Publications by authors named "Teng Liu"

203 Publications

Whole-genome resequencing identified candidate genes associated with the number of ribs in Hu sheep.

Genomics 2021 May 11;113(4):2077-2084. Epub 2021 May 11.

College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, Gansu 730070, China. Electronic address:

The number of ribs is an important economic trait in the sheep industry when the sheep are raised for mutton. However, in sheep, the genetic mechanisms regulating rib number are poorly understood. In the present study, we aimed to identify important candidate genes that affect the increase in rib number in sheep. Whole-genome resequencing of 36 Hu sheep with an increased number of ribs (R14) and 36 sheep with normal (R13) rib numbers was carried out. Analysis using three methods (fixation index (F), Fisher's exact test, and Chi-squared test) showed that 219 single nucleotide polymorphism sites overlapped among the results of the three methods, which represented 206 genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that the genes were mainly associated with regulation of developmental process, inorganic anion transport, cellular biosynthetic process, tight junction, the oxytocin signaling pathway, and arrhythmogenic right ventricular cardiomyopathy. Four mutations were selected according to the significantly selected genomic regions and important pathways for genotyping and association analysis. The result demonstrated that three synonymous mutations correlated significantly with the rib number. Importantly, we revealed that the CPOX (encoding coproporphyrinogen oxidase), KCNH1 (encoding potassium voltage-gated channel subfamily H member 1), and CPQ (encoding carboxypeptidase Q) genes have a combined effect on rib number in Hu sheep. Our results identified candidate molecular markers for rib number in sheep breeding.
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http://dx.doi.org/10.1016/j.ygeno.2021.05.004DOI Listing
May 2021

Exogenous 1',4'--Diol-ABA Induces Stress Tolerance by Affecting the Level of Gene Expression in Tobacco ( L.).

Int J Mol Sci 2021 Mar 4;22(5). Epub 2021 Mar 4.

CAS Key Laboratory of Environmental and Applied Microbiology, Environmental Microbiology Key Laboratory of Sichuan Province, Innovation Academy for Seed Design, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.

1',4'--diol-ABA is a key precursor of the biosynthesis of abscisic acid (ABA) biosynthesis in fungi. We successfully obtained the pure compound from a mutant of and explored its function and possible mechanism on plants by spraying 2 mg/L 1',4'--diol-ABA on tobacco leaves. Our results showed that this compound enhanced the drought tolerance of tobacco seedlings. A comparative transcriptome analysis showed that a large number of genes responded to the compound, exhibiting 1523 genes that were differentially expressed at 12 h, which increased to 1993 at 24 h and 3074 at 48 h, respectively. The enrichment analysis demonstrated that the differentially expressed genes (DEGs) were primarily enriched in pathways related to hormones and resistance. The DEGs of transcription factors were generally up-regulated and included the bHLH, bZIP, ERF, MYB, NAC, WRKY and HSF families. Moreover, the levels of expression of PYL/PYR, PP2C, SnRK2, and ABF at the ABA signaling pathway responded positively to exogenous 1',4'--diol-ABA. Among them, seven ABF transcripts that were detected were significantly up-regulated. In addition, the genes involved in salicylic acid, ethylene and jasmonic acid pathways, reactive oxygen species scavenging system, and other resistance related genes were primarily induced by 1',4'--diol-ABA. These findings indicated that treatment with 1',4'--diol-ABA could improve tolerance to plant abiotic stress and potential biotic resistance by regulating gene expression, similar to the effects of exogenous ABA.
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http://dx.doi.org/10.3390/ijms22052555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961390PMC
March 2021

Multi-modal artificial dura for simultaneous large-scale optical access and large-scale electrophysiology in non-human primate cortex.

J Neural Eng 2021 Apr 14;18(5). Epub 2021 Apr 14.

Department of Electrical and Computer Engineering, University of Washington, Seattle, WA, United States of America.

Non-human primates (NHPs) are critical for development of translational neural technologies because of their neurological and neuroanatomical similarities to humans. Large-scale neural interfaces in NHPs with multiple modalities for stimulation and data collection poise us to unveil network-scale dynamics of both healthy and unhealthy neural systems. We aim to develop a large-scale multi-modal interface for NHPs for the purpose of studying large-scale neural phenomena including neural disease, damage, and recovery.We present a multi-modal artificial dura (MMAD) composed of flexible conductive traces printed into transparent medical grade polymer. Our MMAD provides simultaneous neurophysiological recordings and optical access to large areas of the cortex (∼3 cm) and is designed to mitigate photo-induced electrical artifacts. The MMAD is the centerpiece of the interfaces we have designed to support electrocorticographic recording and stimulation, cortical imaging, and optogenetic experiments, all at the large-scales afforded by the brains of NHPs. We performed electrical and optical experiments bench-side andwith macaques to validate the utility of our MMAD.Using our MMAD we present large-scale electrocorticography from sensorimotor cortex of three macaques. Furthermore, we validated surface electrical stimulation in one of our animals. Our bench-side testing showed up to 90% reduction of photo-induced artifacts with our MMAD. The transparency of our MMAD was confirmed both via bench-side testing (87% transmittance) and viaimaging of blood flow from the underlying microvasculature using optical coherence tomography angiography.Our results indicate that our MMAD supports large-scale electrocorticography, large-scale cortical imaging, and, by extension, large-scale optical stimulation. The MMAD prepares the way for both acute and long-term chronic experiments with complimentary data collection and stimulation modalities. When paired with the complex behaviors and cognitive abilities of NHPs, these assets prepare us to study large-scale neural phenomena including neural disease, damage, and recovery.
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http://dx.doi.org/10.1088/1741-2552/abf28dDOI Listing
April 2021

Effects of water-nitrogen coupling on photosynthetic characteristics, yield, water and nitrogen use efficiency for mountain apple trees under surge-root irrigation in Northern Shaanxi area of China.

Ying Yong Sheng Tai Xue Bao 2021 Mar;32(3):967-975

State Key Laboratory Base of Eco-Hydraulics in Northwest Arid Region, Xi'an University of Technology, Xi'an 710048, China.

Taking 7-year-old apple trees (Hanfu) as the test material, an experiment with three irrigation levels including high water (W, 85%-100%, was the field water holding capacity), medium water (W, 70%-85%) and low water (W, 55%-70%), and three nitrogen application levels, high (N, 600 kg·hm), medium (N, 400 kg·hm) and low (N, 200 kg·hm), was conducted to investigate the effects of water and nitrogen coupling on photosynthetic characteristics, yield and water and nitrogen utilization of apple trees in mountainous areas under surge-root irrigation (SRI). The results showed that the net photosynthetic rate (), transpiration rate (), stomatal conductance (), intercellular CO concentration (), leaf instantaneous water use efficiency (WUE) of apple trees leaves decreased with decreasing nitrogen application rates under the same irrigation amount, but increased. Under the same nitrogen application rate, foliar , , and WUE decreased with decreasing irrigation amount, but increased. The daily average values of and under WN treatment were the largest, while WN treatment had the largest WUE. Apple yield, irrigation water use efficiency (IWUE) and nitrogen partial productivity (NPFP) were significantly affected by irrigation and nitrogen application. The WN treatment had the highest yield (26761 kg·hm). IWUE increased significantly with the decreasing irrigation and the increasing nitrogen application, while NPFP increased significantly with the increases of irrigation and the decreases of nitrogen application. Results of the regression analysis showed that the combination of irrigation and nitrogen application was closest to WN treatment when yield and IWUE got the optimal solution. Therefore, WN treatment was the best combination mode of water and nitrogen application for apple under SRI in Northern Shaanxi mountain area.
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http://dx.doi.org/10.13287/j.1001-9332.202103.027DOI Listing
March 2021

Identification of a novel protein in porcine astrovirus that is important for virus replication.

Vet Microbiol 2021 Apr 11;255:108984. Epub 2021 Jan 11.

College of Animal Science and Technology, Guangxi University, No.100 Daxue Road, Nanning 530005, China. Electronic address:

Overlapping genes are common in some RNA viruses. It has been proposed that a potential overlapping gene is the ORFX, here termed ORF2b, which overlaps the ORF2 coding sequence in astroviruses. The aim of this study was to determine whether ORF2b is an overlapping gene that encodes a functional protein which is needed for viral replication. Sequence alignment showed that there was an ORF2b in a PAstV type 1 strain of astrovirus, PAstV1-GX1, which was embedded within the larger ORF2. The AUG codon for ORF2b is located 19 nucleotides downstream of the initiation site of ORF2 and contains 369 nucleotides and it codes for a predicted 122-amino-acid protein. A specific polyclonal antibody against the ORF2b protein was raised and used to demonstrate the expression of the new identified gene in virus-infected and pCAGGS-ORF2b-transfected cells. Analysis of purified virions revealed that the ORF2b protein was not incorporated into virus particles. Reverse genetics based on a PAstV type 1 infectious cDNA clone showed that the ORF2b protein was not essential but important for optimal virus infectivity. Knockout of the downstream potential stop codon candidate of ORF2b demonstrated that the C-terminus of the ORF2b protein can be extended by 170 amino acids, suggesting that the C-terminus of the newly identified ORF2b protein may be variable.
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http://dx.doi.org/10.1016/j.vetmic.2021.108984DOI Listing
April 2021

miR-324-3p reverses cisplatin resistance by inducing GPX4-mediated ferroptosis in lung adenocarcinoma cell line A549.

Biochem Biophys Res Commun 2021 Apr 1;549:54-60. Epub 2021 Mar 1.

Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, PR China. Electronic address:

Purpose: MicroRNAs act as crucial regulators of a diverse range of biological processes, including chemoresistance. Our study aimed to investigate the effect of miR-324-3p on lung adenocarcinoma cell line A549 resistant to cis-diamminedichloroplatinum II (DDP, aka cisplatin).

Methods: The miR-324-3p expression levels in cisplatin-sensitive A549(A549) and cisplatin-resistant A549 (A549/DDP) cells were determined by qRT-PCR assay. Cell proliferation was determined with the commercial kit CCK-8 and colony formation assay, whereas cell death was analyzed using flow cytometry. The target gene of miR-324-3p was identified and validated with the luciferase reporter and western blot assays. The role of miR-324-3p in modulating cisplatin resistance was evaluated in vitro.

Results: The expression of miR-324-3p was found to be significantly downregulated in the A549/DDP cells. Conversely, miR-324-3p overexpression reversed cisplatin resistance in the cells. With regard to the possible mechanism underlying this phenomenon, we identified the glutathione peroxidase 4 (GPX4) gene as the direct target of miR-324-3p, where overexpression of the gene reversed the miR-324-3p effect of sensitizing the A549/DDP cells to cisplatin. Furthermore, the GPX4 inhibitor RSL3 could mimic the effect of miR-324-3p upregulation in increasing the sensitivity of the cisplatin-resistant cells to the drug. Significantly, miR-324-3p enhanced cisplatin-induced ferroptosis in the A549/DDP cells.

Conclusion: Our findings revealed the role of the miR-324-3p-GPX4 signaling axis in A549/DDP cells and how the targeting of this axis could be a potential strategy for reversing cisplatin resistance in human non small cell lung cancer (NSCLC).
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http://dx.doi.org/10.1016/j.bbrc.2021.02.077DOI Listing
April 2021

A folate receptor 3 SNP promotes mitochondria-induced clonogenicity of CML leukemia cells: Implications for treatment free remission.

Clin Transl Med 2021 Feb;11(2):e317

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.1002/ctm2.317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862584PMC
February 2021

Versatile labeling of multiple radionuclides onto a nanoscale metal-organic framework for tumor imaging and radioisotope therapy.

Biomater Sci 2021 Apr 24;9(8):2947-2954. Epub 2021 Feb 24.

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, Jiangsu, China.

Radionuclides for cancer theranostic have confronted problems such as limitation in real-time visualization and unsatisfactory therapeutic effect sacrificed by the nonspecific distribution. Nanoscale metal-organic frameworks (nMOFs) have been widely used in biomedical applications including cancer imaging and drug delivery. However, there have been rare reports utilizing nMOFs as a single nanoplatform to label various radionuclides for tumor imaging and radioisotope therapy (RIT). In this work, we developed polyethylene glycol (PEG) modified zirconium-based nMOFs (PCN-224) with favorable size, water solubility and biocompatibility. Interestingly, without the help of chelating agents, metal radionuclides (technetium-99 m/Tc, lutetium-177/Lu) could be efficiently labeled onto nMOFs via chelating with the porphyrin structure and iodine-125 (I) via chemical substitution of hydrogen in the benzene ring. The radionuclide-labeled PCN-PEG nanoparticles all exhibit excellent radiolabeling stability in different solutions. In accordance with the fluorescence imaging of mice injected with PCN-PEG, SPECT/CT imaging illustrates strong tumor accumulation of Tc-PCN-PEG. Moreover, Lu-PCN-PEG significantly inhibited the growth of tumor without inducing any perceptible toxicity to the treated mice. Hence, the radionuclide-delivery nanoplatform based on nMOFs would provide more opportunities for precise tumor theranostics and expand the biomedical applications of MOF nanomaterials.
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http://dx.doi.org/10.1039/d0bm02225jDOI Listing
April 2021

Antiviral activity and mechanism of ESC-1GN from skin secretion of hylarana guentheri against influenza a virus.

J Biochem 2021 Feb 24. Epub 2021 Feb 24.

Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.

Development of new and effective anti-influenza drugs is critical for prophylaxis and treatment of influenza A virus infection. A wide range of amphibian skin secretions have been identified to show antiviral activity. Our previously reported ESC-1GN, a peptide from the skin secretion of Hylarana guentheri, displayed good antimicrobial and anti-inflammatory effects. Here, we found that ESC-1GN possessed significant antiviral effects against influenza A viruses. Moreover, ESC-1GN could inhibit the entry of divergent H5N1 and H1N1 virus strains with the IC50 values from 1.29 to 4.59 μM. Mechanism studies demonstrated that ESC-1GN disrupted membrane fusion activity of influenza A viruses by interaction with HA2 subunit. The results of site-directed mutant assay and molecular docking revealed that E105, N50 and the residues around them on HA2 subunit could form hydrogen bonds with amino acid on ESC-1GN, which were critical for ESC-1GN binding to HA2 and inhibiting the entry of influenza A viruses. Altogether, these not only suggest that ESC-1GN maybe represent a new type of excellent template designing drugs against influenza A viruses, but also it may shed light on the immune mechanism and survival strategy of H. guentheri against viral pathogens.
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http://dx.doi.org/10.1093/jb/mvab019DOI Listing
February 2021

In situ preparation of highly dispersed Pd supported on exfoliated layered double hydroxides via nitrogen plasma for 4-nitrophenol reduction.

Environ Sci Pollut Res Int 2021 Feb 13. Epub 2021 Feb 13.

School of Chemistry and Material Sciences, Heilongjiang University, Harbin, 150080, People's Republic of China.

In this work, a simple and environmental-friendly nitrogen glow discharge plasma reduction method has been developed for synthesizing palladium nanoparticles (PdNPs) supported on exfoliated Mg-Al-layered double hydroxide (Pd/LDH) catalysts. The as-prepared catalysts were characterized by means of characterizations methods, which contain X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectrometry (XPS), and Fourier transform infrared (FT-IR). Highly dispersed ultrafine PdNPs were supported on exfoliated, defect-induced LDHs uniformly without agglomeration. The effects of treatment time of nitrogen plasma and Pd loading amount on structure, morphology, and catalytic performance of Pd/LDHs were investigated. The comparisons of structure and morphology between LDHs and Pd/LDHs were also discussed. The average particle size of as-synthesized PdNPs with face-centered cubic structure is 2.01 nm, which ranges from 1.18 to 3.01 nm. Nitrogen plasma cannot only reduce Pd, but also exfoliate LDHs, introduce defects, and even destroy the structure of LDHs. The Pd/LDH catalyst with 1 wt% Pd loading under nitrogen plasma treatment for 60 min showed the best catalytic performance in 4-nitrophenol reduction. The turnover frequency (TOF) of as-prepared catalyst is 20-fold higher than that of commercial Pd/C catalyst.
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http://dx.doi.org/10.1007/s11356-021-12689-0DOI Listing
February 2021

The pan-cancer lncRNA MILIP links c-Myc to p53 repression.

Mol Cell Oncol 2020 Dec 14;8(1):1842714. Epub 2020 Dec 14.

School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, Australia.

We have recently identified the MYC proto-oncogene, bHLH transcription factor (MYC, best known as c-Myc)-responsive pan-cancer lncRNA c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP) as an oncogenic driver. Our studies show that MILIP facilitates tumor protein p53 (TP53, best known as p53) turnover by reducing its SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2), thus promoting cell survival, proliferation, and tumorigenicity. MILIP may thus represent an anti-cancer target for counteracting the c-Myc axis.
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http://dx.doi.org/10.1080/23723556.2020.1842714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849729PMC
December 2020

The first Hermansky-Pudlak syndrome type 9 patient with two novel variants in Chinese population.

J Dermatol 2021 May 4;48(5):676-680. Epub 2021 Feb 4.

Department of Dermatology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Hermansky-Pudlak syndrome 9 (HPS-9) is a recessive disorder caused by BLOC1S6 gene. There are only four variants identified from four HPS-9 patients so far. Here, we reported the first HPS-9 patient in a Chinese population. He had brownish-yellow hair, white skin, brown irises with visual acuity, photophobia and nystagmus. Two novel variants, c.148G>T (p.Glu50*) and c.351dupT (p.Ile118Tyrfs*10) in BLOC1S6 gene were identified by whole-exome sequencing (WES). Absence of platelet dense granules was found by whole-mount platelet electron microscopy and Western blotting assays showed the destabilized BLOC-1 subunits. He had recurrent bruising and was found to have abnormal brain waves by electroencephalogram, but did not develop thrombopenia, immunodeficiency or other symptoms reported in other HPS-9 patients. This is the first case report of BLOC-1 mutation in a Chinese population and our findings expand the mutational spectrum of HPS genes.
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http://dx.doi.org/10.1111/1346-8138.15762DOI Listing
May 2021

A zinc transporter, transmembrane protein 163, is critical for the biogenesis of platelet dense granules.

Blood 2021 Apr;137(13):1804-1817

Beijing Key Laboratory for Genetics of Birth Defects/Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Genetics and Birth Defects Control Center/National Center for Children's Health, and Beijing Children's Hospital/Capital Medical University, Beijing, China.

Lysosome-related organelles (LROs) are a category of secretory organelles enriched with ions such as calcium, which are maintained by ion transporters or channels. Homeostasis of these ions is important for LRO biogenesis and secretion. Hermansky-Pudlak syndrome (HPS) is a recessive disorder with defects in multiple LROs, typically platelet dense granules (DGs) and melanosomes. However, the underlying mechanism of DG deficiency is largely unknown. Using quantitative proteomics, we identified a previously unreported platelet zinc transporter, transmembrane protein 163 (TMEM163), which was significantly reduced in BLOC-1 (Dtnbp1sdy and Pldnpa)-, BLOC-2 (Hps6ru)-, or AP-3 (Ap3b1pe)-deficient mice and HPS patients (HPS2, HPS3, HPS5, HPS6, or HPS9). We observed similar platelet DG defects and higher intracellular zinc accumulation in platelets of mice deficient in either TMEM163 or dysbindin (a BLOC-1 subunit). In addition, we discovered that BLOC-1 was required for the trafficking of TMEM163 to perinuclear DG and late endosome marker-positive compartments (likely DG precursors) in MEG-01 cells. Our results suggest that TMEM163 is critical for DG biogenesis and that BLOC-1 is required for the trafficking of TMEM163 to putative DG precursors. These new findings suggest that loss of TMEM163 function results in disruption of intracellular zinc homeostasis and provide insights into the pathogenesis of HPS or platelet storage pool deficiency.
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http://dx.doi.org/10.1182/blood.2020007389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020268PMC
April 2021

Extracellular vesicles deposit to rejuvenate aged bone marrow-derived mesenchymal stem cells and slow age-related degeneration.

Sci Transl Med 2021 Jan;13(578)

Center for Artificial Intelligence Biology, Hubei Bioinformatics and Molecular Imaging Key Laboratory, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.

Stem cell senescence increases alongside the progressive functional declines that characterize aging. The effects of extracellular vesicles (EVs) are now attracting intense interest in the context of aging and age-related diseases. Here, we demonstrate that neonatal umbilical cord (UC) is a source of EVs derived from mesenchymal stem cells (MSC-EVs). These UC-produced MSC-EVs (UC-EVs) contain abundant anti-aging signals and rejuvenate senescing adult bone marrow-derived MSCs (AB-MSCs). UC-EV-rejuvenated AB-MSCs exhibited alleviated aging phenotypes and increased self-renewal capacity and telomere length. Mechanistically, UC-EVs rejuvenate AB-MSCs at least partially by transferring proliferating cell nuclear antigen () into recipient AB-MSCs. When tested in therapeutic context, UC-EV-triggered rejuvenation enhanced the regenerative capacities of AB-MSCs in bone formation, wound healing, and angiogenesis. Intravenously injected UC-EVs conferred anti-aging phenotypes including decreased bone and kidney degeneration in aged mice. Our findings reveal that UC-EVs are of high translational value in anti-aging intervention.
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http://dx.doi.org/10.1126/scitranslmed.aaz8697DOI Listing
January 2021

Kinetically Controllable Pd-Catalyzed Decarboxylation Enabled [5 + 2] and [3 + 2] Cycloaddition toward Carbocycles Featuring Quaternary Carbons.

Org Lett 2021 Jan 6;23(2):351-357. Epub 2021 Jan 6.

Frontier Institute of Science and Technology (FIST), Xi'an Jiaotong University, Xi'an710045, China.

A decarboxylative protocol has been developed toward a range of carbocycles. The key success is based on the use of a batch of newly designed cyclic carbonates as substrates that can provide carbon-carbon zwitterion intermediate under palladium catalysis. The kinetics of the reactions are controllable toward either strained seven- or thermodynamically more favored five-membered carbocycles. The release of this chemistry will shed light on the synthesis of complex and valuable cyclic structures.
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http://dx.doi.org/10.1021/acs.orglett.0c03856DOI Listing
January 2021

Bixin Attenuates Experimental Autoimmune Encephalomyelitis by Suppressing TXNIP/NLRP3 Inflammasome Activity and Activating NRF2 Signaling.

Front Immunol 2020 9;11:593368. Epub 2020 Dec 9.

Clinical Medical College, The First Affiliated Hospital, Collaborative Innovation Center of Sichuan for Elderly Care and Health of Chengdu Medical College, Chengdu, China.

Multiple sclerosis (MS), an autoimmune and degenerative disease, is characterized by demyelination and chronic neuroinflammation. Bixin is a carotenoid isolated from the seeds of that exhibits various potent pharmacological activities, including antioxidant, anti-inflammatory, and anti-tumor properties. However, the effects of bixin on MS have not yet been examined. To evaluate the effects and underlying molecular mechanisms of bixin on MS, experimental autoimmune encephalomyelitis (EAE) was established in C57BL/6 mice, which were treated intragastric administration of bixin solutions. To evaluate the molecular mechanisms of bixin, quantitative reverse-transcription PCR, western blot, immunohistochemistry, flow cytometry, and enzyme-linked immunosorbent assay analyses were performed. We found that bixin significantly improved the symptoms and pathology in EAE mice, reduced the release of inflammatory cytokines TNF-α, IL-6, IL-8, IL-17, and IFN-γ, and increased the expression of the anti-inflammatory cytokine IL-10. And bixin reduced the proportion of Th1 and Th17 cells in the spleen and CNS, and suppressed microglia aggregation, and TXNIP/NLRP3 inflammasome activity by scavenging excessive reactive oxygen species (ROS) in EAE mice. Furthermore, bixin inhibited inflammation and oxidative stress activating nuclear factor erythroid 2-related factor 2 (NRF2), and its downstream genes in EAE mice, meanwhile, these effects were suppressed upon treatment with an NRF2 inhibitor, ML385. Bixin prevented neuroinflammation and demyelination in EAE mice primarily by scavenging ROS through activation of the NRF2 signaling pathway. Taken together, our results indicate that bixin is a promising therapeutic candidate for treatment of MS.
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http://dx.doi.org/10.3389/fimmu.2020.593368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756000PMC
December 2020

HPS1 Regulates the Maturation of Large Dense Core Vesicles and Lysozyme Secretion in Paneth Cells.

Front Immunol 2020 5;11:560110. Epub 2020 Nov 5.

Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Genetics and Birth Defects Control Center, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.

HPS1, a BLOC-3 subunit that acts as a guanine nucleotide exchange factor of Rab32/38, may play a role in the removal of VAMP7 during the maturation of large dense core vesicles of Paneth cells. Loss of HPS1 impairs lysozyme secretion and alters the composition of intestinal microbiota, which may explain the susceptibility of HPS-associated inflammatory bowel disease. Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, bleeding tendency, and other chronic organ lesions due to defects in tissue-specific lysosome-related organelles (LROs). For some HPS subtypes, such as HPS-1, it is common to have symptoms of HPS-associated inflammatory bowel disease (IBD). However, its underlying mechanism is largely unknown. HPS1 is a subunit of the BLOC-3 complex which functions in the biogenesis of LROs. Large dense core vesicles (LDCVs) in Paneth cells of the intestine are a type of LROs. We here first report the abnormal LDCV morphology (increased number and enlarged size) in HPS1-deficient () mice. Similar to its role in melanosome maturation, HPS1 plays an important function in the removal of VAMP7 from LDCVs to promote the maturation of LDCVs. The immature LDCVs in mice are defective in regulated secretion of lysozyme, a key anti-microbial peptide in the intestine. We observed changes in the composition of intestinal microbiota in both HPS-1 patients and mice. These findings provide insights into the underlying mechanism of HPS-associated IBD development, which may be implicated in possible therapeutic intervention of this devastating condition.
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http://dx.doi.org/10.3389/fimmu.2020.560110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674556PMC
November 2020

Amifostine ameliorates induction of experimental autoimmune encephalomyelitis: Effect on reactive oxygen species/NLRP3 pathway.

Int Immunopharmacol 2020 Nov 22;88:106998. Epub 2020 Sep 22.

Clinical Laboratory, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, 278 Baoguang Road, Chengdu, Sichuan 610500, PR China; Collaborative Innovation Center of Sichuan for Elderly Care and Health of Chengdu Medical College, Baoguang Road, Chengdu, Sichuan 610041, PR China. Electronic address:

Multiple sclerosis (MS) is an autoimmune disease for which conventional treatments have limited efficacy or side effects. Free radicals are primarily involved in blood-brain barrier disruption and induce neuronal and axonal damage, thus promoting the development of MS. Amifostine, a radioprotective drug used as a cytoprotective agent, attenuates oxidative stress and improves radiation damage by acting as a direct scavenger of reactive oxygen and nitrogen species. The aim of this study was to evaluate the effects of amifostine on MS in a mouse model of experimental autoimmune encephalomyelitis (EAE), which was developed by immunizing C57BL/6 mice with myelin oligodendrocyte glycoprotein and pertussis toxin. EAE mice received intraperitoneal injections of amifostine prior to onset of clinical symptoms and were monitored up to day 15 post induction. We observed abnormal clinical behavioral scores and a decrease in body weight. Histological analysis showed severe inflammatory infiltration and demyelination in the brain and spinal cord lumbar enlargements where significant upregulation of the mRNA expression of the pro-inflammatory cytokines interleukin-6 and interleukin-8, downregulation of the anti-inflammatory cytokine interleukin-10, and obvious microgliosis were also observed. Amifostine treatment potently reversed these abnormal changes. The anti-inflammatory effect of amifostine was associated with the inhibition of reactive oxygen species generation. Furthermore, the expression of proteins involved in the NLRP3 signaling pathway and pyroptosis was decreased. In conclusion, our study showed that amifostine ameliorates induction of experimental autoimmune encephalomyelitis via anti-inflammatory and anti-pyroptosis effects, providing further insights into the use of amifostine for the treatment of MS.
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http://dx.doi.org/10.1016/j.intimp.2020.106998DOI Listing
November 2020

Differential Expression of Viral Transcripts From Single-Cell RNA Sequencing of Moderate and Severe COVID-19 Patients and Its Implications for Case Severity.

Front Microbiol 2020 16;11:603509. Epub 2020 Oct 16.

Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, United States.

With steady increase of new COVID-19 cases around the world, especially in the United States, health care resources in areas with the disease outbreak are quickly exhausted by overwhelming numbers of COVID-19 patients. Therefore, strategies that can effectively and quickly predict the disease progression and stratify patients for appropriate health care arrangements are urgently needed. We explored the features and evolutionary difference of viral gene expression in the SARS-CoV-2 infected cells from the bronchoalveolar lavage fluids of patients with moderate and severe COVID-19 using both single cell and bulk tissue transcriptome data. We found SARS-CoV-2 sequences were detectable in 8 types of immune related cells, including macrophages, T cells, and NK cells. We first reported that the SARS-CoV-2 ORF10 gene was differentially expressed in the severe vs. moderate samples. Specifically, ORF10 was abundantly expressed in infected cells of severe cases, while it was barely detectable in the infected cells of moderate cases. Consequently, the expression ratio of ORF10 to nucleocapsid (N) was significantly higher in severe than moderate cases ( = 0.0062). Moreover, we found transcription regulatory sequences (TRSs) of the viral leader sequence-independent fusions with a 5' joint point at position 1073 of SARS-CoV-2 genome were detected mainly in the patients with death outcome, suggesting its potential indication of clinical outcome. Finally, we identified the motifs in TRS of the viral leader sequence-dependent fusion events of SARS-CoV-2 and compared with that in SARS-CoV, suggesting its evolutionary trajectory. These results implicated potential roles and predictive features of viral transcripts in the pathogenesis of COVID-19 moderate and severe patients. Such features and evolutionary patterns require more data to validate in future.
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http://dx.doi.org/10.3389/fmicb.2020.603509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596306PMC
October 2020

Handheld swept-source optical coherence tomography guided by smartphone-enabled wide-field autofluorescence photography for imaging facial sebaceous glands.

Opt Lett 2020 Oct;45(20):5704-5707

We report a method to image facial sebaceous glands (SGs) using smartphone-enabled wide-field autofluorescence photography (AFP) and handheld swept-source optical coherence tomography (SS-OCT). Smartphone-enabled AFP provides a 2D wide-field fluorescence image that is used both as a functional mapping of the sebum and a positioning guidance for OCT imaging of the SG. Following the guidance, handheld SS-OCT conducts the volume scan to investigate depth-resolved conditions of the SG in the selected regions of interest. We show the results from smartphone-enabled AFP and handheld SS-OCT to demonstrate the ability of our method to image facial SGs, potentially useful for the assessment of skin conditions in dermatology and cosmetology.
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http://dx.doi.org/10.1364/OL.405765DOI Listing
October 2020

N-methyladenosine-dependent pri-miR-17-92 maturation suppresses PTEN/TMEM127 and promotes sensitivity to everolimus in gastric cancer.

Cell Death Dis 2020 10 9;11(10):836. Epub 2020 Oct 9.

Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.

N-methyladenosine (mA) is the most common epigenetic RNA modification with essential roles in cancer progression. However, roles of mA and its regulator METTL3 on non-coding RNA in gastric cancer are unknown. In this study, we found elevated levels of mA and METTL3 in gastric cancer. Increased METTL3 expression indicated poor outcomes of patients and high malignancy in vitro and in vivo. Mechanically, mA facilitated processing of pri-miR-17-92 into the miR-17-92 cluster through an mA/DGCR8-dependent mechanism. The mA modification that mediated this process occurred on the A879 locus of pri-miR-17-92. The miR-17-92 cluster activated the AKT/mTOR pathway by targeting PTEN or TMEM127. Compared with those with low levels of METTL3, METTL3-high tumors showed preferred sensitivity to an mTOR inhibitor, everolimus. These results reveal a perspective on epigenetic regulations of non-coding RNA in gastric cancer progression and provide a theoretical rationale for use of everolimus in the treatment of mA/METTL3-high gastric cancer.
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http://dx.doi.org/10.1038/s41419-020-03049-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547657PMC
October 2020

c-Myc inactivation of p53 through the pan-cancer lncRNA MILIP drives cancer pathogenesis.

Nat Commun 2020 10 5;11(1):4980. Epub 2020 Oct 5.

Translational Research Institute, Henan Provincial People's Hospital and People's Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University, Zhengzhou, 450053, Henan, China.

The functions of the proto-oncoprotein c-Myc and the tumor suppressor p53 in controlling cell survival and proliferation are inextricably linked as "Yin and Yang" partners in normal cells to maintain tissue homeostasis: c-Myc induces the expression of ARF tumor suppressor (p14 in human and p19 in mouse) that binds to and inhibits mouse double minute 2 homolog (MDM2) leading to p53 activation, whereas p53 suppresses c-Myc through a combination of mechanisms involving transcriptional inactivation and microRNA-mediated repression. Nonetheless, the regulatory interactions between c-Myc and p53 are not retained by cancer cells as is evident from the often-imbalanced expression of c-Myc over wildtype p53. Although p53 repression in cancer cells is frequently associated with the loss of ARF, we disclose here an alternate mechanism whereby c-Myc inactivates p53 through the actions of the c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP). MILIP functions to promote p53 polyubiquitination and turnover by reducing p53 SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2). MILIP upregulation is observed amongst diverse cancer types and is shown to support cell survival, division and tumourigenicity. Thus our results uncover an inhibitory axis targeting p53 through a pan-cancer expressed RNA accomplice that links c-Myc to suppression of p53.
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http://dx.doi.org/10.1038/s41467-020-18735-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536215PMC
October 2020

NTCP Deficiency Causes Gallbladder Abnormalities in Mice and Human Beings.

Cell Mol Gastroenterol Hepatol 2021 9;11(3):831-839. Epub 2020 Sep 9.

National Institute of Biological Sciences, Beijing, China; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China. Electronic address:

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http://dx.doi.org/10.1016/j.jcmgh.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851344PMC
September 2020

Honokiol-Chlorambucil Co-Prodrugs Selectively Enhance the Killing Effect through STAT3 Binding on Lymphocytic Leukemia Cells and .

ACS Omega 2020 Aug 29;5(31):19844-19852. Epub 2020 Jul 29.

Institute of Chinese Medicine, Hunan Academy of Traditional Chinese Medicine&Innovation Centre for Science and Technology, Hunan University of Chinese Medicine, Changsha 410208, PR China.

The broad-spectrum DNA alkylating therapeutic, chlorambucil (CBL), has limited safety and shows lower therapy effect because of a short half-life while used in the clinic. Therefore, it is very necessary to develop a more efficient and safer type of CBL derivate against tumors with selective targeting of cancer cells. In addition, the natural product of honokiol (HN), the novel potent chemo-preventive or therapeutic entity/carrier, can target the mitochondria of cancer cells through STAT3 to prevent cancer from spreading and metastasizing. In this study, we designed and synthesized the honokiol-chlorambucil (HN-CBL) co-prodrugs through carbonate ester linkage conjugating with the targeted delivery help of the HN skeleton in cancer cells. Biological evaluation indicated that HN-CBL can remarkably enhance the antiproliferation of human leukemic cell lines CCRF-CEM, Jurkat, U937, MV4-11, and K562. Furthermore, HN-CBL can also selectively inhibit the lymphocytic leukemia (LL) cell survival compared to those mononuclear cells derived from healthy donors (PBMCs), enhance mitochondrial activity in leukemia cells, and induce LL cell apoptosis. Molecular docking and western blot study showed that HN-CBL can also bind with the STAT3 protein at some hydrophobic residues and downregulate the phosphorylation level of STAT3-like HN. Significantly, HN-CBL could dramatically delay leukemia growth with no observable physiological toxicity. Thus, HN-CBL may provide a novel and effective targeting therapeutic against LL with fewer side effects.
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http://dx.doi.org/10.1021/acsomega.0c02832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424726PMC
August 2020

Effects of nonylphenol induced oxidative stress on apoptosis and autophagy in rat ovarian granulosa cells.

Chemosphere 2020 Dec 23;261:127693. Epub 2020 Jul 23.

Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China. Electronic address:

Nonylphenol (NP) is a kind of environmental endocrine disruptors which is generally recognized to cause female reproductive toxicity, but its basic mechanism has not been fully elucidated. In this study, granulosa cells (GCs) were treated with 0-70 μM NP for 24 h, the cell viability of GCs was reduced significantly, as well as increased cell apoptosis with G2/M arrest. Furthermore, NP significantly induced autophagy and the production of reactive oxygen species (ROS). However, these phenomenons were inhibited by blocking the production of ROS with N-Acetyl-l-cysteine (NAC) administration. Intriguingly, the inhibition of autophagy with 3-Methyladenine (3-MA) could enhance the apoptosis induced by NP. Moreover, the down regulating of p-Akt/Akt, p-mTOR/mTOR and subsequent up-regulation of p-AMPK/AMPK induced by NP can be rescued by pretreatment of NAC. Our findings suggested that NP promotes rat ovarian GCs apoptosis and autophagy simultaneously, which may involve the activation of ROS-dependent Akt/AMPK/mTOR pathway. Whatever, the activation of autophagy is likely to develop a protective mechanism to improve the apoptosis of rat ovarian GCs induced by NP.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127693DOI Listing
December 2020

Genetic variants and mutational spectrum of Chinese Hermansky-Pudlak syndrome patients.

Pigment Cell Melanoma Res 2021 01 17;34(1):111-121. Epub 2020 Aug 17.

Department of Dermatology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Hermansky-Pudlak syndrome (HPS) is a rare recessive disorder characterized by oculocutaneous albinism or ocular albinism, bleeding diathesis, and other symptoms such as colitis and pulmonary fibrosis. Eleven causative genes have been identified for HPS-1-HPS-11 subtypes in humans. We have identified 16 newly reported patients including the first HPS-2 case in the Chinese population. In a total of 40 HPS patients, hypopigmentation was milder in HPS-3, HPS-5, and HPS-6 patients than in HPS-1 and HPS-4 patients. HPS-1 accounted for 47.5% (19 of 40) of HPS cases which is the most common subtype. Exons 11 and 19 were the hotspots of the HPS1 gene mutations. In total, 55 allelic variants were identified in HPS1-HPS6 gene, of which 17 variants were previously unreported. These results will be useful for the evaluation of the relationship between HPS genotypes and phenotypes, and for the precise intervention of HPS patients in the Chinese population.
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http://dx.doi.org/10.1111/pcmr.12916DOI Listing
January 2021

RNAseq profiling of circRNA expression in radiation-treated A549 cells and bioinformatics analysis of radiation-related circRNA-miRNA networks.

Oncol Lett 2020 Aug 5;20(2):1557-1566. Epub 2020 Jun 5.

Clinical Laboratory, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China.

With the development of new biochemical and computational methods, circular RNAs (circRNAs) have been identified as microRNA sponges. circRNAs are associated with many diseases, particularly cancer. The present study aimed to investigate the expression profile of circRNAs in irradiated A549 lung cancer cells using high-throughput sequencing. Bioinformatics analyses were used to examine the potential functions of circRNAs. RNA sequencing data demonstrated that 1,875 circRNA targets were differentially expressed in A549 cells in response to irradiation. A total of 30 circRNAs were upregulated and 37 circRNAs were downregulated significantly in irradiation-treated A549 cells (fold change ≥2.0; P<0.05). The top 5 upregulated and downregulated circRNAs were successfully validated by reverse transcription-quantitative PCR. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that differentially expressed circRNAs might be pivotal in biological irradiation responses to irradiation. circRNA-microRNA co-expression networks highlighted the biological significance of circRNA_0002174 and circRNA_0036627, which require further study. In conclusion, the present study is, to the best of the authors' knowledge, the first to describe the differentially expressed profile of circRNAs in response to irradiation in A549 cells. These results provide a new perspective to elucidate insight into the molecular mechanisms by which A549 cells respond to radiation, and a basis for a more in-depth analysis of the potential application of circRNAs in the treatment of lung cancer therapy.
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http://dx.doi.org/10.3892/ol.2020.11698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377113PMC
August 2020

Prognostic Significance of Elevated Preoperative Serum CA125 Levels After Curative Hepatectomy for Hepatocellular Carcinoma.

Onco Targets Ther 2020 22;13:4559-4567. Epub 2020 May 22.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, People's Republic of China.

Objective: The aim of this study was to investigate predictive and prognostic significance of elevated carbohydrate antigen 125 (CA125) serum level preoperatively.

Methods: A total of 3440 HCC patients were retrospectively enrolled into this study, and all of them underwent curative hepatectomy. The clinical and pathological variables together with CA125, AFP serum level were collected at diagnosis and postoperative care stages. A chi-square test was used to compare the differences between variables. Overall survival (OS) and recurrence-free survival (RFS) were measured with the Kaplan-Meier method. To estimate prognostic factors, a multivariate Cox regression analysis was performed.

Results: Of the 3440 enrolled patients, 409 (11.9%) exhibited elevated preoperative serum CA125 level, and high preoperative serum CA125 level was significantly associated with younger age, female, higher ALBI grade, higher serum AFP level, blood transfusion, more operative bleeding loss, larger tumor size, multiple tumor, increased macro- or micro-vascular invasion, Edmondson grade III-IV, absence of tumor capsular, satellite nodules, liver cirrhosis, more advanced TNM stages and BCLC stages. HCC patients with high preoperative serum CA125 level usually had a shorter OS rate and experienced a higher probability of recurrence than those with normal preoperative serum level of CA125 (p<0.0001). The multivariate analysis suggested that elevated serum CA125 level serves as an independent predictor of OS and RFS in HCC patients after surgical resection.

Conclusion: Elevated preoperative serum CA125 correlated with many malignant characterizations of HCC and served as an independent prognostic factor of OS and RFS.
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http://dx.doi.org/10.2147/OTT.S236475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250700PMC
May 2020