Publications by authors named "Zhijie Liu"

234 Publications

LARP7 ameliorates cellular senescence and aging by allosterically enhancing SIRT1 deacetylase activity.

Cell Rep 2021 Nov;37(8):110038

Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Department of Pediatric Cardiology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China. Electronic address:

Cellular senescence is associated with pleiotropic physiopathological processes, including aging and age-related diseases. The persistent DNA damage is a major stress leading to senescence, but the underlying molecular link remains elusive. Here, we identify La Ribonucleoprotein 7 (LARP7), a 7SK RNA binding protein, as an aging antagonist. DNA damage-mediated Ataxia Telangiectasia Mutated (ATM) activation triggers the extracellular shuttling and downregulation of LARP7, which dampens SIRT1 deacetylase activity, enhances p53 and NF-κB (p65) transcriptional activity by augmenting their acetylation, and thereby accelerates cellular senescence. Deletion of LARP7 leads to senescent cell accumulation and premature aging in rodent model. Furthermore, we show this ATM-LARP7-SIRT1-p53/p65 senescence axis is active in vascular senescence and atherogenesis, and preventing its activation substantially alleviates senescence and atherogenesis. Together, this study identifies LARP7 as a gatekeeper of senescence, and the altered ATM-LARP7-SIRT1-p53/p65 pathway plays an important role in DNA damage response (DDR)-mediated cellular senescence and atherosclerosis.
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http://dx.doi.org/10.1016/j.celrep.2021.110038DOI Listing
November 2021

Upcycle hazard against other hazard: Toxic fluorides from plasma fluoropolymer etching turn novel microbial disinfectants.

J Hazard Mater 2021 Nov 2:127658. Epub 2021 Nov 2.

State Key Laboratory of Electrical Insulation and Power Equipment, Center for Plasma Biomedicine, Xi'an Jiaotong University, Xi'an 710049, PR China.

The release of toxic fluoride byproducts is a seemingly unavoidable artifact of surface engineering, causing severe environmental and human health problems. Here we propose and implement a new "upcycle hazard against other hazard" concept in the case study of cold atmospheric plasma surface modification of fluoropolymers such as polytetrafluorethylene (PTFE). Capitalizing on the excellent controllability, precision and energy efficiency of the plasma surface processing, complemented with the recently discovered ability of plasmas to activate water to produce a potent electrochemical disinfectant, referred to as the plasma-activated water (PAW), we demonstrate a radically new solution to capture the hazardous gaseous fluorides into the PAW and use the as-fluorinated PAW (F-PAW) as a very effective antimicrobial disinfectant. A customized surface discharge reactor is developed to evaluate the effects of fluorides released from the plasma etching of PTFE on the chemistries in gas-phase plasmas and F-PAW, as well as the antibacterial effect of F-PAW. The results show that gaseous fluorides, including COF, CFCOF, and SiF are produced in gas-phase plasmas, and the dissolution of thus-generated fluorides into PAW has a strong effect on inactivating catalase and destroying the oxidation resistance of bacterial cells. As a result, the antibacterial effect of PAW-fluorides against the methicillin-resistant Staphylococcus aureus (MRSA) is enhanced by > 5 log reductions, suggesting that otherwise hazardous fluorides from the plasma processing of PTFE can be used to enhance the microbial disinfection efficiency of PAW. The demonstrated approach opens new avenues for sustainable hazard valorization exemplified by converting toxic fluoride-etching products into potent antimicrobial and potentially anti-viral disinfectants.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127658DOI Listing
November 2021

Using pulmonary artery acceleration time to evaluate pulmonary hemodynamic changes on preterm infants with respiratory distress syndrome.

Transl Pediatr 2021 Sep;10(9):2287-2297

Department of Pediatric Cardiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Pulmonary artery acceleration time (PAAT) is a reliable and non-invasive method for assessing pulmonary hemodynamics. To date, few studies have used PAAT to assess preterm infants, especially those with respiratory distress syndrome (RDS). This study aimed to assess changes in PAAT among preterm infants with RDS undergoing pulmonary surfactant (PS) therapy or not, and determine its potential effects on the pulmonary vascular disease (PVD) outcomes of preterm infants with RDS in the late postnatal period.

Methods: The risk of RDS was reviewed in 62 preterm infants with a gestational age of 26-31 weeks. The infants receiving PS therapy were allocated to the PS group, and the others were allocated to the control group. PAAT, right ventricular ejection time (RVET), and other ultrasonic parameters at 3 different time points after birth were studied and compared.

Results: Infants in the PS group had a significantly lower PAAT (52.7±5.9 59.6±8.7; P=0.001) and PAAT/RVET (0.30±0.03 0.33±0.03; P=0.001) than those in the control group at 36 weeks postmenstrual age (PMA). No significant increases in PAAT/RVET were detected at 3 different times for the PS group (P=0.117), but both PAAT and PAAT/RVET increased significantly with time after birth in the control group (P<0.001).

Conclusions: Preterm infants with RDS might still have PVD in the late postnatal period and thus require long-term follow-up observation. PAAT appears to be a reliable non-invasive screening measure for evaluating pulmonary hemodynamics in preterm infants with RDS and late PVD.
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http://dx.doi.org/10.21037/tp-21-341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506067PMC
September 2021

Vibration Suppression of a High-Rise Building With Adaptive Iterative Learning Control.

IEEE Trans Neural Netw Learn Syst 2021 Nov 1;PP. Epub 2021 Nov 1.

This article considers the design of an adaptive iterative learning controller for high-rise buildings with active mass dampers (AMDs). High-rise buildings in this article are seen as distributed parameter systems, in which the characteristics of every point in buildings should be considered. Two partial differential equations (PDEs) and several ordinary differential equations are used to describe the model of buildings. To achieve the control target that is to suppress the vibration induced by high winds, an adaptive iterative learning controller is proposed for the flexible building system with boundary disturbance. The convergency of the adaptive iterative learning control (AILC) approach is proven by serious theory analysis. In simulations and experiments, this article uses both the analysis of figures and quantitative analysis (root-mean-square values) to illustrate the efficiency of the AILC scheme.
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http://dx.doi.org/10.1109/TNNLS.2021.3120838DOI Listing
November 2021

CircSETD3 (Hsa_circ_0000567) Suppresses Hepatoblastoma Pathogenesis Targeting the miR-423-3p/Bcl-2-Interacting Mediator of Cell Death Axis.

Front Genet 2021 29;12:724197. Epub 2021 Sep 29.

Department of Neonatal Surgery, Ulumuqi Children's Hospital, Ulumuqi, China.

Up until now, the role of circSETD3 (Has_circ_0000567) in regulating cancer development has been reported in several tumors, but the role and regulatory mechanism of circSETD3 in hepatoblastoma (HB) remain unclear. The qPCR and western blotting were used to determine the mRNA and protein levels in the present study. Stability of circular RNA was detected by RNA digested experiments. The gain-of-function and rescue experiments were used to explore the function and mechanism of circSETD3 in HB. Cell counting kit-8, colony formation, transwell assay, and xenograft mice model were used to detect effects and regulatory mechanism of circSETD3/miR-423-3p/Bim axis on cell aggressive phenotype and . Here, we identified that circSETD3 downregulated in both HB clinical tissues and cell lines, compared to that of normal tissues and cells. Further gain-of-function experiments validated that circSETD3 overexpression inhibited cell proliferation, viability, migration, epithelial-mesenchymal transition (EMT) and tumorigenesis, and induced cell apoptosis in HB cells. Next, we validated that miR-423-3p targeted both circSETD3 and 3' untranslated region (3'UTR) of Bim, and circSETD3 positively regulated Bim in HB cells through sponging miR-423-3p in a competing endogenous RNA (ceRNA)-dependent manner. Furthermore, through conducting reversal experiments, we evidenced that the inhibiting effects of circSETD3 overexpression on HB development were abrogated by upregulating miR-423-3p and downregulating Bim. Taken together, we evidenced that circSETD3 sponged miR-423-3p to upregulate Bim, resulting in the inhibition of HB development.
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http://dx.doi.org/10.3389/fgene.2021.724197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511783PMC
September 2021

Dynamic Interactions of Transcription Factors and Enhancer Reprogramming in Cancer Progression.

Front Oncol 2021 20;11:753051. Epub 2021 Sep 20.

Department of Molecular Medicine, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.

While improved tumor treatment has significantly reduced the overall mortality rates, invasive progression including recurrence, therapy resistance and metastasis contributes to the majority of deaths caused by cancer. Enhancers are essential distal DNA regulatory elements that control temporal- or spatial-specific gene expression patterns during development and other biological processes. Genome-wide sequencing has revealed frequent alterations of enhancers in cancers and reprogramming of distal enhancers has emerged as one of the important features for tumors. In this review, we will discuss tumor progression-associated enhancer dynamics, its transcription factor (TF) drivers and how enhancer reprogramming modulates gene expression during cancer invasive progression. Additionally, we will explore recent advancements in contemporary technology including single-cell sequencing, spatial transcriptomics and CUT&RUN, which have permitted integrated studies of enhancer reprogramming . Given the essential roles of enhancer dynamics and its drivers in controlling cancer progression and treatment outcome, understanding these changes will be paramount in mitigating invasive events and discovering novel therapeutic targets.
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http://dx.doi.org/10.3389/fonc.2021.753051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488287PMC
September 2021

Advances in research on pharmacotherapy of sarcopenia.

Aging Med (Milton) 2021 Sep 9;4(3):221-233. Epub 2021 Aug 9.

Department of Geriatric Medicine The Central Hospital of Changsha City Changsha China.

Sarcopenia is a comprehensive degenerative disease with the progressive loss of skeletal muscle mass with age, accompanied by the loss of muscle strength and muscle dysfunction. As a new type of senile syndrome, sarcopenia seriously threatens the health of the elderly. The first-line treatment for sarcopenia is exercise and nutritional supplements. However, pharmacotherapy will provide more reliable and sustainable interventions in geriatric medicine. Clinical trials of new drugs targeting multiple molecules are ongoing. This article focuses on the latest progress in pharmacotherapeutic approaches of sarcopenia in recent years by comprehensively reviewing the clinical outcomes of the existing and emerging pharmacotherapies as well as the molecular mechanisms underlying their therapeutic benefits and side effects.
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http://dx.doi.org/10.1002/agm2.12168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444957PMC
September 2021

Pathogens distribution and antimicrobial resistance in bloodstream infections in twenty-five neonatal intensive care units in China, 2017-2019.

Antimicrob Resist Infect Control 2021 08 16;10(1):121. Epub 2021 Aug 16.

Department of Pediatrics, Heze Municipal Hospital, Heze, China.

Background: Overcrowding, abuse of antibiotics and increasing antimicrobial resistance negatively affect neonatal survival rates in developing countries. We aimed to define pathogens and their antimicrobial resistance (AMR) of early-onset sepsis (EOS), hospital-acquired late-onset sepsis (HALOS) and community-acquired late-onset sepsis (CALOS) in 25 neonatal intensive care units (NICUs) in China.

Study Design: This retrospective descriptive study included pathogens and their AMR from all neonates with bloodstream infections (BSIs) admitted to 25 tertiary hospitals in China from January 1, 2017, and December 31, 2019. We defined EOS as the occurrence of BSI at or before 72 h of life and late-onset sepsis (LOS) if BSI occurred after 72 h of life. LOS were classified as CALOS if occurrence of BSI was ≤ 48 h after admission, and HALOS, if occurrence was > 48 h after admission.

Results: We identified 1092 pathogens of BSIs in 1088 infants from 25 NICUs. Thirty-two percent of all pathogens were responsible for EOS, 64.3% HALOS, and 3.7% CALOS. Gram-negative (GN) bacteria accounted for a majority of pathogens in EOS (56.7%) and HALOS (62.2%). The most frequent pathogens causing EOS were Escherichia coli (27.2%) and group B streptococcus (GBS; 14.6%) whereas in CALOS they were GBS (46.3%) and Staphylococcus aureus (41.5%). Klebsiella pneumoniae (27.9%), Escherichia coli (15.7%) and Fungi (12.8%) were the top three isolates in HALOS. Third-generation cephalosporin resistance rates in GN bacteria ranged from 9.7 to 55.6% in EOS and 26% to 63.3% in HALOS. Carbapenem resistance rates in GN bacteria ranged from 2.7 to 31.3% in HALOS and only six isolates in EOS were carbapenem resistant. High rates of multidrug resistance were observed in Klebsiella pneumoniae (60.7%) in HALOS and in Escherichia coli (44.4%) in EOS. All gram-positive bacteria were susceptible to vancomycin except for three Enterococcus faecalis in HALOS. All-cause mortality was higher among neonates with EOS than HALOS (7.4% VS 4.4%, [OR] 0.577, 95% CI 0.337-0.989; P = 0.045).

Conclusions: Escherichia coli, Klebsiella pneumoniae and GBS were the leading pathogens in EOS, HALOS and CALOS, respectively. The high proportion of pathogens and high degree of antimicrobial resistance in HALOS underscore understanding of the pathogenesis and emphasise the need to devise effective interventions in developing countries.
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http://dx.doi.org/10.1186/s13756-021-00989-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365905PMC
August 2021

Towards symbiotic autonomous systems.

Philos Trans A Math Phys Eng Sci 2021 10 16;379(2207):20200359. Epub 2021 Aug 16.

University of Science and Technology, Beijing, People's Republic of China.

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http://dx.doi.org/10.1098/rsta.2020.0359DOI Listing
October 2021

Adaptive neural network control for nonlinear cyber-physical systems subject to false data injection attacks with prescribed performance.

Philos Trans A Math Phys Eng Sci 2021 Oct 16;379(2207):20200372. Epub 2021 Aug 16.

School of Automation and Electrical Engineering, University of Science and Technology Beijing, Beijing 100083, People's Republic of China.

Cyber-physical systems (CPSs), as emerging products of industry [Formula: see text], play a key role in the development of intelligent manufacturing. This paper proposes an observer-based adaptive neural network (NN) control for nonlinear strict-feedback CPSs subject to false data injection attacks. Since there may be strict constraints on the state or output signals of nonlinear cyber-physical systems (NCPSs), we propose a time-varying asymmetric barrier Lyapunov function to realize the specific output constraints of NCPSs under cyber-attacks. Besides, since false data injection attacks will corrupt the transmitted state variables, an observer is designed to obtain observations of the exact states, and NN is used to approximate the unknown nonlinearity of NCPSs. With the proposed control strategy, the constraint control problem of NCPSs subject to false data injection attacks is settled. Finally, a numerical simulation example verifies the effectiveness of the proposed controller. This article is part of the theme issue 'Towards symbiotic autonomous systems'.
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http://dx.doi.org/10.1098/rsta.2020.0372DOI Listing
October 2021

Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation.

Mol Cell 2021 08 9;81(16):3368-3385.e9. Epub 2021 Aug 9.

Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center and UTHealth, Houston, TX 77030, USA. Electronic address:

The mechanistic understanding of nascent RNAs in transcriptional control remains limited. Here, by a high sensitivity method methylation-inscribed nascent transcripts sequencing (MINT-seq), we characterized the landscapes of N6-methyladenosine (m6A) on nascent RNAs. We uncover heavy but selective m6A deposition on nascent RNAs produced by transcription regulatory elements, including promoter upstream antisense RNAs and enhancer RNAs (eRNAs), which positively correlates with their length, inclusion of m6A motif, and RNA abundances. m6A-eRNAs mark highly active enhancers, where they recruit nuclear m6A reader YTHDC1 to phase separate into liquid-like condensates, in a manner dependent on its C terminus intrinsically disordered region and arginine residues. The m6A-eRNA/YTHDC1 condensate co-mixes with and facilitates the formation of BRD4 coactivator condensate. Consequently, YTHDC1 depletion diminished BRD4 condensate and its recruitment to enhancers, resulting in inhibited enhancer and gene activation. We propose that chemical modifications of eRNAs together with reader proteins play broad roles in enhancer activation and gene transcriptional control.
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http://dx.doi.org/10.1016/j.molcel.2021.07.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383322PMC
August 2021

Molecular Survey of Tick-Borne Pathogens Reveals Diversity and Novel Organisms With Veterinary and Public Health Significance in Wildlife From a National Nature Reserve of China.

Front Vet Sci 2021 12;8:682963. Epub 2021 Jul 12.

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.

Wildlife is involved in the maintenance and transmission of various tick-borne pathogens. The objective of the present study was to determine the occurrence and diversity of tick-borne pathogens in free-ranging wild animals collected from Tangjiahe National Nature Reserve of China. Blood or liver samples from 13 wild animals (5 takin, 3 Himalayan goral, 3 Reeves' muntjac, 1 forest musk deer, and 1 wild boar) were collected and screened for piroplasm, spp., spp., and spotted fever group (SFG) rickettsiae by PCR-based on different gene loci. Three species, a potential novel parasite ( sp. T4) and two species were identified in those wildlife. was found in Himalayan goral, Reeves' muntjac, and forest musk deer; , and a potential novel, parasite ( sp. T4), were identified in takin. Meanwhile, was identified in Himalayan goral, takin, Reeves' muntjac, forest musk deer, and wild boar; and related strains was found in takin, Reeves' muntjac, and forest musk deer. All wildlife included in this study was negative for , and SFG rickettsiae. Moreover, coinfection involving spp. and spp. was observed in eight wild animals. This study provided the first evidence of tick-borne pathogens in free-ranging wild animals from the nature reserve, where contact between domestic and wild animals rarely occurs.
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http://dx.doi.org/10.3389/fvets.2021.682963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311164PMC
July 2021

Development of a Potential Penside Colorimetric LAMP Assay Using Neutral Red for Detection of African Swine Fever Virus.

Front Microbiol 2021 23;12:609821. Epub 2021 Apr 23.

State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.

African swine fever (ASF) has caused huge economic losses to the swine industry worldwide. Since there is no commercial ASF vaccine available, an early diagnosis is extremely important to prevent and control the disease. In this study, ASF virus (ASFV) capsid protein-encoding gene (p72) was selected and used to design primers for establishing a one-step visual loop-mediated isothermal amplification (LAMP) assay with neutral red, a pH-sensitive dye, as the color shift indicator. Neutral red exhibited a sharp contrast of color change from faint orange (negative) to pink (positive) during LAMP for detection of ASFV. The designed primer set targeting highly conserved region of the p72 gene was highly specific to ASFV and showed no cross-reactivity with other swine viruses. The detection limit for the one-step visual LAMP developed was 10 copies/reaction based on the recombinant plasmid containing the p72 gene of ASFV. More importantly, the developed one-step visual LAMP showed high consistency with the results of the real-time polymerase chain reaction (qPCR) method recommended by World Organization for Animal Health (OIE). Furthermore, the results demonstrate that the colorimetric detection with this LAMP assay could be directly applied for the whole blood and serum samples without requiring genome extraction. Based on our results, the developed one-step visual LAMP assay is a promising penside diagnostic tool for development of early and cost-effective ASF monitoring program that would greatly contribute to the prevention and control of ASF.
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http://dx.doi.org/10.3389/fmicb.2021.609821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102904PMC
April 2021

Microcalcification-Based Tumor Malignancy Evaluation in Fresh Breast Biopsies with Hyperspectral Stimulated Raman Scattering.

Anal Chem 2021 04 7;93(15):6223-6231. Epub 2021 Apr 7.

State Key Laboratory of Surface Physics and Department of Physics, Human Phenome Institute, Multiscale Research Institute of Complex Systems, Academy for Engineering and Technology, Key Laboratory of Micro and Nano Photonic Structures, Ministry of Education, Fudan University, Shanghai 200433, China.

Precise evaluation of breast tumor malignancy based on tissue calcifications has important practical value in the disease diagnosis, as well as the understanding of tumor development. Traditional X-ray mammography provides the overall morphologies of the calcifications but lacks intrinsic chemical information. In contrast, spontaneous Raman spectroscopy offers detailed chemical analysis but lacks the spatial profiles. Here, we applied hyperspectral stimulated Raman scattering (SRS) microscopy to extract both the chemical and morphological features of the microcalcifications, based on the spectral and spatial domain analysis. A total of 211 calcification sites from 23 patients were imaged with SRS, and the results were analyzed with a support vector machine (SVM) based classification algorithm. With optimized combinations of chemical and geometrical features of microcalcifications, we were able to reach a precision of 98.21% and recall of 100.00% for classifying benign and malignant cases, significantly improved from the pure spectroscopy or imaging based methods. Our findings may provide a rapid means to accurately evaluate breast tumor malignancy based on fresh tissue biopsies.
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http://dx.doi.org/10.1021/acs.analchem.1c00522DOI Listing
April 2021

Pontin Functions as A Transcriptional Co-activator for Retinoic Acid-induced HOX Gene Expression.

J Mol Biol 2021 07 11;433(14):166928. Epub 2021 Mar 11.

Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. Electronic address:

Pontin is a AAA+ ATPase protein that has functions in various biological contexts including gene transcription regulation, chromatin remodeling, DNA damage sensing and repair, as well as assembly of protein and ribonucleoprotein complexes. Pontin is known to regulate the transcription of several important signaling pathways, including Wnt signaling. However, its role in early embryonic signaling regulation remains unclear. Retinoic acid (RA) signaling plays a central role in vertebrate development. Using an in vivo biotin tagging technology, we mapped the genome-wide binding pattern of Pontin before and after RA-induced differentiation in the pluripotent embryo carcinoma cell line NTERA-2. Biotin ChIP-seq revealed significant changes in genome-wide Pontin binding sites upon RA stimulation. We also identified a substantial amount of overlapping binding peaks between Pontin and RARα, especially on all of the HOX gene loci (A-D clusters). Pontin knockdown experiments showed that its chromatin binding at the HOX gene clusters is required for RA-induced HOX gene expression. Furthermore, we performed Global Run-On sequencing (GRO-seq) to map de novo transcripts genome-wide and found that Pontin knockdown significantly diminished nascent HOX gene transcripts, indicating that Pontin regulates HOX gene expression at the transcriptional level. Finally, proteomic analysis demonstrated that Pontin associates with chromatin organization/remodeling complexes and various other functional complexes. Altogether, we have demonstrated that Pontin is a critical transcriptional co-activator for RA-induced HOX gene activation.
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http://dx.doi.org/10.1016/j.jmb.2021.166928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184613PMC
July 2021

African Swine Fever Virus MGF-505-7R Negatively Regulates cGAS-STING-Mediated Signaling Pathway.

J Immunol 2021 04 12;206(8):1844-1857. Epub 2021 Mar 12.

State Key Laboratory of Veterinary Etiological Biology and World Organisation for Animal Health/National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, Gansu, China

African swine fever virus (ASFV) is a devastating infectious disease in pigs, severely threatening the global pig industry. To efficiently infect animals, ASFV must evade or inhibit fundamental elements of the innate immune system, namely the type I IFN response. In this study, we identified that ASFV MGF-505-7R protein exerts a negative regulatory effect on STING-dependent antiviral responses. MGF-505-7R interacted with STING and inhibited the cGAS-STING signaling pathway at STING level. MGF-505-7R overexpression either degraded STING or STING expression was reduced in ASFV-infected cells via autophagy, whereas STING expression was elevated in MGF-505-7R-deficient ASFV-infected cells. We further found that MGF-505-7R promoted the expression of the autophagy-related protein ULK1 to degrade STING, whereas ULK1 was elevated in MGF-505-7R-deficient ASFV-infected cells. Moreover, MGF-505-7R-deficient ASFV induced more IFN-β production than wild-type ASFV and was attenuated in replication compared with wild-type ASFV. The replicative ability of MGF-505-7R-deficient ASFV was also attenuated compared with wild-type. Importantly, MGF-505-7R-deficient ASFV was fully attenuated in pigs. Our results showed for the first time, to our knowledge, a relationship involving the cGAS-STING pathway and ASFV MGF-505-7R, contributing to uncover the molecular mechanisms of ASFV virulence and to the rational development of ASFV vaccines.
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http://dx.doi.org/10.4049/jimmunol.2001110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023146PMC
April 2021

African Swine Fever Virus MGF-110-9L-deficient Mutant Has Attenuated Virulence in Pigs.

Virol Sin 2021 Apr 10;36(2):187-195. Epub 2021 Mar 10.

State Key Laboratory of Veterinary Etiological Biology and OIE/National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.

African swine fever virus (ASFV) is the etiological agent of African swine fever (ASF), an often lethal disease in domestic and wild pigs. ASF represents a major threat to the swine industry worldwide. Currently, no commercial vaccine is available because of the complexity of ASFV or biosecurity concerns. Live attenuated viruses that are naturally isolated or genetically manipulated have demonstrated reliable protection against homologous ASFV strain challenge. In the present study, a mutant ASFV strain with the deletion of ASFV MGF-110-9L (ASFV-Δ9L) was generated from a highly virulent ASFV CN/GS/2018 parental strain, a genotype II ASFV. Relative to the parental ASFV isolate, deletion of the MGF-110-9L gene significantly decreased the ability of ASFV-Δ9L to replicate in vitro in primary swine macrophage cell cultures. The majority of animals inoculated intramuscularly with a low dose of ASFV-Δ9L (10 HAD) remained clinically normal during the 21-day observational period. Three of five ASFV-Δ9L-infected animals displayed low viremia titers and low virus shedding and developed a strong virus-specific antibody response, indicating partial attenuation of the ASFV-Δ9L strain in pigs. The findings imply the potential usefulness of the ASFV-Δ9L strain for further development of ASF control measures.
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http://dx.doi.org/10.1007/s12250-021-00350-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087726PMC
April 2021

Postponing tumor onset and tumor progression can be achieved by alteration of local tumor immunity.

Cancer Cell Int 2021 Feb 10;21(1):97. Epub 2021 Feb 10.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, China.

Background: It has been known for years that the same genetic defects drive breast cancer formation, yet, the onset of breast cancer in different individuals among the same population differs greatly in their life spans with unknown mechanisms.

Methods: We used a MMTV-PyMT mouse model with different genetic backgrounds (FVB/NJ vs. C57BL/6J) to generate different cancer onset phenotypes, then profiled and analyzed the gene expression of three tumor stages in both Fvb.B6 and Fvb mice to explore the underlying mechanisms.

Results: We found that in contrast with the FVB/N-Tg (MMTV-PyMT) 634Mul mice (Fvb mice), mammary tumor initiation was significantly delayed and tumor progression was significantly suppressed in the Fvb.B6 mice (generated by crossing FVB/NJ with C57BL/6J mice). Transcriptome sequencing and analysis revealed that the differentially expressed genes were enriched in immune-related pathways. Flow cytometry analysis showed a higher proportion of matured dendritic cells in the Fvb.B6 mice. The plasma levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) were significantly reduced in the Fvb.B6 mice. IL-6 also impaired the maturation of bone marrow dendritic cells (BMDCs) of the Fvb mice in vitro.

Conclusion: All these findings suggest that immunity levels (characterized by a reduced IL-6 level and intact DC maturation in Fvb.B6 mice) are the key factors affecting tumor onset in a murine mammary cancer model.
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http://dx.doi.org/10.1186/s12935-021-01765-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874464PMC
February 2021

Identification and evaluation of midgut protein RL12 of Dermacentor silvarum interacting with Anaplasma ovis VirD4.

Ticks Tick Borne Dis 2021 05 27;12(3):101677. Epub 2021 Jan 27.

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, Gansu, 730046, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, PR China. Electronic address:

Anaplasma ovis, a tick-borne intra-erythrocytic Gram-negative bacterium, is a causative agent of ovine anaplasmosis. It is known that Dermacentor ticks act as biological vectors for A. ovis. VirD4 is the machine component of Type IV Secretion System of A. ovis. To better understand the pathogen-vector interaction, VirD4 was used as a bait protein for screening midgut proteins of Dermacentor silvarum via yeast two-hybrid mating assay. As a result, a ribosomal protein RL12 was identified from the midgut cDNA library of D. silvarum. For further validation, using in vitro Glutathione S-transferase (GST) pull-down assay, interaction between the proteins, GST-RL12 and HIS-VirD4, was observed in Western blot analysis. The study is first of its kind reporting a D. silvarum midgut protein interaction with VirD4 from A. ovis. Functional annotations showed some important cellular processes are attributed to the protein, particularly in the stringent response and biogenesis. The results of the study suggest the involvement of the VirD4-RL12 interaction in the regulation of signaling pathways, which is a tool for understanding the pathogen-vector interaction.
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http://dx.doi.org/10.1016/j.ttbdis.2021.101677DOI Listing
May 2021

[Comparison of the antigenicity of African swine fever virus p35 protein as diagnostic antigen].

Sheng Wu Gong Cheng Xue Bao 2021 Jan;37(1):187-195

State Key Laboratory of Veterinary Etiological Biology/Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, Gansu, China.

In order to screen African swine fever virus (ASFV) diagnostic antigen with the best enzyme linked immunosorbent assay (ELISA) reactivity. By establishing the ELISA method, the diagnostic antigen of ASFV p30 protein expressed by baculovirus-insect cell expression system as reference, we explored the antigenic properties and diagnostic potential of ASFV p35 protein expressed by prokaryotic expression system as a diagnostic antigen. The results of Western blotting and immunofluorescence show that the molecular weight of the recombinant p35 protein and p30 protein obtained was 40 kDa and 30 kDa, respectively, and these two proteins had good immuno-reactivity with ASFV positive serum. Recombinant p30 and p35 proteins were used as diagnostic antigens to establish ELISA, and the sensitivity and repeatability of these methods were tested. The results show that although the detection sensitivity of the p30-ELISA established in this study was higher than that of the p35-ELISA, the sensitivity of p35-ELISA was 95.8%, and variations in intra- and inter-assay repeatability of the two methods were less than 10%. The coincidence rate between the p35-ELISA and the imported kit was 97.2%. Results show that p35-ELISA was sensitive and stable, and could detect specific antibodies against ASFV.
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http://dx.doi.org/10.13345/j.cjb.200359DOI Listing
January 2021

Vibration Control for Flexible Manipulators With Event-Triggering Mechanism and Actuator Failures.

IEEE Trans Cybern 2021 Jan 8;PP. Epub 2021 Jan 8.

This article focuses on flexible single-link manipulators (FSLMs) under boundary control and in-domain control. The actuators of the system include the dc motor at the end of the joint and m piezoelectric controllers installed at the flexible link, which is regarded as an Euler-Bernoulli beam. The problem of the infinite number of actuator failures, including the partial loss of the effectiveness and total loss of effectiveness, is solved by the adaptive compensation method. By introducing the relative threshold strategy, the event-triggered control (ETC) scheme is proposed to achieve angle regulation and vibration suppression while reducing the communication burden between the controllers and the actuators. The Lyapunov direct method is utilized to prove that the system is uniformly ultimately bounded and both the angular tracking error and elastic displacement converge to a neighborhood of zero. Numerical simulation results are provided to demonstrate the effectiveness of the proposed control law.
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http://dx.doi.org/10.1109/TCYB.2020.3041727DOI Listing
January 2021

Axon Injury-Induced Autophagy Activation Is Impaired in a Model of Tauopathy.

Int J Mol Sci 2020 Nov 13;21(22). Epub 2020 Nov 13.

Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.

Autophagy is a conserved pathway that plays a key role in cell homeostasis in normal settings, as well as abnormal and stress conditions. Autophagy dysfunction is found in various neurodegenerative diseases, although it remains unclear whether autophagy impairment is a contributor or consequence of neurodegeneration. Axonal injury is an acute neuronal stress that triggers autophagic responses in an age-dependent manner. In this study, we investigate the injury-triggered autophagy response in a model of tauopathy. We found that transgenic expression of pro-aggregant Tau, but not the anti-aggregant Tau, abolished axon injury-induced autophagy activation, resulting in a reduced axon regeneration capacity. Furthermore, axonal trafficking of autophagic vesicles were significantly reduced in the animals expressing pro-aggregant F3ΔK280 Tau, indicating that Tau aggregation impairs autophagy regulation. Importantly, the reduced number of total or trafficking autophagic vesicles in the tauopathy model was not restored by the autophagy activator rapamycin. Loss of PTL-1, the sole Tau homologue in , also led to impaired injury-induced autophagy activation, but with an increased basal level of autophagic vesicles. Therefore, we have demonstrated that Tau aggregation as well as Tau depletion both lead to disruption of injury-induced autophagy responses, suggesting that aberrant protein aggregation or microtubule dysfunction can modulate autophagy regulation in neurons after injury.
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http://dx.doi.org/10.3390/ijms21228559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696692PMC
November 2020

Hexavalent chromium amplifies the developmental toxicity of graphene oxide during zebrafish embryogenesis.

Ecotoxicol Environ Saf 2021 Jan 28;208:111487. Epub 2020 Oct 28.

School of Public Health, Xinxiang Medical University, Xinxiang 453003, China.

Combined toxicity is a critical issue in risk assessment of contaminants. However, very little is known about the joint effects of graphene oxide (GO, a crucial 2-dimensional carbon material) and hexavalent chromium (Cr, a widespread heavy metal), particularly with respect to the critical period of embryogenesis. In this study, the combined toxicity of GO and Cr was evaluated through embryo-larval toxicity test in Danio rerio (zebrafish). Results indicated that the co-exposure of Cr (1 mg/L) and GO (0.01 mg/L) inhibited hatching and spontaneous movement of embryos, but no significant changes were found in the single Cr or GO group. Compared with the single GO or Cr exposure, their co-exposure (GO+Cr) significantly enhanced the teratogenicity in a concentration-dependent pattern, and the spinal curvature was observed as the main deformity. GO+Cr changed the protein secondary structures of embryos result of the generation of ROS and oxidative stress. The degradations of vertical myosepta and cartilages were observed in co-exposure group, suggesting that GO+Cr disrupted the development of musculoskeletal system. The genes col11a1a, col2a1a and postnb were down-regulated but the genes acta1b and mmp9 were up-regulated by GO+Cr. The interactions between Cr and GO demonstrated that the morphology, structure, and surface properties of GO were modified by Cr. The enhanced defects and O-containing groups of GO could trap more β-sheets, induced oxidative stress, disturbed the development of skeletal muscles and cartilages in zebrafish. These data suggested that GO+Cr enhanced their joint toxicity due to the variation of nanoparticle properties. This finding is important for assessing the ecological risk of graphene family nanomaterials in the natural environment.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111487DOI Listing
January 2021

Pathogenesis and multidisciplinary management of medication-related osteonecrosis of the jaw.

Int J Oral Sci 2020 10 21;12(1):30. Epub 2020 Oct 21.

The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of bone-modifying agents and inhibits angiogenesis agents. Although the pathogenesis of MRONJ is not entirely clear, multiple factors may be involved in specific microenvironments. The TGF-β1 signalling pathway may have a key role in the development of MRONJ. According to the clinical stage, multiple variables should be considered when selecting the most appropriate treatment. Therefore, the prevention and management of treatment of MRONJ should be conducted in patient-centred multidisciplinary team collaborative networks with oncologists, dentists and dental specialists. This would comprise a closed responsibility treatment loop with all benefits directed to the patient. Thus, in the present review, we aimed to summarise the pathogenesis, risk factors, imaging features, clinical staging, therapeutic methods, prevention and treatment strategies associated with MRONJ, which may provide a reference that can inform preventive strategies and improve the quality of life for patients in the future.
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http://dx.doi.org/10.1038/s41368-020-00093-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578793PMC
October 2020

Hit-to-lead optimization and discovery of a potent, and orally bioavailable G protein coupled receptor kinase 2 (GRK2) inhibitor.

Bioorg Med Chem Lett 2020 12 7;30(23):127602. Epub 2020 Oct 7.

Discovery Sciences, Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, United States.

G-protein coupled receptor kinase 2 (GRK2), which is upregulated in the failing heart, appears to play a critical role in heart failure (HF) progression in part because enhanced GRK2 activity promotes dysfunction of β-adrenergic signaling and myocyte death. An orally bioavailable GRK2 inhibitor could offer unique therapeutic outcomes that cannot be attained by current heart failure treatments that directly target GPCRs or angiotensin-converting enzyme. Herein, we describe the discovery of a potent, selective, and orally bioavailable GRK2 inhibitor, 8h, through high-throughput screening, hit-to-lead optimization, structure-based design, molecular modelling, synthesis, and biological evaluation. In the cellular target engagement assays, 8h enhances isoproterenol-mediated cyclic adenosine 3',5'-monophosphate (cAMP) production in HEK293 cells overexpressing GRK2. Compound 8h was further evaluated in a human stem cell-derived cardiomyocyte (HSC-CM) contractility assay and potentiated isoproterenol-induced beating rate in HSC-CMs.
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http://dx.doi.org/10.1016/j.bmcl.2020.127602DOI Listing
December 2020

Menin and Menin-Associated Proteins Coregulate Cancer Energy Metabolism.

Cancers (Basel) 2020 Sep 22;12(9). Epub 2020 Sep 22.

Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.

The interplay between glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) is central to maintain energy homeostasis. It remains to be determined whether there is a mechanism governing metabolic fluxes based on substrate availability in microenvironments. Here we show that menin is a key transcription factor regulating the expression of OXPHOS and glycolytic genes in cancer cells and primary tumors with poor prognosis. A group of menin-associated proteins (MAPs), including KMT2A, MED12, WAPL, and GATA3, is found to restrain menin's full function in this transcription regulation. shRNA knockdowns of menin and MAPs result in reduced ATP production with proportional alterations of cellular energy generated through glycolysis and OXPHOS. When shRNA knockdown cells are exposed to metabolic stress, the dual functionality can clearly be distinguished among these metabolic regulators. A MAP can negatively counteract the regulatory mode of menin for OXPHOS while the same protein positively influences glycolysis. A close-proximity interaction between menin and MAPs allows transcriptional regulation for metabolic adjustment. This coordinate regulation by menin and MAPs is necessary for cells to rapidly adapt to fluctuating microenvironments and to maintain essential metabolic functions.
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http://dx.doi.org/10.3390/cancers12092715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564175PMC
September 2020

Phase transition enhanced superior elasticity in freestanding single-crystalline multiferroic BiFeO membranes.

Sci Adv 2020 Aug 21;6(34). Epub 2020 Aug 21.

Electronic Materials Research Laboratory, Key Laboratory of the Ministry of Education, School of Electronic and Information Engineering, Center for Spintronics and Quantum System, State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.

The integration of ferroic oxide thin films into advanced flexible electronics will bring multifunctionality beyond organic and metallic materials. However, it is challenging to achieve high flexibility in single-crystalline ferroic oxides that is considerable to organic or metallic materials. Here, we demonstrate the superior flexibility of freestanding single-crystalline BiFeO membranes, which are typical multiferroic materials with multifunctionality. They can endure cyclic 180° folding and have good recoverability, with the maximum bending strain up to 5.42% during in situ bending under scanning electron microscopy, far beyond their bulk counterparts. Such superior elasticity mainly originates from reversible rhombohedral-tetragonal phase transition, as revealed by phase-field simulations. This study suggests a general fundamental mechanism for a variety of ferroic oxides to achieve high flexibility and to work as smart materials in flexible electronics.
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http://dx.doi.org/10.1126/sciadv.aba5847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442355PMC
August 2020

Echo-Tracking Technique in Ultrasonography Can Monitor Changes in Carotid Artery Elastic Function at Early Stage of Intensity-Modulated Radiation Therapy for Nasopharyngeal Carcinoma.

Med Sci Monit 2020 Sep 9;26:e926260. Epub 2020 Sep 9.

Department of Radiotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland).

BACKGROUND We used echo-tracking (ET) technique to observe short-term dynamic changes of the carotid artery in nasopharyngeal carcinoma (NPC) patients after intensity-modulated radiation therapy (IMRT). MATERIAL AND METHODS Sixty-one NPC patients received IMRT. In the irradiation group, the carotid artery was examined by ultrasonography before radiotherapy, at 2, 4, and 6 weeks after the start of radiotherapy, and at 3 and 6 months after the end of radiotherapy. In the control group, the carotid artery was examined by ultrasonography before radiotherapy of patients in the irradiation group, and at 3 and 6 months after the end of radiotherapy of patients in the irradiation group. RESULTS During radiotherapy for the 61 patients, the maximum dose on the carotid artery was 65.14±4.35 Gy, the average dose was 57.46±4.12 Gy, and the 50% volume dose was 51.80±5.32 Gy. At the end of irradiation, Ep (kPa) and ß values were significantly different from those before treatment. CONCLUSIONS The present study demonstrates that the elastic function of the carotid artery can be significantly affected when the irradiation dose exceeds 45 Gy.
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http://dx.doi.org/10.12659/MSM.926260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501737PMC
September 2020

Author Correction: Prediction of disulfide bond engineering sites using a machine learning method.

Sci Rep 2020 Jul 28;10(1):12942. Epub 2020 Jul 28.

Complex Systems Division, Beijing Computational Science Research Center, 8 E Xibeiwang Rd, Haidian, Beijing, 100193, People's Republic of China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-69841-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385647PMC
July 2020

Sensitivity analysis and optimization of optical Y-branch structure parameters.

Appl Opt 2020 Jul;59(19):5803-5811

Aimed at the structural parameters in the new optical Y-branch, this paper uses the Morris screening method and Sobol method in global sensitivity analysis to analyze the sensitivity of each parameter when the input optical field introduces an offset. The sensitivity parameters of the optical Y-branch are selected, and global sensitivity analysis of the sensitivity parameters is performed. The results of sensitivity analysis improve the parameter optimization process of the optical Y-branch. Finally, the optical Y-branch is optimized to obtain a small insertion loss, good uniformity, low wavelength-dependent loss, and polarization-dependent loss.
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http://dx.doi.org/10.1364/AO.391749DOI Listing
July 2020
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