of an aziridine skeleton with a hydroxy group. NMR studies indicated that the derivatives with an ether surrogate bridge exhibited very small change of their three-dimensional structures. The analogs obtained using this novel substitution strategy were found to be more stable than the original peptide in oxidative and reductive conditions; without a loss of bioactivity. This strategy is therefore proposed as a practical and versatile solution to the stability problems associated with cysteine-rich peptides.
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http://dx.doi.org/10.1039/d0sc02374dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163063PMC
July 2020

Testing for mediation effect with application to human microbiome data.

Stat Biosci 2021 Jul 27;13(2):313-328. Epub 2019 Jul 27.

Division of Biostatistics, Washington University in St. Louis, St. Louis, MO 63110, USA.

Mediation analysis has been commonly used to study the effect of an exposure on an outcome through a mediator. In this paper, we are interested in exploring the mediation mechanism of microbiome, whose special features make the analysis challenging. We consider the isometric logratio transformation of the relative abundance as the mediator variable. Then, we present a de-biased Lasso estimate for the mediator of interest and derive its standard error estimator, which can be used to develop a test procedure for the interested mediation effect. Extensive simulation studies are conducted to assess the performance of our method. We apply the proposed approach to test the mediation effect of human gut microbiome between the dietary fiber intake and body mass index.
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http://dx.doi.org/10.1007/s12561-019-09253-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177450PMC
July 2021

Physicochemical stability-increasing effects of anthocyanin via a co-assembly approach with an amphiphilic peptide.

Food Chem 2021 May 13;362:130101. Epub 2021 May 13.

School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu, China; Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang, Jiangsu, China. Electronic address:

To enhance the stability of anthocyanin, an amphiphilic peptide C6 with tryptophan amino acid was used to co-assemble with anthocyanin C3G. The characterization, stabilities, and antioxidant activity of peptide-anthocyanin (C6-C3G) nanocomposites (70.82 ± 12.41 nm) were investigated. To illustrate the interaction between peptide and anthocyanin, circular dichroism spectroscopy and fluorescence quenching method were used. Here, the peptide C6 switches from random coil structure to β-sheet structure and the fluorescence of tryptophan amino acid in peptide quenched during the intermolecular interaction between them, which was further confirmed a static quenching. The nanocomposites significantly enhance the stabilities of anthocyanin to different alkaline conditions, high temperature of 80 °C, long time storage, and various concentration of Cu ion. In addition, it maintained the excellent intrinsic capacity of anthocyanin to scavenge free radicals. The approach of using an amphiphilic peptide to enhance the stabilities of anthocyanin presents a high potential to expand its application.
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http://dx.doi.org/10.1016/j.foodchem.2021.130101DOI Listing
May 2021

Outcomes of Eyes Lost to Follow-Up in Patients with Central Retinal Vein Occlusion Who are Receiving Anti-Vascular Endothelial Growth Factor Treatment.

Ther Clin Risk Manag 2021 26;17:489-496. Epub 2021 May 26.

Department of Ophthalmology, The First Hospital of China Medical University, Shenyang, People's Republic of China.

Background: To evaluate the anatomic and functional outcomes in eyes of patients with macular edema (ME) caused by central retinal vein occlusion (CRVO) who were lost to follow-up (LTFU) for more than 6 months following treatment with anti-vascular endothelial growth factor (VEGF) therapy and to determine the predictive factors of visual prognosis in these patients.

Methods: This study was conducted as a retrospective, case series investigation. Patients whose eyes were receiving intravitreal anti-VEGF treatment for CRVO-ME, with the next follow-up visit occurring more than 6 months following treatment were identified. Baseline disease characteristics (at the last visit before being LTFU), cause and duration of treatment interruption, and the resulting disease progression, complications, and outcomes were assessed. Baseline characteristics predictive of visual outcome were also analyzed.

Results: This study included a total of 17 eyes of 17 patients. The mean duration of being LTFU was 7.8 ± 2.1 months. On the return visit after being LTFU, 7 of 17 eyes (41.2%) developed neovascular complications. Despite treatment, 12 eyes (70.1%) lost ≥3 best-corrected visual acuity (BCVA) lines, with 2 eyes (11.8%) developing a final BCVA of hand motion or more severe. At the final visit, the mean logarithm of minimal angle of resolution (logMAR) BCVA deteriorated significantly compared to before being LTFU (P < 0.001). The increasing duration of being LTFU is associated with a deterioration of visual acuity prognosis.

Conclusion: In CRVO-ME patients who are receiving anti-VEGF therapy, unintentional treatment interruptions can cause visually disastrous consequences, including irreversible blindness. Patients who were LTFU for a long period should be strongly warned about their poor visual prognosis.
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http://dx.doi.org/10.2147/TCRM.S303248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165207PMC
May 2021

Down-Regulation of Gene Expression Alters Lysophospholipid Composition in the Endosperm of Rice Grain and Influences Starch Properties.

Foods 2021 May 23;10(6). Epub 2021 May 23.

Commonwealth Scientific and Industrial Research Organisation, Agriculture & Food, Acton, ACT 2601, Australia.

Small quantities of lipids accumulate in the white rice grains. These are grouped into non-starch lipid and starch lipid fractions that affect starch properties through association with starch. Lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) are two major lipid classes in the two fractions. Using high-oleic rice grains, we investigated the fatty-acid composition in flour and starch by LC-MS and evaluated its impact on starch properties. In the wild-type grain, nearly 50% of fatty acids in LPC and LPE were palmitic acid (C16:0), over 20% linoleic acid (C18:2) and less than 10% oleic acid (C18:1). In the high-oleic rice grain, C18:1 increased at the expense of C18:2 and C16:0. The compositional changes in starch lipids suggest that LPC and LPE are transported to an amyloplast with an origin from endoplasmic reticulum-derived PC and PE during endosperm development. The high-dissociation temperature of the amylose-lipid complex (ALC) and restricted starch swelling power in the high-oleic rice starch indicates that the stability of the ALC involving C18:1 is higher than that of C18:2 and C16:0. This study provides insight into the lipid deposition and starch properties of rice grains with optimized fatty-acid composition.
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http://dx.doi.org/10.3390/foods10061169DOI Listing
May 2021

Next Generation Cereal Crop Yield Enhancement: From Knowledge of Inflorescence Development to Practical Engineering by Genome Editing.

Int J Mol Sci 2021 May 13;22(10). Epub 2021 May 13.

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

Artificial domestication and improvement of the majority of crops began approximately 10,000 years ago, in different parts of the world, to achieve high productivity, good quality, and widespread adaptability. It was initiated from a phenotype-based selection by local farmers and developed to current biotechnology-based breeding to feed over 7 billion people. For most cereal crops, yield relates to grain production, which could be enhanced by increasing grain number and weight. Grain number is typically determined during inflorescence development. Many mutants and genes for inflorescence development have already been characterized in cereal crops. Therefore, optimization of such genes could fine-tune yield-related traits, such as grain number. With the rapidly advancing genome-editing technologies and understanding of yield-related traits, knowledge-driven breeding by design is becoming a reality. This review introduces knowledge about inflorescence yield-related traits in cereal crops, focusing on rice, maize, and wheat. Next, emerging genome-editing technologies and recent studies that apply this technology to engineer crop yield improvement by targeting inflorescence development are reviewed. These approaches promise to usher in a new era of breeding practice.
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http://dx.doi.org/10.3390/ijms22105167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153303PMC
May 2021

Membrane Profiling by Free Flow Electrophoresis and SWATH-MS to Characterize Subcellular Compartment Proteomes in .

Int J Mol Sci 2021 May 9;22(9). Epub 2021 May 9.

Southern Cross Plant Science, Faculty of Science and Engineering, Southern Cross University, Lismore, NSW 2480, Australia.

The study of subcellular membrane structure and function facilitates investigations into how biological processes are divided within the cell. However, work in this area has been hampered by the limited techniques available to fractionate the different membranes. Free Flow Electrophoresis (FFE) allows for the fractionation of membranes based on their different surface charges, a property made up primarily of their varied lipid and protein compositions. In this study, high-resolution plant membrane fractionation by FFE, combined with mass spectrometry-based proteomics, allowed the simultaneous profiling of multiple cellular membranes from the leaf tissue of the plant . Comparisons of the fractionated membranes' protein profile to that of known markers for specific cellular compartments sheds light on the functions of proteins, as well as provides new evidence for multiple subcellular localization of several proteins, including those involved in lipid metabolism.
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http://dx.doi.org/10.3390/ijms22095020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126025PMC
May 2021

Study on the ecological risk of heavy metals during oily sludge incineration with CaO additive.

J Environ Sci Health A Tox Hazard Subst Environ Eng 2021 Jun 1:1-7. Epub 2021 Jun 1.

College of New Energy, China University of Petroleum (East Chian), Qingdao, China.

In order to explore the effect of CaO on the ecological risk of chromium (Cr), copper (Cu) and zinc (Zn) in Oily sludge (OS), the incineration experiments of OS with and without calcium oxide (CaO) additive were carried out respectively in a horizontal tube furnace at the temperature ranging from 800 °C to 1000 °C. Furthermore, the ecological risk based on Risk Assessment Code (RAC) of Cr, Cu and Zn in OS, bottom ash from OS incineration (OSA) and bottom ash from OS incineration in the presence of CaO additive (OSA-CaO) were investigated in this work. The results showed that most of the Cr and Cu in OS remained in bottom ash, while Zn volatilized with the flue gas. At the same time, the RAC of Cr, Cu and Zn in OS decreased significantly after incineration. Compared with OSA, CaO obviously promoted the stabilization of Cr and Cu in OSA-CaO, but had little effect on the behavior of Zn. Moreover, CaO also reduced the RAC of Cu and Zn in samples, and reduced its harm to ecosystem. This study supplied essential data and theoretical support for the industrial treatment of OS, and was of great help to the harmless treatment of OS.
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http://dx.doi.org/10.1080/10934529.2021.1927598DOI Listing
June 2021

Comparison of antibiotic-associated diarrhea caused by cefoperazone/sulbactam or piperacillin/tazobactam in neurosurgery patients.

J Int Med Res 2021 May;49(5):3000605211019661

Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China.

Objective: To compare the occurrence and prognosis of antibiotic-associated diarrhea (AAD) between patients treated with cefoperazone/sulbactam and piperacillin/tazobactam in the neurosurgery department.

Methods: This study retrospectively analyzed patients who received cefoperazone/sulbactam or piperacillin/tazobactam to prevent or treat hospital-acquired infections in the Department of Neurosurgery of The First Medical Center of Chinese PLA General Hospital between October 2019 and October 2020. For patients with AAD, clinical data, antibiotic usage, the incidence of diarrhea, treatment, and prognosis were collected and analyzed.

Results: In total, 356 patients were enrolled, and 65 (18.6%) experienced AAD, 38 patients in the cefoperazone/sulbactam group and 27 patients in the piperacillin/tazobactam group. The AAD rate did not differ between the treatment arms. Conversely, the dosage, intensity, and duration of antibiotic therapy differed between the groups, whereas no differences were noted in the time to the appearance of diarrhea and prognosis. According to regression analysis, the incidence of AAD did not differ between the groups (odds ratio [OR] = 0.85, 95% confidence interval [CI] = 0.46-1.48).

Conclusion: Cefoperazone/sulbactam or piperacillin/tazobactam can lead to a similar incidence rate of AAD. The combined application of antibiotics and empiric therapy often occurs. The rational use of antibiotics should be improved.
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http://dx.doi.org/10.1177/03000605211019661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170296PMC
May 2021

Epidemiological analysis of cystic echinococcosis and alveolar echinococcosis in an extremely high prevalence region: Population-based survey and host animal monitoring in Shiqu County, China.

Acta Trop 2021 May 25;221:105982. Epub 2021 May 25.

Sichuan Center for Animal Disease Control and Prevention, Chengdu, China.

Echinococcosis is the most common parasitic disease in the Tibetan Plateau, placing a large disease burden on the local population. Shiqu County, located in western Sichuan Tibetan region, had a particularly high prevalence rate of cystic echinococcosis (CE) and alveolar echinococcosis (AE) in previous surveys. From 2015 to 2018, a population-based field survey was conducted to explore the epidemic situation. Epidemiological features were examined through demographic analysis and mapping. In addition, the infection prevalence of Echinococcus in dogs was also investigated and mapped by spatial autoregression. A total of 84,768 people were screened by abdominal ultrasound inspection, and 2,341 CE and 3,930 AE cases were detected, with a corresponding prevalence of 2.76% and 4.64%, respectively. This made Shiqu County one of the most severe echinococcosis endemic regions in the world, especially with regard to AE. The cases were not evenly distributed among towns: particularly, the AE rates in the northwest towns were very high and closely related to the infection rate of neighboring host animals. Simultaneously, a comprehensive prevention project including patient treatment and host management was conducted and achieved preliminary success in source control. According to feces monitoring findings, the infection rate of dogs declined from 26.38% in early 2016 to 3.71% in 2018. Combined with host animal distribution data at the town level, the predicted risk ranks were categorized by risk index and mapped to guide further control operations.
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http://dx.doi.org/10.1016/j.actatropica.2021.105982DOI Listing
May 2021

Metabolomics study of fibroblasts damaged by UVB and BaP.

Sci Rep 2021 May 27;11(1):11176. Epub 2021 May 27.

Beijing Key Laboratory of Plant Resources Research and Development, College of Chemistry and Meterials Engineering, Beijing Technology and Business University, Beijing, 100048, China.

We have recently shown that both UVB and BaP can induce the production of ROS, apoptosis and even cancer. However, the differences in the metabolic profiles of skin damaged by UVB, BaP or UVB combined with BaP have not been studied. Therefore, we examined the metabolic changes in the human foreskin fibroblast injured by UVB or BaP or the combination of the two, using ultra performance liquid chromatography (UPLC) coupled with quadrupole time-of-flight mass spectrometry (qTOF-MS). 24 metabolites were altered in the UVB damage group, 25 in the BaP damage group, and 33 in the UVB combined with BaP group. These alterations indicated that the metabolic mechanisms of HFF-1 cells treated with UVB or BaP are related to multiple main metabolites including glycerophosphocholine (PC), lactosylceramide (LacCer), guanidinosuccinic acid (GSA), glutathione(GSH), and lysophosphatidylcholine (LysoPC) and the main mechanisms involved glycerophospholipid and glutathione metabolism. Thus, our report provided useful insight into the underlying mechanisms of UVB and BaP damage to skin cells.
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http://dx.doi.org/10.1038/s41598-021-90186-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160258PMC
May 2021

Iron deficiency-induced transcription factors bHLH38/100/101 negatively modulate flowering time in Arabidopsis thaliana.

Plant Sci 2021 Jul 2;308:110929. Epub 2021 May 2.

State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming 650091, China. Electronic address:

The mechanisms regulating flowering have been extensively studied and the roles of many environmental signals in this process have been reported. However, little is known on the relationship between iron deficiency and flowering regulation, although the response mechanism to iron deficiency has been studied for decades. In this study, we observed that the flowering time of wild-type Arabidopsis thaliana was significantly repressed by iron deficiency under long days. Phenotype analysis showed that iron deficiency delayed flowering of Arabidopsis through the iron deficiency-induced transcription factors bHLH38, bHLH100, and bHLH101 (bHLH38/100/101), which redundantly regulated flowering time and expression of FLOWERING LOCUS T (FT) specifically under long days. Genetic analysis indicated that disruption of FT expression suppressed the early-flowering phenotype of bhlh38/100/101 triple-mutant plants, indicating that bHLH38/100/101 are dependent on functional FT. Furthermore, bHLH38/100/101 interacted with CONSTANS (CO), thereby interfering with the transcriptional activation of CO to regulate FT expression. Therefore, the results indicated that iron deficiency affects flowering of Arabidopsis under long days through bHLH38/100/101-CO-FT signaling.
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http://dx.doi.org/10.1016/j.plantsci.2021.110929DOI Listing
July 2021

Quasispecies of SARS-CoV-2 revealed by single nucleotide polymorphisms (SNPs) analysis.

Virulence 2021 12;12(1):1209-1226

Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong Province, China.

New SARS-CoV-2 mutants have been continuously indentified with enhanced transmission ever since its outbreak in early 2020. As an RNA virus, SARS-CoV-2 has a high mutation rate due to the low fidelity of RNA polymerase. To study the single nucleotide polymorphisms (SNPs) dynamics of SARS-CoV-2, 158 SNPs with high confidence were identified by deep meta-transcriptomic sequencing, and the most common SNP type was C > T. Analyses of intra-host population diversity revealed that intra-host quasispecies' composition varies with time during the early onset of symptoms, which implicates viral evolution during infection. Network analysis of co-occurring SNPs revealed the most abundant non-synonymous SNP 22,638 in the S glycoprotein RBD region and 28,144 in the ORF8 region. Furthermore, SARS-CoV-2 variations differ in an individual's respiratory tissue (nose, throat, BALF, or sputum), suggesting independent compartmentalization of SARS-CoV-2 populations in patients. The positive selection analysis of the SARS-CoV-2 genome uncovered the positive selected amino acid G251V on ORF3a. lternative llele requency pectrum (AAFS) of all variants revealed that ORF8 could bear alternate alleles with high frequency. Overall, the results show the quasispecies' profile of SARS-CoV-2 in the respiratory tract in the first two months after the outbreak.
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http://dx.doi.org/10.1080/21505594.2021.1911477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158041PMC
December 2021

Treatment of lactational breast abscesses with cavity diameter larger than 5 cm via combined ultrasonography-guided percutaneous catheter placement and hydrostatic pressure irrigation.

J Obstet Gynaecol 2021 May 25:1-4. Epub 2021 May 25.

Department of Ultrasonography, Ordos Center Hospital, Ordos, China.

This study reports on our experience of treating lactational breast abscesses larger than 5 cm via ultrasonography (US)-guided percutaneous catheter placement and hydrostatic pressure irrigation. Twelve cases of puerperal single breast abscesses larger than 5 cm were collected. These patients were treated with US-guided percutaneous catheter placement and hydrostatic pressure irrigation combined with oral antibiotics. All 12 patients using US-guided treatment were completely successful without conversion to open surgical drainage. The range of recovery time was 5-16 days, and no major complications occurred. The patients were satisfied with the appearance of the scar, and there were no reports of recurrence during the follow-up period.Overall, US-guided percutaneous catheter placement and hydrostatic pressure irrigation are successful strategies for the treatment of lactational breast abscesses larger than 5 cm. These methods not only reduce the treatment time and improve the patients' clinical course but also provide cosmetic effects.IMPACT STATEMENT The current consensus on breast abscess treatment is that lesions <3 cm can be effectively treated by aspiration alone, lesions >3 cm require catheter drainage, lesions <5 cm have proven to be safe and effectively treated by US-guided ultrasound therapy, and lesions >5 cm, whether multi-loculated or longstanding, require surgical incision and drainage. We tried to use this method to increase the cure rate of US-guided minimally invasive treatment for large abscesses. The results showed that all patients were cured successfully, requiring no further surgical intervention. Moreover, no complications occurred, and no patients developed sequelae. During the three-month follow-up period, there was no evidence of recurrence in any case. Questions remain regarding the treatment's generalisability, potentially lengthy hospitalisation, and technical limitations of the existing instrumentation. Long-term follow up and larger sample size Randomised clinical trials studies are still needed to rigorously and scientifically ensure the method's benefits over conventional open surgery in the future.
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http://dx.doi.org/10.1080/01443615.2021.1907558DOI Listing
May 2021

Molecular mechanism underlying modulation of TRPV1 heat activation by polyols.

J Biol Chem 2021 May 19:100806. Epub 2021 May 19.

Department of Biophysics, and Kidney Disease Center of the First Affiliated Hospital, Zhejiang University School of Medicine, 310058 Hangzhou, Zhejiang Province, China. Electronic address:

Sensing noxiously high temperatures is crucial for living organisms to avoid heat-induced injury. The TRPV1 channel has long been known as a sensor for noxious heat. However, the mechanism of how this channel is activated by heat remains elusive. Here we found that a series of polyols including sucrose, sorbitol, and hyaluronan significantly elevate the heat activation threshold temperature of TRPV1. The modulatory effects of these polyols were only observed when they were perfused extracellularly. Interestingly, mutation of residues E601 and E649 in the outer pore region of TRPV1 largely abolished the effects of these polyols. We further observed that intraplantar injection of polyols into the hind paws of rats reduced their heat-induced pain response. Our observations not only suggest that the extracellular regions of TRPV1 are critical for the modulation of heat activation by polyols, but also indicate a potential role of polyols in reducing heat-induced pain sensation.
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http://dx.doi.org/10.1016/j.jbc.2021.100806DOI Listing
May 2021

Chemical synthesis of activity-based E2-ubiquitin probes for the structural analysis of E3 ligase-catalyzed transthiolation.

Angew Chem Int Ed Engl 2021 May 22. Epub 2021 May 22.

Hefei University of Technology, Chemistry, CHINA.

Activity-based E2 conjugating enzyme (E2)-ubiquitin (Ub) probes have recently emerged as effective tools for studying the molecular mechanism of E3 ligase (E3)-catalyzed ubiquitination. However, the preparation of existing activity-based E2-Ub probes depends on recombination technology and bioconjugation chemistry, limiting their structural diversity. Herein we describe an expedient total chemical synthesis of an E2 enzyme variant through a hydrazide-based native chemical ligation, which enabled the construction of a structurally new activity-based E2-Ub probe to covalently capture the catalytic site of Cys-dependent E3s. Chemical cross-linking coupled with mass spectrometry (CXMS) demonstrated the utility of this new probe in structural analysis of the intermediates formed during Nedd4 and Parkin-mediated transthiolation. This study exemplifies the utility of chemical protein synthesis for the development of protein probes for biological studies.
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http://dx.doi.org/10.1002/anie.202105870DOI Listing
May 2021

Metabolic profiles of in biofilm and planktonic states and investigation of its intestinal modulation and immunoregulation in dogs.

Food Funct 2021 May 20. Epub 2021 May 20.

School of food science and bioengineering, Xihua University, Hongguang Street, Pidu District, Chengdu, 610039, China.

The use of probiotics has recently become a considerably promising research area. The most advanced fourth-generation probiotics involve beneficial bacteria enclosed in biofilms. However, differences in the effects of probiotics in biofilm and those in planktonic states are, as yet, unclear. In this study, it was ascertained that the biofilm mode of Lactobacillus paraplantarum L-ZS9 had a comparatively higher density and stronger resistance. Untargeted metabolomics analysis suggested a significant distinction between planktonic and biofilm cells, with amino acids and carbohydrate metabolism both more active in the biofilm mode. Furthermore, the in vivo experiment showed that the biofilm strain displayed better immunomodulation activity, which could increase the relative abundance of Lactobacillus in the intestinal microbiota of dogs. The relative abundance of intestinal microbiota participating in carbohydrate metabolism was higher in the biofilm probiotic-treated dogs. Correlation analysis between L-ZS9-producing metabolites, dog intestinal microbiome diversity and dog blood immune indexes (sIgA or IgG) revealed the interaction between these three components, which might explain the mechanisms by which biofilm L-ZS9 regulated the intestinal microbiome and immunity activity of the host, through the production of various metabolites. Findings of this study will, thus, enhance understanding of the beneficial effects of biofilm probiotics, as well as provide references for further investigation.
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http://dx.doi.org/10.1039/d1fo00905bDOI Listing
May 2021

The impact of neutrophil extracellular traps on deep venous thrombosis in patients with traumatic fractures.

Clin Chim Acta 2021 Aug 18;519:231-238. Epub 2021 May 18.

Department of Laboratory Medicine, Beijing Jishuitan Hospital, Peking University Fourth School of Clinical Medicine, Beijing, China; Department of Laboratory Medicine, Beijing Jishuitan Hospital, Beijing, China. Electronic address:

Background: Deep venous thrombosis (DVT) is the most common complication in patients with traumatic fractures. The neutrophil extracellular traps (NETs) can promote thrombus formation. In this prospective study, we investigated the role of NETs in thrombosis in patients with traumatic fractures to evaluate whether the biomarkers of NETs can be used to help predict the risk of thrombosis.

Methods: Traumatic fracture patients were enrolled in this prospective observational cohort study. Healthy controls (Control); patients with lower extremity fractures who neither present with nor develop DVT (Trauma non-DVT); patients with lower extremity fractures who do not present with DVT but do develop DVT (Trauma DVT); and patients with lower extremity fractures who present with DVT (DVT) were included. NETs biomarker levels of Citrullinated Histone H3 (H3Cit), cell-free DNA (cfDNA) and nucleosomes in the plasma were determined. The D-dimer and fibrin(-ogen) degradation products (FDP) level in plasma was measured. Statistical analysis of the test results was performed to assess changes in NETs biomarker levels during thrombosis in patients with traumatic fractures.

Results: The H3Cit levels in the DVT group were significantly greater than in the Trauma non-DVT group and Trauma DVT group (1.88(1.11, 3.35) ng/ml Vs 0.38(0.10, 1.17) ng/ml, P ≤ 0.05). The level of cfDNA was significantly greater in patients with traumatic fractures and was higher after thrombosis than before. The levels of D-dimer in the DVT, Trauma DVT, and Trauma non-DVT groups were significantly greater than in the Control group (5.11(3.97, 8.11) mg/l; 6.12(2.59, 18.49) mg/l; 2.99(0.99, 9.02) mg/l Vs 0.18(0.08,0.24) mg/l, P < 0.05). The distribution of FDP levels in each group was similar to that of D-dimer. Data are presented as medians (25th percentile, 75th percentile).

Conclusions: NETs released by neutrophils are involved in the formation of DVTs in patients with traumatic fractures. H3Cit and cfDNA can assist the diagnosis of DVT in patients with traumatic fractures.
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http://dx.doi.org/10.1016/j.cca.2021.04.021DOI Listing
August 2021

Activation of TRPM8 channel inhibits contraction of the isolated human ureter.

Neurourol Urodyn 2021 May 20. Epub 2021 May 20.

Department of Urology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Shandong University, Jinan, Shandong, China.

Aims: The transient receptor potential melastin-8 (TRPM8) channel is a "cooling" receptor expressed in primary sensory neurons and can be activated by compounds like menthol or icilin. TRPM8 is involved in the regulation of urinary bladder sensory function and contraction, but the role of TRPM8 in the ureter, particularly in the human ureter, is poorly understood. The aim of this study is to examine the effects of TRPM8 activation on human ureter contraction.

Methods: Human ureters were acquired from 20 patients undergoing radical nephrectomy. Contractions of ureter strips were recorded by an isometric transducer in the organ bath. Ureteral TRPM8 expression in the human ureter was examined by immunofluorescence and western blot.

Results: The two TRPM8 agonists menthol and icilin both reduced the frequency of spontaneous, electrical field stimulation, or neurokinin A-evoked ureteral contractions in a dose-dependent manner. The inhibitory effects were decreased by 10-fold in mucosa-denuded strips. The inhibitory effects of TRPM8 agonists were mimicked by calcitonin gene-related peptide (CGRP), and were blocked by KRP2579 (a TRPM8 antagonist), tetrodotoxin (a sodium channel blocker), olcegepant (BIBN, a CGRP receptor antagonist), SQ22536 (an adenylate cyclase antagonist), or H89 (a nonspecific cAMP-dependent protein kinase A inhibitor). TRPM8 was coexpressed with CGRP on the nerves located in the suburothelial and intermuscular regions and was not expressed in the urothelium.

Conclusions: The TRPM8 channel expressed on sensory nerve terminals of the human ureter is involved in the inhibitory sensory neurotransmission and modulate ureter contraction via the CGRP-adenylyl cyclase-protein kinase A pathway. TRPM8 may be involved in stone-induced changes in ureter contraction or pain.
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http://dx.doi.org/10.1002/nau.24689DOI Listing
May 2021

Persistent SARS-CoV-2-positive over 4 months in a COVID-19 patient with CHB.

Open Med (Wars) 2021 11;16(1):749-753. Epub 2021 May 11.

Department of Infectious Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People's Republic of China.

In recent months, the novel coronavirus disease 2019 (COVID-19) pandemic has become a major public health crisis with takeover more than 1 million lives worldwide. The long-lasting existence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not yet been reported. Herein, we report a case of SARS-CoV-2 infection with intermittent viral polymerase chain reaction (PCR)-positive for >4 months after clinical rehabilitation. A 35-year-old male was diagnosed with COVID-19 pneumonia with fever but without other specific symptoms. The treatment with lopinavir-ritonavir, oxygen inhalation, and other symptomatic supportive treatment facilitated recovery, and the patient was discharged. However, his viral PCR test was continually positive in oropharyngeal swabs for >4 months after that. At the end of June 2020, he was still under quarantine and observation. The contribution of current antivirus therapy might be limited. The prognosis of COVID-19 patients might be irrelevant to the virus status. Thus, further investigation to evaluate the contagiousness of convalescent patients and the mechanism underlying the persistent existence of SARS-CoV-2 after recovery is essential. A new strategy of disease control, especially extending the follow-up period for recovered COVID-19 patients, is necessary to adapt to the current situation of pandemic.
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http://dx.doi.org/10.1515/med-2021-0283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114950PMC
May 2021

Influential Periods in Longitudinal Clinical Cardiovascular Health Scores.

Am J Epidemiol 2021 May 20. Epub 2021 May 20.

Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

The prevalence of ideal cardiovascular health (CVH) among adults in the United States is low, and decreases with age. Our objective was to identify specific age windows when the loss of CVH accelerates, to ascertain preventive opportunities for intervention. This study pools data from five longitudinal cohorts (Project Heartbeat!, Cardiovascular Risk in Young Finns Study, The Bogalusa Heart Study, Coronary Artery Risk Development in Young Adults (CARDIA), Special Turku Coronary Risk Factor Intervention Project (STRIP)) from the United States and Finland from 1973 to 2012. Individuals with clinical CVH factors (body mass index, blood pressure, cholesterol, blood glucose) measured between ages 8 to 55 were included. These factors were categorized and summed into a clinical CVH score ranging from 0 (worst) to 8 (best). Adjusted segmented linear mixed models were used to estimate the change in CVH over time. Among the 18,343 participants, 9461(52%) were female and 12,346(67%) White. The baseline mean (SD) clinical CVH score was 6.9(1.2) at an average age of 17.6(8.1). Two inflection points were estimated, at 16.9 years (95% CI: 16.4, 17.4) and at 37.2 years (95% CI: 32.4, 41.9). Late adolescence and early middle age appear to be influential periods at which the loss of CVH accelerates.
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http://dx.doi.org/10.1093/aje/kwab149DOI Listing
May 2021

KDM6A-ARHGDIB axis blocks metastasis of bladder cancer by inhibiting Rac1.

Mol Cancer 2021 May 18;20(1):77. Epub 2021 May 18.

Key Laboratory for Experimental Teratology of Ministry of Education, Department of Medical Genetics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China.

Background: KDM6A, a histone demethylase, is frequently mutated in bladder cancer (BCa). However, the role and detailed molecular mechanism of KDM6A involved in bladder cancer progression remains unknown.

Methods: Tissue specimens were used to determine the expression levels and prognostic values of KDM6A and ARHGDIB. The MTT, colony formation, wound healing and Transwell migration and invasion assays were employed to detect the BCa cell proliferation, migration and invasion, respectively. Chemotaxis of macrophages was used to evaluate the ability of KDM6A to recruit macrophages. A subcutaneous tumour model and tail vein tumour injection in nude mice were used to assess the role of KDM6A in vivo. RNA sequencing, qPCR, Western blot, ChIP and phalloidin staining assay were performed to investigate the molecular functions of KDM6A. Dual-luciferase reporter assay was used to determine the effects of KDM6A and FOXA1 on the promoters of the ARHGDIB and KDM6A.

Results: We showed that the KDM6A inhibited the motility and invasiveness of the BCa cells. Mechanistically, KDM6A promotes the transcription of ARHGDIB by demethylating histone H3 lysine di/trimethylation (H3K27me2/3) and consequently leads to inhibition of Rac1. EZH2, which catalyses the methylation of H3K27, functions to silence ARHGDIB expression, and an EZH2 inhibitor can neutralize the metastatic effect caused by KDM6A deficiency. Furthermore, we demonstrated that FOXA1 directly binds to the KDM6A promoter and thus transactivates KDM6A, leading to diminished metastatic potential.

Conclusion: Our findings establish the critical role of the FOXA1-KDM6A-ARHGDIB axis in restraining the malignancy of BCa and identify KDM6A and EZH2 as potential therapeutic targets in the management of BCa.
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http://dx.doi.org/10.1186/s12943-021-01369-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130406PMC
May 2021