Publications by authors named "Bo Sun"

1,083 Publications

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Leucine, but not isoleucine or valine, affects serum lipid profiles and browning of WAT in mice.

Food Funct 2021 Jun 22. Epub 2021 Jun 22.

College of Animal Science and Veterinary Medicine, Jinzhou Medical University, Jinzhou, Liaoning 121001, China.

Branched chain amino acids (BCAA), especially leucine (Leu), have been reported to decrease fat deposition. However, opposite effects of BCAA on lipid metabolism have been observed. To determine the role of BCAA in lipid metabolism, an amino acid-defined diet was formulated and C57BL/6J mice were assigned into the following groups: amino acid-defined control diet and control diet supplemented with Leu, isoleucine, or valine. Nitrogen was balanced by proportionally mixed amino acids except BCAA. Results showed that dietary Leu supplementation significantly increased the levels of serum triglycerides, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and urea nitrogen. Metabolomics showed that biosynthesis of unsaturated fatty acids was altered by Leu supplementation. Leu treatment up-regulated the expression of genes related to fat synthesis and down-regulated the expression of genes related to fatty acid synthesis. Furthermore, the genes and proteins of selective markers involved in browning of white adipose tissue (WAT) were up-regulated by dietary supplementation with Leu. This study indicated that dietary supplementation with Leu, but not isoleucine or valine, significantly affected lipid metabolism by regulating lipid metabolism-related genes and serum fatty acid concentration, providing a new tool in the management of obesity and metabolic disorders.
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http://dx.doi.org/10.1039/d1fo00341kDOI Listing
June 2021

ATE1 inhibits liver cancer progression through RGS5-mediated suppression of Wnt/β-catenin signaling.

Mol Cancer Res 2021 Jun 22. Epub 2021 Jun 22.

liver Cancer Laboratory, Department of Surgery, Xiangya Hospital Central South University

Arginyltransferase (ATE1) plays critical roles in many biological functions including cardiovascular development, angiogenesis, adipogenesis, muscle contraction, and metastasis of cancer. However, the role of ATE1 in hepatocellular carcinoma (HCC) remains unknown. In this study, we find that ATE1 plays an essential role in growth and malignancy of liver cancer. ATE1 expression is significantly reduced in human HCC samples compared to normal liver tissue. Additionally, low ATE1 expression is correlated with aggressive clinicopathological features and is an independent poor prognostic factor for overall survival and disease-free survival of HCC patients. Lentivirus-mediated ATE1 knockdown significantly promoted liver cancer growth, migration and disease progression in vitro and in vivo. Opposing results were observed when ATE1 was up-regulated. Mechanistically, ATE1 accelerated the degradation of β-catenin and inhibited Wnt signaling by regulating turnover of Regulator Of G Protein Signaling 5 (RGS5). Loss- and gain-of-function assays confirmed that RGS5 was a key effector of ATE1-mediated regulation of Wnt signaling. Further studies indicated that RGS5 might be involved in regulating the activity of GSK3-β, a crucial component of the cytoplasmic destruction complex. Treatment with a GSK inhibitor (CHIR99021) cooperated with ablation of ATE1 or RGS5 overexpression to promote Wnt/β-catenin signaling, but overexpression of ATE1 or RGS5 knockdown did not reverse the effect of GSK inhibitor. Implications: ATE1 inhibits liver cancer progression by suppressing Wnt/β-catenin signaling and can serve as a potentially valuable prognostic biomarker for HCC.
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http://dx.doi.org/10.1158/1541-7786.MCR-21-0027DOI Listing
June 2021

A Combinative Assembly Strategy Inspired Reversibly Borate-Bridged Polymeric Micelles for Lesion-Specific Rapid Release of Anti-Coccidial Drugs.

Nanomicro Lett 2020 Jul 25;12(1):155. Epub 2020 Jul 25.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China.

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http://dx.doi.org/10.1007/s40820-020-00495-1DOI Listing
July 2020

Investigation and Highly Accurate Prediction of Missed Tryptic Cleavages by Deep Learning.

J Proteome Res 2021 Jun 17. Epub 2021 Jun 17.

Biomedical Center, Protein Analysis Unit, Faculty of Medicine, Ludwig-Maximilians-Universität München, Großhaderner Strasse 9, 82152 Planegg-Martinsried, Germany.

Trypsin is one of the most important and widely used proteolytic enzymes in mass spectrometry (MS)-based proteomic research. It exclusively cleaves peptide bonds at the C-terminus of lysine and arginine. However, the cleavage is also affected by several factors, including specific surrounding amino acids, resulting in frequent incomplete proteolysis and subsequent issues in peptide identification and quantification. The accurate annotations on missed cleavages are crucial to database searching in MS analysis. Here, we present deep-learning predicting missed cleavages (dpMC), a novel algorithm for the prediction of missed trypsin cleavage sites. This algorithm provides a very high accuracy for predicting missed cleavages with area under the curves (AUCs) of cross-validation and holdout testing above 0.99, along with the mean F1 score and the Matthews correlation coefficient (MCC) of 0.9677 and 0.9349, respectively. We tested our algorithm on data sets from different species and different experimental conditions, and its performance outperforms other currently available prediction methods. In addition, the method also provides a better insight into the detailed rules of trypsin cleavages coupled with propensity and motif analysis. Moreover, our method can be integrated into database searching in the MS analysis to identify and quantify mass spectra effectively and efficiently.
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http://dx.doi.org/10.1021/acs.jproteome.1c00346DOI Listing
June 2021

CircRNA CircRIMS is Overexpressed in Esophageal Squamous Cell Carcinoma and Downregulate miR-613 Through Methylation to Increase Cell Proliferation.

Cancer Manag Res 2021 9;13:4587-4595. Epub 2021 Jun 9.

Department of Gastroenterology, General Hospital of Eastern Theater Command, Nanjing City, Jiangsu Province, 210002, People's Republic of China.

Purpose: CircRNA CircRIMS has been characterized as an oncogenic circRNA in gastric cancer, while its role in other cancers is unknown. This study aimed to explore the role of CircRIMS in esophageal squamous cell carcinoma (ESCC).

Patients And Methods: Tissues collected from 60 ESCC patients were subjected to extractions of total RNA and RT-qPCRs to analyze the differential expression of CircRIMS and miR-613. The 60 ESCC patients were followed up for 5 years to analyze the prognostic value of CircRIMS for ESCC. The interaction between CircRIMS and miR-613 was showed by luciferase activity assay and fluorescence in situ hybridization. The role of CircRIMS in regulating miR-613 expression and methylation was analyzed by overexpression experiments, RT-qPCRs and Western blot assay. The role of CircRIMS and miR-613 in regulating cell proliferation was analyzed using the BrdU assay. ESCC xenograft model was used to demonstrate the role of CircRIMS and miR-613 in vivo.

Results: We found that CircRIMS was overexpressed in ESCC and predicted poor survival. In addition, miR-613 was under expressed in ESCC and inversely correlated with CircRIMS. In ESCC cells, CircRIMS overexpression decreased the expression of miR-613 and increased the methylation of miR-613 gene. Cell proliferation assay showed that CircRIMS overexpression reduced the inhibitory effects of miR-613 overexpression on cell proliferation. Animal experience finally illustrated that CircRNA CircRIMS downregulated miR-613 through methylation to promote tumor growth.

Conclusion: Therefore, CircRIMS may downregulate miR-613 through methylation to increase cell proliferation in ESCC.
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http://dx.doi.org/10.2147/CMAR.S282983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200154PMC
June 2021

circHIPK3 (hsa_circ_0000284) Promotes Proliferation, Migration and Invasion of Breast Cancer Cells via miR-326.

Onco Targets Ther 2021 9;14:3671-3685. Epub 2021 Jun 9.

The 2nd Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.

Purpose: circHIPK3 has carcinogenic or anti-tumor effects on different cancers. However, there is no relevant research showing whether circHIPK3 was involved in breast cancer (BCa). In this research, the aim was to analyze the function and possible molecular mechanism of circHIPK3 in BCa.

Methods: The expression of circHIPK3 in human BCa tissues and cells was detected by real-time quantitative PCR (RT-qPCR). CircInteractome and dual-luciferase assays were performed to detect circRNA-miRNA targeting relationship. Ribonuclease R treatment, RT-qPCR, Western blot and immunohistochemistry were performed to determine the stability, expressions, abundance of target genes. Loss-of-function or gain-of-function experiments were used to analyze the effects of circHIPK3 and miR-326 on BCa in vivo and in vitro. In vitro, MCF7 and BT20 cells were transfected with circHIPK3 or sicircHIPK3 or miR-326 mimic; in vivo, female BALB/c mice were subcutaneously injected with MCF7 cells (transfected with CirchipK3 or miR-326 mimic) to establish xenograft models.

Results: The circular structure of circHIPK3 was abundantly expressed in the cytoplasm and was up-regulated in BCa. Silenced circHIPK3 suppressed malignant phenotype of BCa cells. MiR-326 interacted with circHIPK3 and the two were negatively correlated. Overexpressed circHIPK3 promoted cell viability, proliferation, migration and invasion, but inhibited apoptosis. Moreover, overexpressed circHIPK3 promoted the expressions of EMT-related genes and antiapoptotic genes, but inhibited proapoptotic gene expressions. Overexpressed circHIPK3 promoted tumor growth and Ki-67 levels, inhibited apoptosis in vivo. The above mentioned effects of circHIPK3 were reversed by miR-326 in vitro or in vivo.

Conclusion: circHIPK3 promoted proliferation, migration and invasion of BCa cells through regulating miR-326.
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http://dx.doi.org/10.2147/OTT.S299190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200520PMC
June 2021

Replication protein A plays multifaceted roles complementary to specialized helicases in processing G-quadruplex DNA.

iScience 2021 May 1;24(5):102493. Epub 2021 May 1.

State Key Laboratory of Crop Stress Biology for Arid Areas and College of Life Sciences, Northwest A&F University, Yangling, Shaanxi 712100, China.

G-quadruplexes (G4s) are non-canonical DNA structures with critical roles in DNA metabolisms. To resolve those structures that can cause replication fork stalling and genomic instability, single-stranded DNA-binding proteins and helicases are required. Here, we characterized the interplay between RPA and helicases on G4s using single-molecule FRET. We first discovered that human RPA efficiently prevents G4 formation by preempting ssDNA before its folding. RPA also differentially interacts with the folded G4s. However, helicases such as human BLM and yeast Pif1 have different G4 preferences from RPA mainly based on loop lengths. More importantly, both RPA and these helicases are required for the stable G4 unfolding, as RPA promotes helicase-mediated repetitive unfolding into durative linear state. Furthermore, BLM can traverse G4 obstacles temporarily disrupted by RPA and continue to unwind downstream duplex. We finally proposed the mechanisms underlying above functions of RPA in preventing, resolving, and assisting helicases to eliminate G4s.
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http://dx.doi.org/10.1016/j.isci.2021.102493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169993PMC
May 2021

Polysaccharides from Ganoderma Sinense - rice bran fermentation products and their anti-tumor activities on non-small-cell lung cancer.

BMC Complement Med Ther 2021 Jun 10;21(1):169. Epub 2021 Jun 10.

Academy of National Food and Strategic Reserves Administration, Beijing, 100037, P. R. China.

Background: Non-small-cell lung cancer (NSCLC) accounts more than 80% of the lung cancer cases. Polysaccharides in rice bran and its fermentation products have been proven to suppress many cancers. However, the report on inhibiting NSCLC is few. In this paper, the polysaccharides with suppression activity to H1299 NSCLC in the fermentation products of full-fat rice bran and defatted rice bran were studied in vitro and in vivo.

Method: Polysaccharides (GSRBPs) were extracted from Ganoderma sinense - full-fat rice bran (GS-FRB) and Ganoderma sinense - defatted rice bran (GS-DRB) fermentation products. The structure information of the GSRBPs was studied using HPLC analysis. The anti-tumor activities on H1299 NSCLC of GSRBPs in vitro study was performed using MTT method. The in vivo studies use BALB/c-nu nude mice as H1299 NSCLC bearing mice.

Result: All the polysaccharides contained two fractions, GSFPS-1 and GSFPS-2. The molecular weight and the ratio of GSFPS-1 and GSFPS-2 were different in GS-FRB and GS-DRB. At the earlier state of fermentation, all polysaccharides were composed of D-glu, D-man, D-xyl and L-ara with certain molar ratios. But at the latter stage, polysaccharides in GS-FRB were composed of D-glu, D-man, D-xyl, L-ara and D-fru, while these in GS-DRB only composed of D-glu and D-man. In the in vitro study, the IC50 of RBS and GSRBPs was as GS-DRB-11 (40.62 μg/mL), GS-FRB-9 (43.82 μg/mL), GS-DRB-7 (48.08 μg/mL), RBS (49.56 μg/mL), GS-DRB-9 (49.91 μg/mL), GS-DRB-13 (51.89 μg/mL), GS-FRB-11 (53.75 μg/mL), GS-FRB-7 (56.84 μg/mL), GS-DRB-13 (60.63 μg/mL) from small to large. In the in vivo study, the H1299 NSCLC inhibition rate (InRa) of RBS and GSRBPs were GS-DRB-11 (86.81%) > GS-DRB-9 (86.01%) > GS-FRB-9 (84.88%) > GS-DRB-7 (82.21%) > GS-DRB-13 (78.04%) > RBS (76.06%) > GS-FRB-13 (65.44%) > GS-FRB-11 (64.70%) > GS-FRB-7 (27.87%). The GSFPS-2 area percent was negatively correlated to the IC50 and was positively correlated to the InRa. This means the GSFPS-2 had much higher anti-tumor activity than GSFPS-1.

Conclusion: GSFPS-2 had higher anti-tumor activities, and the lipid in the rice bran has a decisive effect on the structures of polysaccharides produced by fermentation. Therefore, GSRBPs could be considered as potential novel agents to suppress H1299 non-small-cell lung cancer.
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http://dx.doi.org/10.1186/s12906-021-03346-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194173PMC
June 2021

Derivation and validation of thresholds of cadmium, chromium, lead, mercury and arsenic for safe rice production in paddy soil.

Ecotoxicol Environ Saf 2021 Sep 7;220:112404. Epub 2021 Jun 7.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008, China. Electronic address:

Cadmium (Cd), chromium (Cr), lead (Pb), mercury (Hg) and arsenic (As) are potent toxicants to human health via dietary intake. It is imperative to establish accurate soil thresholds based on soil-plant transfer models and food safety standards for safe agricultural production. This study takes rice genotypes and soil properties into account to derive soil thresholds for five heavy metal(loid)s using the bioconcentration factors (BCF) and species sensitivity distribution (SSD) based on the food safety standard. The BCF generated from two paddy soils was calculated to investigate the sensitivity of heavy metal accumulation in nine rice cultivars in a greenhouse pot experiment. Then, empirical soil-plant transfer models were developed from a middle-sensitivity rice cultivar (Denong 2000, one selected from nine rice) grown in nineteen paddy soils with various soil properties under a proper exogenously metal(loid)s concentration gradient. After normalization, hazardous concentrations from the fifth percentile (HC5) were calculated from the SSD curves, and the derived soil thresholds were obtained from HC5 prediction models that based on the combination of pH and organic carbon (OC) or cation exchange capacity (CEC). The soil Cd threshold derived based on pH and organic carbon (pH < 7.5, OC ≥ 20 g kg) was 1.3-fold of those only considering pH, whereas the Pb threshold (pH > 6, CEC ≥ 20 cmol kg) was 3.1 times lower than the current threshold. The derived thresholds for five elements were validated to be reliable through literature data and field experiments. The results suggested that deriving soil heavy metal(loid)s threshold using SSD method and local food safety standards is feasible and also applicable to other crops as well as other regions with potential health risks of toxic elements contamination in agricultural production.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112404DOI Listing
September 2021

Highly Fluorescent Cadmium Based Metal-Organic Frameworks for Rapid Detection of Antibiotic Residues, Fe and CrO Ions.

Inorg Chem 2021 Jun 7;60(12):9148-9156. Epub 2021 Jun 7.

School of Materials Science and Engineering, Changchun University of Science and Technology, Changchun 130022, People's Republic of China.

Here, two novel 3D Cd(II)-MOFs, [Cd··()·2DMF] and [(CdO)··] (denoted as and , = 9,10-bis(-benzimidazolyl)-anthracene, = 1,3,5-tris(4-carboxyphenyl) benzene, = 1,3,5-benzenetricarboxylic acid, CUST = Changchun University of Science and Technology), were synthesized by solvothermal conditions. Both and are 3D (3,8)-c topological nets with the same point symbol of {4}{4·6·8}. PXRD and TGA analyses prove that and have good structural stability and thermal stability. On the basis of the high fluorescence characteristics, the results of fluorescence sensing experiments show that and can be used as multifunctional chemical sensors to achieve rapid fluorescence quenching response to antibiotic residues, Fe and CrO ions at a much lower concentration. Furthermore, the possible mechanisms of fluorescence quenching in the sensing process were systematically studied by PXRD, UV-vis, fluorescence decay lifetime, and density functional theory.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01165DOI Listing
June 2021

Involvement of microRNA-155 in the mechanism of electroacupuncture treatment effects on experimental autoimmune encephalomyelitis.

Int Immunopharmacol 2021 Jun 3;97:107811. Epub 2021 Jun 3.

Department of Neurobiology, Harbin Medical University, No. 194 Xuefu Road, Harbin, Heilongjiang 150081, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang 150081, China. Electronic address:

Multiple sclerosis (MS) is a neurodegenerative and demyelinating autoimmune disease mediated by autoreactive T cells that affects the central nervous system (CNS). Electroacupuncture (EA) has emerged as an alternative or supplemental treatment for MS, but the mechanism by which EA may alleviate MS symptoms is unresolved. Here, we examined the effects of EA at the Zusanli (ST36) acupoint on mice with experimental autoimmune encephalomyelitis (EAE), the predominant animal model of MS. The effects of EA on EAE emergence, inflammatory cell levels, proinflammatory cytokines, and spinal cord pathology were examined. EA treatment attenuated the EAE clinical score and associated spinal cord demyelination, while reducing the presence of proinflammatory cytokines in mononuclear cells (MNCs), downregulating microRNA (miR)-155, and upregulating the opioid peptide precursor proopiomelanocortin (POMC) in the CNS. Experiments in which cultured neurons were transfected with a miR-155 mimic or a miR-155 inhibitor further showed that the direct modulation of miR-155 levels could regulate POMC levels in neurons. In conclusion, the alleviation of EAE by EA is characterized by reduced proportions of Th1/Th17 cells and increased proportions of Th2 cells, POMC upregulation, and miR-155 downregulation, while miR-155 itself can suppress POMC expression. These results, support the hypothesis that the effects of EA on EAE may involve the downregulation of miR-155.
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http://dx.doi.org/10.1016/j.intimp.2021.107811DOI Listing
June 2021

Genetically and pharmacologically limiting RyR2 open time prevents neuronal hyperactivity of hippocampal CA1 neurons in brain slices of 5xFAD mice.

Neurosci Lett 2021 Jul 4;758:136011. Epub 2021 Jun 4.

Libin Cardiovascular Institute, Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. Electronic address:

Neuronal hyperactivity is an early, common manifestation of Alzheimer's disease (AD), and is believed to drive AD progression. Neuronal hyperactivity in the form of baseline activity (or spontaneous Ca transients) has consistently been demonstrated in mouse models of AD using two-photon in vivo Ca imaging of cortical or hippocampal neurons in anesthetized animals. Notably, these AD-related spontaneous Ca transients were hardly detected in acute hippocampal slices, probably due to neuronal damage during brain slicing. To better preserve neuronal activity, we employed the N-methyl-D-glucamine (NMDG) protective brain slicing protocol. We performed confocal in vitro Ca imaging of hippocampal CA1 neurons in optimized hippocampal slices. Consistent with previous in vivo studies, our in vitro studies using optimized brain slices also showed that limiting the open duration of the ryanodine receptor 2 (RyR2) by the RyR2 mutation E4872Q or by the R-carvedilol enantiomer prevented and rescued neuronal hyperactivity of hippocampal CA1 neurons from 5xFAD mice. Thus, genetically and pharmacologically limiting RyR2 open time prevented and rescued AD-related neuronal hyperactivity in vitro in optimized brain slices in the absence of anesthetics' influence. Our data also suggest that the NMDG protective brain slicing preparation offers an alternative means to study neuronal hyperactivity of various cell types in different brain regions, especially in regions that are not readily accessible to two-photon in vivo Ca imaging.
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http://dx.doi.org/10.1016/j.neulet.2021.136011DOI Listing
July 2021

Natural discoidal lipoproteins with tiny modification for tumor extracellular dissociation in antitumor chemoimmunotherapy.

Biomaterials 2021 May 29;275:120859. Epub 2021 May 29.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China; NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, Nanjing, 210009, China. Electronic address:

Appealing cancer immunotherapy requires synchronous presentation of tumor antigens and immunoadjuvant. Herein, a "one-step" modification strategy is proposed to tinily remould endogenous discoidal high density lipoprotein (dHDL) for tumor-homing and site-specific chemoimmunotherapy. For molecular targeting therapy, lipophilic immunoadjuvant CpG oligodeoxynucleotides is conjugated to facilitate HDL-surface anchoring; and GC nucleotides provide enough reservoir for completion of doxorubicin (Dox) "sandwich". After administration, the tiny size (~30 nm) of disc nanodrug can maneuver deeply into tumors for receptor binding and in situ structural collapse. The intracellular concentrated CpG-Dox induce potent immunogenic cell death from burst Dox liberation at acidic pH. In turn, the released antigens and CpG motifs are simultaneously recognized by dendritic cells for antigen presentation and antitumor T cell responses. Combination chemoimmunotherapy with discoidal nanodrugs performed highest tumor weight inhibitory of 93.2% and extend the median survival time at a safe level. Collectively, this study suggests that the minimalist revolution of natural dHDL particulates may provide a biomimicry nanoplatform for site-specific amplified chemoimmunotherapy.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120859DOI Listing
May 2021

function in lipid biosynthesis is required for arbuscular mycorrhizal symbiosis in rice.

Mol Plant Microbe Interact 2021 Jun 2. Epub 2021 Jun 2.

Nanjing University, 12581, School of Life Sciences, Nanjing, Jiangsu, China;

Arbuscular mycorrhiza (AM) is a mutualistic symbiosis formed between most land plants and Glomeromycotina fungi. During the symbiosis, plants provide organic carbon to fungi in exchange for mineral nutrients. Previous legume studies showed that the () gene is necessary for transferring lipids from plants to AM fungi (AMF) and is also likely to play a 'signaling' role at the root surface. To further explore functions in other plant lineages, in this study, two rice () genes, and , were identified as orthologs of legume . Examining their expression patterns during symbiosis revealed that only was strongly upregulated upon AMF inoculation. CRISPR/Cas9 mutagenesis was then performed to obtain three mutant lines (, , and ). After inoculation by AMF or , all the mutant lines showed extremely low colonization rates and the rarely observed arbuscules were all defective, thus supporting a conserved 'nutritional' role of between monocot and dicot lineages. As for the 'signaling' role, although the hyphopodia numbers formed by both AMF on mutants were indeed reduced, their morphology showed no abnormality, with fungal hyphae invading roots successfully. Promoter activities further indicated was not expressed in epidermal cells below hyphopodia or outer cortical cells enclosing fungal hyphae, but expressed exclusively in cortical cells containing arbuscules. It therefore suggested an indirect role of rather than a direct involvement in determining the symbiosis signals at the root surface.
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http://dx.doi.org/10.1094/MPMI-04-21-0097-RDOI Listing
June 2021

High Q-factor with spoof-anapole mode excitation in metamaterials.

Opt Lett 2021 Jun;46(11):2630-2633

In this Letter, numerical and experimental studies for the spoof-anapole effect are presented. Different from the anapole modes, when electric and toroidal dipole intensities are minimized, the spoof-anapole effect can be generated. The spoof-anapole effect can reduce the radiation losses with a high $Q$-factor. The concept is valid in various frequency bands from microwave range for millimeter-sized objects to visible range for nanoparticles. The spoof-anapole modes are first experimentally realized in microwave metamaterials. Almost perfect spoof-anapole behavior is observed, which produces an extremely high $Q$-factor at the resonance frequency. The experimental results agree well with the analytical ones and pave way to excite the non-radiating electromagnetic sources.
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http://dx.doi.org/10.1364/OL.425389DOI Listing
June 2021

Characterization of Reveals Its Role in Carotenoid Biosynthesis in Chinese Kale.

Front Plant Sci 2021 14;12:662684. Epub 2021 May 14.

College of Horticulture, Sichuan Agricultural University, Chengdu, China.

Carotenoids are organic pigments that play an important role in both plant coloration and human health; they are a critical subject in molecular breeding due to growing demand for natural molecules in both food and medicine. In this study, we focus upon characterizing , the carotenoid isomerase gene before the branch of the carotenoid biosynthetic pathway, which is expressed in all organs and developmental stages of Chinese kale, and BoaCRTISO, which is located in the chloroplast. The expression of is induced by strong light, red and blue combined light, and gibberellic acid treatment, but it is suppressed by darkness and abscisic acid treatment. We obtained -silenced plants via virus-induced gene silencing technology, and the silence efficiencies ranged from 52 to 77%. The expressions of most carotenoid and chlorophyll biosynthetic genes in -silenced plants were downregulated, and the contents of carotenoids and chlorophyll were reduced. Meanwhile, -silenced plants exhibited phenotypes of yellowing leaves and inhibited growth. This functional characterization of provides insight for the biosynthesis and regulation of carotenoid in Chinese kale.
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http://dx.doi.org/10.3389/fpls.2021.662684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160315PMC
May 2021

Prediction of Re-positivity for Coronavirus Nucleic Acid Among COVID-19 Patients in the Recovery Phase.

Front Med (Lausanne) 2021 5;8:620727. Epub 2021 May 5.

Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, China.

Although the pathogenesis and treatment of coronavirus disease 2019 (COVID-19) have been gradually revealed, the risk for re-emergence of coronavirus nucleic acids in recovered patients remains poorly understood. Hence, this study evaluated the risk predictors associated with re-positivity for virus nucleic acid. Between February 1 and March 20, 2020, we retrospectively reviewed the clinical epidemiological data of 129 COVID-19 patients who were treated at Zhongxiang People's Hospital of Hubei Province in China. Subsequently, a risk prediction model for the re-positivity of virus nucleic acid was developed, and a receiver operating characteristic (ROC) curve was drawn for further validation. In this study, the rate of re-positivity for virus nucleic acid was 17.8% (23/129) where all re-positivity cases were asymptomatic. The median time interval from discharge to nucleic acid re-positivity to discharge after being cured again was 11.5 days (range: 7-23 days). Multivariate logistic regression analysis showed that leukocytopenia [odds ratio (OR) 7.316, 95% confidence interval (CI) 2.319-23.080, = 0.001], prealbumin < 150 mg/L (OR 4.199, 95% CI 1.461-12.071, = 0.008), and hyperpyrexia (body temperature >39°C, OR 4.643, 95% CI 1.426-15.117, = 0.011) were independent risk factors associated with re-positivity. The area under the ROC curve was 0.815 (95% CI, 0.729-0.902). COVID-19 patients with leukocytopenia, low prealbumin level, and hyperpyrexia are more likely to test positive for virus nucleic acid after discharge. Timely and effective treatment and appropriate extension of hospital stays and quarantine periods may be feasible strategies for managing such patients.
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http://dx.doi.org/10.3389/fmed.2021.620727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131547PMC
May 2021

Structural characterization of PaFkbA: A periplasmic chaperone from .

Comput Struct Biotechnol J 2021 25;19:2460-2467. Epub 2021 Apr 25.

Center of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China.

Bacterial Mip-like FK506-binding proteins (FKBPs) mostly exhibit peptidyl-prolyl-cis/-isomerase (PPIase) and chaperone activities. These activities are associated with various intracellular functions with diverse molecular mechanisms. Herein, we report the gene-encoded crystal structure of the PAO1's Mip-like protein PaFkbA. Biochemical characterization of PaFkbA demonstrated PaFkbA's chaperone activity for periplasmic protein MucD, a negative regulator of alginate biosynthesis. Furthermore, structural analysis of PaFkbA was used to describe the key features of PaFkbA chaperone activity. The outcomes of this analysis showed that the hinge region in the connecting helix of PaFbkA leads to the crucial conformational state transition for PaFkbA activity. Besides, the N-terminal domains participated in dimerization, and revealed its potential connection with FKBP domain and substrate binding. Mutagenesis and chaperone activity assay supported the theory that inter-domain motions are essential for PaFkbA function. These results provide biochemical and structural insights into the mechanism for FKBP's chaperone activity and establish a plausible correlation between PaFkbA and MucD.
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http://dx.doi.org/10.1016/j.csbj.2021.04.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113782PMC
April 2021

Mutation Screening of the Gene in a Large Chinese Cohort of Amyotrophic Lateral Sclerosis Patients.

Front Neurosci 2021 5;15:595775. Epub 2021 May 5.

Neurological Department of the First Medical Center, Chinese PLA General Hospital, Beijing, China.

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease involving the upper and lower motor neurons of the spinal cord, brainstem, and cerebral cortex. At least 30 genes have been implicated in familial ALS (fALS) and sporadic ALS (sALS). Kaneb et al. (2015) first carried out a large-scale sequencing study in ALS patients and identified two loss-of-function (LOF) variants in the gene. The LOF mutation-induced disruption of RNA metabolism through the haploinsufficiency mechanism is implicated in ALS pathogenesis. A total of 628 ALS patients and 522 individuals without neurodegenerative disorders were enrolled in this study to explore the gene contribution to ALS in the Chinese population. All 16 exons and the flanking intron of GLE1 were screened by Sanger sequencing. In total, we identified seven rare GLE1 coding variants, including one novel nonsense mutation and six rare missense mutations in 628 ALS patients. The frequency of GLE1 LOF mutations was 0.16% (1/628) among Chinese sALS patients, implying that it is an uncommon genetic determinant of ALS in Chinese patients. Additionally, the rare missense variants in the hCG1-binding domain of GLE1 impairing the distribution of the hGle1B isoform at the nuclear pore complex (NPC) region may be involved in the pathogenesis of ALS.
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http://dx.doi.org/10.3389/fnins.2021.595775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131544PMC
May 2021

RyR2 disease mutations at the C-terminal domain intersubunit interface alter closed-state stability and channel activation.

J Biol Chem 2021 May 20;297(1):100808. Epub 2021 May 20.

Libin Cardiovascular Institute, Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada. Electronic address:

Ryanodine receptors (RyRs) are ion channels that mediate the release of Ca from the sarcoplasmic reticulum/endoplasmic reticulum, mutations of which are implicated in a number of human diseases. The adjacent C-terminal domains (CTDs) of cardiac RyR (RyR2) interact with each other to form a ring-like tetrameric structure with the intersubunit interface undergoing dynamic changes during channel gating. This mobile CTD intersubunit interface harbors many disease-associated mutations. However, the mechanisms of action of these mutations and the role of CTD in channel function are not well understood. Here, we assessed the impact of CTD disease-associated mutations P4902S, P4902L, E4950K, and G4955E on Ca- and caffeine-mediated activation of RyR2. The G4955E mutation dramatically increased both the Ca-independent basal activity and Ca-dependent activation of [H]ryanodine binding to RyR2. The P4902S and E4950K mutations also increased Ca activation but had no effect on the basal activity of RyR2. All four disease mutations increased caffeine-mediated activation of RyR2 and reduced the threshold for activation and termination of spontaneous Ca release. G4955D dramatically increased the basal activity of RyR2, whereas G4955K mutation markedly suppressed channel activity. Similarly, substitution of P4902 with a negatively charged residue (P4902D), but not a positively charged residue (P4902K), also dramatically increased the basal activity of RyR2. These data suggest that electrostatic interactions are involved in stabilizing the CTD intersubunit interface and that the G4955E disease mutation disrupts this interface, and thus the stability of the closed state. Our studies shed new insights into the mechanisms of action of RyR2 CTD disease mutations.
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http://dx.doi.org/10.1016/j.jbc.2021.100808DOI Listing
May 2021

The dissection of R genes and locus Pc5.1 in Phytophthora capsici infection provides a novel view of disease resistance in peppers.

BMC Genomics 2021 May 21;22(1):372. Epub 2021 May 21.

College of Horticulture, Sichuan Agricultural University, Chengdu, 611130, China.

Background: Phytophthora capsici root rot (PRR) is a disastrous disease in peppers (Capsicum spp.) caused by soilborne oomycete with typical symptoms of necrosis and constriction at the basal stem and consequent plant wilting. Most studies on the QTL mapping of P. capsici resistance suggested a consensus broad-spectrum QTL on chromosome 5 named Pc.5.1 regardless of P. capsici isolates and resistant resources. In addition, all these reports proposed NBS-ARC domain genes as candidate genes controlling resistance.

Results: We screened out 10 PRR-resistant resources from 160 Capsicum germplasm and inspected the response of locus Pc.5.1 and NBS-ARC genes during P. capsici infection by comparing the root transcriptomes of resistant pepper 305R and susceptible pepper 372S. To dissect the structure of Pc.5.1, we anchored genetic markers onto pepper genomic sequence and made an extended Pc5.1 (Ext-Pc5.1) located at 8.35 Mb-38.13 Mb on chromosome 5 which covered all Pc5.1 reported in publications. A total of 571 NBS-ARC genes were mined from the genome of pepper CM334 and 34 genes were significantly affected by P. capsici infection in either 305R or 372S. Only 5 inducible NBS-ARC genes had LRR domains and none of them was positioned at Ext-Pc5.1. Ext-Pc5.1 did show strong response to P. capsici infection and there were a total of 44 differentially expressed genes (DEGs), but no candidate genes proposed by previous publications was included. Snakin-1 (SN1), a well-known antimicrobial peptide gene located at Pc5.1, was significantly decreased in 372S but not in 305R. Moreover, there was an impressive upregulation of sugar pathway genes in 305R, which was confirmed by metabolite analysis of roots. The biological processes of histone methylation, histone phosphorylation, DNA methylation, and nucleosome assembly were strongly activated in 305R but not in 372S, indicating an epigenetic-related defense mechanism.

Conclusions: Those NBS-ARC genes that were suggested to contribute to Pc5.1 in previous publications did not show any significant response in P. capsici infection and there were no significant differences of these genes in transcription levels between 305R and 372S. Other pathogen defense-related genes like SN1 might account for Pc5.1. Our study also proposed the important role of sugar and epigenetic regulation in the defense against P. capsici.
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http://dx.doi.org/10.1186/s12864-021-07705-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139160PMC
May 2021

Development of mesoporous silica-based nanoprobes for optical bioimaging applications.

Biomater Sci 2021 May;9(10):3603-3620

College of Chemistry & Chemical Engineering, Nanjing University, Nanjing, 210023, P.R. China.

A mesoporous silica nanoparticle (MSN)-based nanoplatform has attracted growing attention in the biomedical field due to the unique characteristics of MSNs including a high surface area, tunable pore sizes, colloidal stability, ease of functionalization, and desirable biocompatibility. Typically, MSNs are designed as nanocarriers for the incorporation of a variety of contrast agents for bioimaging, which can address the intrinsic drawbacks of contrast agents, including poor solubility in water, rapid photobleaching, and low stability. This review summarizes the recent advances in the field of MSN-based nanoprobes for fluorescence imaging and photoacoustic (PA) imaging applications. The approaches for the incorporation of contrast agents into MSN-based nanoplatforms including encapsulating contrast agents within MSNs, covalently conjugating contrast agents on the surface or pores of MSNs, physically absorbing contrast agents in the pores of MSNs, and doping contrast agents in the framework of MSNs are introduced. MSN-based nanoprobes for fluorescence imaging and PA imaging are discussed. The enhanced fluorescence imaging and PA imaging performances of MSN-based nanoprobes relative to the bare contrast agents are introduced and the underlying mechanisms are discussed in detail. Finally, current challenges and perspectives of MSN-based nanoprobes in the bioimaging field are discussed.
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http://dx.doi.org/10.1039/d1bm00204jDOI Listing
May 2021

MiR-518a-5p Targets GZMB to Extenuate Vascular Endothelial Cell Injury Induced by Hypoxia-Reoxygenation and Thereby Improves Myocardial Ischemia.

Int Heart J 2021 May 15;62(3):658-665. Epub 2021 May 15.

Department of Cardiovascular Surgery, The First Affiliated Hospital of Harbin Medical University.

To probe the function of miR-518a-5p/Granzyme B (GZMB) in hypoxia/reoxygenation (H/R) -induced vascular endothelial cell injury.The key genes of myocardial infarction were screened by bioinformatic methods. The upstream micro RNAs (miRNAs) of GZMB were predicted by TargetScan. The binding of miR-518a-5p to GZMB was verified with luciferase reporter assay. The H/R model was constructed with human vascular endothelial cell (HUVEC) in vitro. Cell Counting Kit-8 (CCK8) assay was performed to detect cell proliferation. Western blot was utilized to evaluate the levels of indicated proteins.GZMB was up-regulated in patients with myocardial infarction and identified as the key gene by the bioinformatics analysis. Then the prediction from TargetScan indicated that miR-518a-5p, which is down-regulated in myocardial infarction patients, might be the potential upstream miRNA for GZMB. The following experiments verified that miR-518a-5p could bind to the 3'UTR of GZMB and negatively modulates GZMB expression. More importantly, the miR-518a-5p mimic enhanced cell proliferation and repressed apoptosis of H/R-injured HUVEC cells by inhibiting GZMB expression.We proved that miR-518a-5p could partly attenuate H/R-induced HUVEC cell injury by targeting GZMB, and perhaps the miR-518a-5p/GZMB axis could be potential therapeutic targets for myocardial infarction.
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http://dx.doi.org/10.1536/ihj.20-619DOI Listing
May 2021

METTL3/METTL14 Transactivation and mA-Dependent TGF-β1 Translation in Activated Kupffer Cells.

Cell Mol Gastroenterol Hepatol 2021 May 13. Epub 2021 May 13.

MOE Joint International Research Laboratory of Animal Health & Food Safety, Nanjing Agricultural University, Nanjing, Jiangsu, P. R. China; Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, P. R. China. Electronic address:

Background And Aims: Transforming growth factor β1 (TGF-β1) secreted from activated Kupffer cells (KCs) promotes the progression of nonalcoholic steatohepatitis (NASH) to liver fibrosis. N6-methyladenosine (mA) RNA modification participates in various cell stress responses, yet it remains unknown whether it plays a role in TGF-β1 upregulation in activated KCs.

Methods: Western blot, dot blot, and liquid chromatography with tandem mass spectrometry were used to determine the expression of mA methyltransferase, METTL3, and METTL14, as well as global mA modification. RNA-sequencing and mA-seq were employed to screen differentially expressed genes and responsive mA peaks. Nuclear factor κB (NF-κB)-mediated METTL3/METTL14 transactivation were validated with chromatin immunoprecipitation polymerase chain reaction and dual-luciferase reporter system, and the role of mA in TGF-β1 upregulation was further verified in METTL3/METTL14-deficient KCs and myeloid lineage cell-specific METTL14 knockout mice.

Results: Serum lipopolysaccharide (LPS) concentration is increased in high-fat diet-induced NASH rats. TGF-β1 upregulation is closely associated with METTL3/METTL14 upregulation and global mA hypermethylation, in both NASH rat liver and LPS-activated KCs. LPS-responsive mA peaks are identified on the 5' untranslated region (UTR) of TGF-β1 messenger RNA (mRNA). NF-κB directly transactivates METTL3 and METTL14 genes. LPS-stimulated TGF-β1 expression is abolished in METTL3/METTL14-deficient KCs and myeloid lineage cell-specific METTL14 knockout mice. Mutation of mA sites on the 5'UTR of TGF-β1 mRNA blocks LPS-induced increase of luciferase reporter activity.

Conclusions: NF-κB acts as transcription factor to transactivate METTL3/METTL14 genes upon LPS challenge, leading to global RNA mA hypermethylation. Increased mA on the 5'UTR of TGF-β1 mRNA results in mA-dependent translation of TGF-β1 mRNA in a cap-independent manner. We identify a novel role of mA modification in TGF-β1 upregulation, which helps to shed light on the molecular mechanism of NASH progression.
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http://dx.doi.org/10.1016/j.jcmgh.2021.05.007DOI Listing
May 2021

High-performance work systems, multiple commitments, and knowledge exchange and combination among Chinese public hospital nurses.

Nurs Open 2021 May 14. Epub 2021 May 14.

School of Economics and Management, Beijing University of Chemical Technology, Beijing, China.

Aim: This research explores and examines the differentiated mediation roles of multi-foci commitment in the relationship between HPWS and knowledge exchange and combination among Chinese hospital nurses.

Design: This study employs a quantitative research approach and survey design.

Methods: Individual-level time-lagged data were collected from 845 nurses in public hospitals in China using online questionnaires. Aside from personal information, the items in the questionnaires were adopted from mature scales in previous research.

Results: The results of multiple regression analysis demonstrate that nurses' professional and affective commitments partially mediate the relationship between HPWS and KEC. Nurses' continuance commitment does not play a mediation role in HPWS-KEC relationship, although HPWS positively influences nurse continuance commitment, which then weakly and positively impacts KEC.
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http://dx.doi.org/10.1002/nop2.921DOI Listing
May 2021

Correction to: A birth population-based survey of preterm morbidity and mortality by gestational age.

BMC Pregnancy Childbirth 2021 May 12;21(1):373. Epub 2021 May 12.

The NCH Key Laboratory of Neonatal Diseases, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, 201102, China.

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http://dx.doi.org/10.1186/s12884-021-03841-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117499PMC
May 2021

Occurrence, latitudinal gradient and potential sources of perchlorate in the atmosphere across the hemispheres (31°N to 80°S).

Environ Int 2021 May 8;156:106611. Epub 2021 May 8.

MNR Key Laboratory for Polar Science, Polar Research Institute of China, Shanghai 200136, China.

Perchlorate (ClO) is harmful to human health, and knowledge on the levels and sources of natural ClO in different environments remains rather limited. Here, we investigate ClO in aerosol samples collected along a cross-hemisphere ship cruise between China and Antarctica and on a traverse between coastal East Antarctica and the ice sheet summit (Dome Argus). Perchlorate concentrations range from a few to a few hundred pg m. A clear latitudinal trend is found, with elevated ClO concentrations near populated areas and in the southern mid-high latitudes. Spatial patterns of atmospheric ClO over oceans near the landmasses support that terrestrial ClO is not transported efficiently over long distances. In the southern mid-latitudes, higher ClO concentrations in March than in November-December may be caused by significant stratospheric inputs in March. Perchlorate concentrations appear to be higher in the warm half than in the cold half of the year in the southern high latitudes, suggesting seasonal difference in main atmospheric sources. ClO may be formed in the reactions between chlorine free radical (Cl·) and ozone (O) in the stratosphere when Antarctic ozone hole occurs during September-October. And the stratosphere-produced ClO is moved to the boundary layer in several months and may be responsible for the high ClO concentrations in the warm half of the year. Perchlorate produced by photochemical reactions between O and Cl· in the Antarctic stratosphere is likely responsible for the higher ClO concentrations in Antarctica than in Arctic.
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http://dx.doi.org/10.1016/j.envint.2021.106611DOI Listing
May 2021

Comparison of Survival of Preterm Newborn Rabbits at 25-28 Days of Gestation with Perinatal Therapies at Birth Transition.

J Appl Physiol (1985) 2021 May 6. Epub 2021 May 6.

Department of Pediatrics and Neonatology, Children's Hospital of Fudan University, China.

Background Eligibility of ventilated preterm rabbit model to investigate extreme pulmonary immaturity at birth transition is unknown. By extending this model to early saccular stage of fetal lung development, we evaluated efficacy in survival, lung maturation and underlying mechanisms of contemporary perinatal therapies.

Methods: Pregnant New Zealand White rabbit does were given dexamethasone (DEX), or sham injection as control (NDEX), 48 and 24 h before delivery at gestational age (GA) of 25-28 days. At birth, newborn rabbits were anesthetized and randomly allocated to four groups receiving either surfactant or non-surfactant for both DEX and NDEX, and mechanically ventilated within low tidal volumes.

Results: Ranges of time to maintain survival rate ≥ 50% in GA 25-28 days were 59-136, 138-259, 173-288, and 437 to >600 min, respectively, each across the four groups. The benefits of DEX and/or surfactant for survival were more obvious in GA 25-26 days, as judged by improved lung mechanics, lower lung injury scores, higher lung surfactant phospholipid pools and surfactant protein mRNA expression, with DEX-surfactant combination being the most optimal for the outcome. In contrast, those of GA 27-28 days had variable but meaningful responses to the treatment. Cox regression analysis revealed GA, DEX and surfactant being independently protective factors while pneumothorax a risk factor.

Conclusion: The extremely preterm rabbits at GA 25-26 days markedly responded to the perinatal therapies for longer survival, lung maturation and injury alleviation, and were relevant for study of preterm birth transition-associated morbidities and underlying mechanisms.
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http://dx.doi.org/10.1152/japplphysiol.00027.2021DOI Listing
May 2021

HSP60 in cancer: a promising biomarker for diagnosis and a potentially useful target for treatment.

J Drug Target 2021 May 3:1-15. Epub 2021 May 3.

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, PR China.

Heat shock proteins (HSPs), most of which are molecular chaperones, are highly conserved proteins produced by cells under physiological stress or pathological conditions. HSP60 (57-69 kDa) can promote or inhibit cell apoptosis through different mechanisms, and its abnormal expression is also related to tumour cell metastasis and drug resistance. In recent years, HSP60 has received increasing attention in the field of cancer research due to its potential as a diagnostic and prognostic biomarker or therapeutic target. However, in different types of cancer, the specific mechanisms of abnormally expressed HSP60 in tumour carcinogenesis and drug resistance are complicated and still require further study. In this article, we comprehensively review the regulative mechanisms of HSP60 on apoptosis, its applications as a cancer diagnostic biomarker and a therapeutic target, evidence of involvement in tumour resistance and the applications of exosomal HSP60 in liquid biopsy. By evaluating the current findings of HSP60 in cancer research, we highlight some core issues that need to be addressed for the use of HSP60 as a diagnostic or prognostic biomarker and therapeutic target in certain types of cancer.
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http://dx.doi.org/10.1080/1061186X.2021.1920025DOI Listing
May 2021

NAD(P)HX epimerase downregulation promotes tumor progression through ROS/HIF-1α signaling in hepatocellular carcinoma.

Cancer Sci 2021 May 1. Epub 2021 May 1.

Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.

Reactive oxygen species (ROS) derived from aberrant tumor metabolism could contribute to tumor invasion and metastasis. NAD(P)HX Epimerase (NAXE), an epimerase that allows the repair of damaged forms of antioxidant NADPH, is a potential cellular ROS scavenger and its role in tumor development is still elusive. Here, we found that NAXE is significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. NAXE downregulation is associated with poor clinicopathological characteristics and is an independent risk factor for overall and disease-free survival of HCC patients after liver resection. In addition, low NAXE expression could identify worse prognosis of HCC patients before vascular invasion or in early stages of disease. In particularly, low NAXE expression in HCC is markedly associated with microvascular invasion (MVI) and its combination with MVI predicts poorer prognosis of HCC patients after liver resection. Furthermore, in vitro and in vivo experiments both showed that knockdown of NAXE expression in HCC cells promoted migration, invasion, and metastasis by inducing epithelial-mesenchymal transition (EMT), whereas NAXE overexpression causes the opposite effects. Mechanistically, low NAXE expression reduced NADPH levels and further caused ROS level increase and hypoxia-inducible factor-1α (HIF-1α) activation, thereby promoting invasion and metastasis of HCC by facilitating EMT. What is more, the tumor-promoting effect of NAXE knockdown in HCC xenograft can be abolished by giving mice N-acetyl-l-cysteine (NAC) in drinking water. Taken together, our findings uncovered a tumor suppressor role for NAXE in HCC by scavenging excessive ROS and inhibiting tumor-promoting signaling pathways, suggesting a new strategy for HCC therapy by targeting redox signaling.
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http://dx.doi.org/10.1111/cas.14925DOI Listing
May 2021