Publications by authors named "Li Zha"

36 Publications

Association of Gut Microbiota during Early Pregnancy with Risk of Incident Gestational Diabetes Mellitus.

J Clin Endocrinol Metab 2021 May 20. Epub 2021 May 20.

Key Laboratory of Environment & Health ( Huazhong University of Science and Technology), Ministry of Education.

Aims: We aimed to assess the association between gut bacterial biomarkers during early pregnancy and subsequent risk of gestational diabetes mellitus (GDM) in Chinese pregnant women.

Methods: Within the Tongji-Shuangliu Birth Cohort study, we conducted a nested case-control study among 201 incident GDM cases and 201 matched controls. Fecal samples were collected during early pregnancy (at 6-15 weeks), and GDM was diagnosed at 24-28 weeks of pregnancy. Community DNA isolated from fecal samples and V3-V4 region of 16S rRNA gene amplicon libraries were sequenced.

Results: In GDM cases versus controls, Rothia, Actinomyces, Bifidobacterium, Adlercreutzia, and Coriobacteriaceae, and Lachnospiraceae spp. were significantly reduced, while Enterobacteriaceae, Ruminococcaceae spp. and Veillonellaceae were over-represented. In addition, the abundance of Staphylococcus relative to Clostridium, Roseburia and Coriobacteriaceae as reference microorganisms were positively correlated with fasting blood glucose, 1-h and 2-h postprandial glucose levels. Adding microbial taxa to the base GDM prediction model with conventional risk factors increased the C-statistic significantly (P<0.001) from 0.69 to 0.75.

Conclusions: Gut microbiota during early pregnancy was associated with subsequent risk of GDM. Several beneficial and commensal gut microorganisms showed inverse relations with incident GDM, while opportunistic pathogenic members were related to higher risk of incident GDM and positively correlated with glucose levels on OGTT.
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http://dx.doi.org/10.1210/clinem/dgab346DOI Listing
May 2021

Ivabradine protects rats against myocardial infarction through reinforcing autophagy via inhibiting PI3K/AKT/mTOR/p70S6K pathway.

Bioengineered 2021 Dec;12(1):1826-1837

Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.

Ivabradine (Iva), a heart rate reducing agent that specifically inhibits the pacemaker ionic current, has been demonstrated to be cardioprotective in many cardiovascular diseases. Autophagy is an evolutionarily conserved metabolic process that regulates cardiac homeostasis. This study is aimed to explore whether autophagy is functionally involved in the cardioprotective effect of Iva in a rat model of myocardial infarction (MI). We observed that Iva treatment (po, 10 mg/kg/day) showed significant recovery on the hemodynamics parameters in MI rats, including left ventricular systolic pressure, left ventricular end diastolic pressure, and maximal ascending/descending rate of left ventricular pressure. Also, Iva treatment dramatically decreased infarct size, inhibited myocardial apoptosis, and reduced the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in MI rats. Moreover, Iva treatment enhanced autophagy and inhibited PI3K/AKT/mTOR/p70S6K pathway in MI rats. Simultaneously, we observed that autophagy enhancer rapamycin (ip, 10 mg/kg/day) showed similar cardioprotective effects with Iva. Furthermore, we observed that addition of autophagy inhibitor 3-methyladenine (ip, 10 mg/kg/day) counteracted the therapeutic effect of Iva, addressing that Iva attenuated post-MI cardiac injury by enhancing autophagy. In summary, these findings demonstrated that Iva attenuated MI in rats by enhancing autophagy, and PI3K/AKT/mTOR/p70S6K pathway might be involved in the process. Autophagy activation by Iva may be a potential therapeutic strategy for the treatment of MI.
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http://dx.doi.org/10.1080/21655979.2021.1925008DOI Listing
December 2021

Blockade of AIM2 inflammasome or α1-AR ameliorates IL-1β release and macrophage-mediated immunosuppression induced by CAR-T treatment.

J Immunother Cancer 2021 Jan;9(1)

Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China

Background: Interleukin (IL) 1 released from monocytes/macrophages is one of the critical determinants in mediating the adverse events of chimeric antigen receptor T cell (CAR-T) therapy, including cytokine release syndrome and neurotoxicity. However, the molecular mechanisms of IL-1 production during CAR-T therapy remain unknown.

Methods: The roles of AIM2 and α1-adrenergic receptor (α1-AR) in CAR-T treatment-induced IL-1β release were evaluated by gene silencing, agonist or antagonist treatment. The phenotype switch of macrophages in response to CAR-T treatment was analyzed concerning cytotoxicity of CAR-T cells and proliferation of activated T cells.

Results: This study provided the experimental evidence that CAR-T treatment-induced activation of AIM2 inflammasome of macrophages resulted in the release of bioactive IL-1β. CAR-T treatment-induced α1-AR-mediated adrenergic signaling augmented the priming of AIM2 inflammasome by enhancing IL-1β mRNA and AIM2 expression. Meanwhile, tumor cell DNA release triggered by CAR-T treatment potentiated the activation of AIM2 inflammasome in macrophages. Interestingly, an apparent phenotypic switch in macrophages occurred after interacting with CAR-T/tumor cells, which greatly inhibited the cytotoxicity of CAR-T cells and proliferation of activated T cells through upregulation of programmed cell death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase (IDO) in the macrophages. Blockade of AIM2 inflammasome or α1-AR reversed the upregulation of PD-L1 and IDO and the phenotypic switch of the macrophages.

Conclusion: Our study implicates that CAR-T therapy combined with the blockade of AIM2 inflammasome or α1-AR may relieve IL-1β-related toxic side effects of CAR-T therapy and ensure antitumor effects of the treatment.
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http://dx.doi.org/10.1136/jitc-2020-001466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797290PMC
January 2021

β2-AR activation promotes cleavage and nuclear translocation of Her2 and metastatic potential of cancer cells.

Cancer Sci 2020 Dec 27;111(12):4417-4428. Epub 2020 Oct 27.

Cancer Institute, Xuzhou Medical University, Xuzhou, China.

Prolonged hypersecretion of catecholamine induced by chronic stress may correlate with malignant progression of cancer. β2-adrenergic receptor (β2-AR) overexpressed in certain cancer cells may translate the signals from neuroendocrine system to malignant signals by interacting with oncoproteins, such as Her2. In the present study, we demonstrate that catecholamine stimulation activates the expression and proteolytic activity of ADAM10 by modulating the expression of miR-199a-5p and SIRT1 and also confirm that catecholamine induction triggers the activities of γ-secretase, leading to shedding of Her2 extracellular domain (ECD) by ADAM10 and subsequent intramembranous cleavage of Her2 intracellular domain (ICD) by presenilin-dependent γ-secretase, nuclear translocation of Her2 ICD, and enhanced transcription of tumor metastasis-associated gene COX-2. Chronic stimulation of catecholamine strongly promotes the invasive activities of cancer cells in vitro and spontaneous tumor lung metastasis in mice. Furthermore, nuclear localization of Her2 was significantly correlated with overexpression of β2-AR in human breast cancer tissues, indicating that catecholamine-induced β2-AR activation plays decisive roles in tumor metastasis. Our data also reveal that an unknown mechanism by which the regulated intramembrane proteolysis (RIP) initiated by β2-AR-mediated signaling controls a novel Her2-mediated signaling transduction.
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http://dx.doi.org/10.1111/cas.14676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734010PMC
December 2020

Author Correction: Clinical Validation of Targeted and Untargeted Metabolomics Testing for Genetic Disorders: A 3 Year Comparative Study.

Sci Rep 2020 Jul 7;10(1):11160. Epub 2020 Jul 7.

Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-68532-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341886PMC
July 2020

Clinical Validation of Targeted and Untargeted Metabolomics Testing for Genetic Disorders: A 3 Year Comparative Study.

Sci Rep 2020 06 10;10(1):9382. Epub 2020 Jun 10.

Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Global untargeted metabolomics (GUM) has entered clinical diagnostics for genetic disorders. We compared the clinical utility of GUM with traditional targeted metabolomics (TM) as a screening tool in patients with established genetic disorders and determined the scope of GUM as a discovery tool in patients with no diagnosis under investigation. We compared TM and GUM data in 226 patients. The first cohort (n = 87) included patients with confirmed inborn errors of metabolism (IEM) and genetic syndromes; the second cohort (n = 139) included patients without diagnosis who were undergoing evaluation for a genetic disorder. In patients with known disorders (n = 87), GUM performed with a sensitivity of 86% (95% CI: 78-91) compared with TM for the detection of 51 diagnostic metabolites. The diagnostic yield of GUM in patients under evaluation with no established diagnosis (n = 139) was 0.7%. GUM successfully detected the majority of diagnostic compounds associated with known IEMs. The diagnostic yield of both targeted and untargeted metabolomics studies is low when assessing patients with non-specific, neurological phenotypes. GUM shows promise as a validation tool for variants of unknown significance in candidate genes in patients with non-specific phenotypes.
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http://dx.doi.org/10.1038/s41598-020-66401-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287104PMC
June 2020

CRISPR screen in mechanism and target discovery for cancer immunotherapy.

Biochim Biophys Acta Rev Cancer 2020 08 13;1874(1):188378. Epub 2020 May 13.

Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou 221000, Jiangsu, China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou 221000, Jiangsu, China. Electronic address:

CRISPR/Cas-based genetic perturbation screens have emerged as powerful tools for large-scale identification of new targets for cancer immunotherapy. Various strategies of CRISPR screen have been used for immune-oncology (IO) target discovery. The genomic sequences targeted by CRISPR/Cas system range from coding sequences to non-coding RNA/DNA, including miRNAs, LncRNAs, circRNAs, promoters, and enhancers, which may be potential targets for future pharmacological and therapeutic interventions. Rapid progresses have been witnessed in finding novel targets for enhancing tumor antigen presentation, sensitizing of tumor cells to immune-mediated cytotoxicity, and reinvigorating tumor-specific T cells by using CRISPR technologies. In combination with other strategies, the detailed characteristics of the targets for immunotherapy have been obtained by CRISPR screen. In this review, we present an overview of recent progresses in the development of CRISPR-based screens for IO target identification and discuss the challenges and possible solutions in this rapidly growing field.
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http://dx.doi.org/10.1016/j.bbcan.2020.188378DOI Listing
August 2020

Consolidation of vitamin A and E methods onto a multiplexing liquid chromatography tandem mass spectrometry platform simplifies laboratory workflow.

Clin Chim Acta 2020 Jun 19;505:31-33. Epub 2020 Feb 19.

Boston Children's Hospital, Department of Laboratory Medicine, 300 Longwood Avenue, Boston, MA, USA. Electronic address:

Background: Vitamin A and E are routinely monitored to assess nutritional status. The most commonly used approach for their measurement involves laborious liquid-liquid extraction followed by high-performance liquid chromatography (HPLC) analysis on dedicated instrumentation. We describe a simple, rapid protocol for measurement of vitamin A and E and their integration into an existing online sample preparation liquid chromatography tandem mass spectrometry (SPLC-MS/MS) workflow.

Methods: We performed a method comparison between the SPLC-MS/MS and HPLC methods for vitamin A and E by measuring patient specimens across the concentration range 11-81 µg/dL for vitamin A and 1-18 mg/L for vitamin E. The analysis times on each platform were also compared.

Results: SPLC-MS/MS and HPLC methods were comparable with regards to analytical performance; mean bias across the measured range was 2.54% (95% CL: -11.56-16.64%) for vitamin A and -2.04% (95% CL: -18.20-14.12%) for vitamin E. Total analysis times were 7 min and 15 min for SPLC-MS/MS and HPLC respectively.

Conclusions: The development of a simplified sample preparation protocol and the use of multiplexing SPLC-MS/MS have reduced sample analysis times for vitamin A and E. This method has also optimized clinical workflow through consolidation of previously independent benches.
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http://dx.doi.org/10.1016/j.cca.2020.02.020DOI Listing
June 2020

Atomically thin two-dimensional ZnSe/ZnSe(ea) van der Waals nanojunctions for synergistically enhanced visible light photocatalytic H evolution.

Nanoscale 2019 Oct;11(38):17718-17724

Engineering Research Center of Nano-Geo Materials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, 388 Lumo Road, Wuhan, 430074, China.

Two-dimensional (2D) photocatalysts have been widely studied due to their short charge carrier migration pathways and tunable electronic structures. Herein, a facile one-pot solvothermal process with ethylamine (ea) constructs a novel 2D nanojunction based on ZnSe. The ea molecules coordinate with Zn2+ to form 2D ZnSe(ea)x, where the consequent 2D ZnSe grows in an epitaxial way resulting in the self-assembled 2D/2D ZnSe/ZnSe(ea)x nanojunctions driven by van der Waals (VDW) force, which largely extend the absorption range. The atomic thickness of the 2D structure offers a short charge migration pathway, low electric resistance and rich active sites for the surface reaction of photocatalysis. All the above favorable factors work synergistically to reach a superior hydrogen evolution of 2875 μmol g-1 h-1 under visible light irradiation (≥420 nm) and a notable quantum yield of 64.5% at 450 nm, which are among the highest recorded values of non-noble metal photocatalysts.
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http://dx.doi.org/10.1039/c9nr06305fDOI Listing
October 2019

Reactivity of an Unusual Amidase May Explain Colibactin's DNA Cross-Linking Activity.

J Am Chem Soc 2019 07 11;141(29):11489-11496. Epub 2019 Jul 11.

Department of Chemistry and Chemical Biology , Harvard University , 12 Oxford Street , Cambridge , Massachusetts 02138 , United States.

Certain commensal and pathogenic bacteria produce colibactin, a small-molecule genotoxin that causes interstrand cross-links in host cell DNA. Although colibactin alkylates DNA, the molecular basis for cross-link formation is unclear. Here, we report that the colibactin biosynthetic enzyme ClbL is an amide bond-forming enzyme that links aminoketone and β-keto thioester substrates in vitro and in vivo. The substrate specificity of ClbL strongly supports a role for this enzyme in terminating the colibactin NRPS-PKS assembly line and incorporating two electrophilic cyclopropane warheads into the final natural product scaffold. This proposed transformation was supported by the detection of a colibactin-derived cross-linked DNA adduct. Overall, this work provides a biosynthetic explanation for colibactin's DNA cross-linking activity and paves the way for further study of its chemical structure and biological roles.
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http://dx.doi.org/10.1021/jacs.9b02453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728428PMC
July 2019

The genome of cultivated peanut provides insight into legume karyotypes, polyploid evolution and crop domestication.

Nat Genet 2019 05 1;51(5):865-876. Epub 2019 May 1.

Center of Excellence in Genomics & Systems Biology, International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), Hyderabad, India.

High oil and protein content make tetraploid peanut a leading oil and food legume. Here we report a high-quality peanut genome sequence, comprising 2.54 Gb with 20 pseudomolecules and 83,709 protein-coding gene models. We characterize gene functional groups implicated in seed size evolution, seed oil content, disease resistance and symbiotic nitrogen fixation. The peanut B subgenome has more genes and general expression dominance, temporally associated with long-terminal-repeat expansion in the A subgenome that also raises questions about the A-genome progenitor. The polyploid genome provided insights into the evolution of Arachis hypogaea and other legume chromosomes. Resequencing of 52 accessions suggests that independent domestications formed peanut ecotypes. Whereas 0.42-0.47 million years ago (Ma) polyploidy constrained genetic variation, the peanut genome sequence aids mapping and candidate-gene discovery for traits such as seed size and color, foliar disease resistance and others, also providing a cornerstone for functional genomics and peanut improvement.
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http://dx.doi.org/10.1038/s41588-019-0402-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188672PMC
May 2019

Circularly polarized light detection using chiral hybrid perovskite.

Nat Commun 2019 04 26;10(1):1927. Epub 2019 Apr 26.

Sargent joint research center, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, P. R. China.

Circularly polarized light (CPL) detection is required in various fields such as drug screening, security surveillance and quantum optics. Conventionally, CPL photodetector needs the installation of optical elements, imposing difficulties for integrated and flexible devices. The established CPL detectors without optical elements rely on chiral organic semiconductor and metal metamaterials, but they suffer from extremely low responsivity. Organic-inorganic hybrid materials combine CPL-sensitive absorption induced by chiral organics and efficient charge transport of inorganic frameworks, providing an option for direct CPL detection. Here we report the CPL detector using chiral organic-inorganic hybrid perovskites, and obtain a device with responsivity of 797 mA W, detectivity of 7.1 × 10 Jones, 3-dB frequency of 150 Hz and one-month stability, a competitive combined feature for circularly polarized light detection. Thanks to the solution processing, we further demonstrate flexible devices on polyethylene terephthalate substrate with comparable performance.
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http://dx.doi.org/10.1038/s41467-019-09942-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486588PMC
April 2019

Aqueous Synthesis of Lead Halide Perovskite Nanocrystals with High Water Stability and Bright Photoluminescence.

ACS Appl Mater Interfaces 2018 Dec 7;10(50):43915-43922. Epub 2018 Dec 7.

Lead halide perovskite nanocrystals (NCs) have attracted intense attention because of their excellent optoelectronic properties. The ionic nature of halide perovskites makes them highly vulnerable to water. Encapsulation of perovskite NCs with inorganic or organic materials has been reported to enhance their stability; however, they often suffer from large aggregation size, low water solubility, and difficulty for further surface functionalization. Here, we report a facile aqueous process to synthesize water-soluble CsPbBr/CsPbBr NCs with the assistance of a fluorocarbon agent (FCA), which features a novel mechanism of the perovskite crystallization at the oil/water interface and direct perovskite NCs/FCA self-assembly in an aqueous environment. The products exhibit a high absolute photoluminescence quantum yield (PLQY) of ∼80% in water with the PL lasting for weeks. Through successive ionic layer adsorption and reaction, BaSO was further applied to encapsulate the NCs, which greatly enhanced their stability in phosphate-buffered saline solutions. The high stability in water and saline solution, high PLQY, and tunable emission wavelength, together with the successful demonstration of brain tissue labeling and PL under X-ray excitation, make our perovskite NCs a promising choice for X-ray fluorescent biolabels.
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http://dx.doi.org/10.1021/acsami.8b16471DOI Listing
December 2018

Arginine does not rescue p.Q188R mutation deleterious effect in classic galactosemia.

Orphanet J Rare Dis 2018 11 26;13(1):212. Epub 2018 Nov 26.

Department of Clinical Genetics, Maastricht University Medical Center +, Maastricht, The Netherlands.

Background: Classic galactosemia is a rare genetic metabolic disease with an unmet treatment need. Current standard of care fails to prevent chronically-debilitating brain and gonadal complications. Many mutations in the GALT gene responsible for classic galactosemia have been described to give rise to variants with conformational abnormalities. This pathogenic mechanism is highly amenable to a therapeutic strategy based on chemical/pharmacological chaperones. Arginine, a chemical chaperone, has shown beneficial effect in other inherited metabolic disorders, as well as in a prokaryotic model of classic galactosemia. The p.Q188R mutation presents a high prevalence in the Caucasian population, making it a very clinically relevant mutation. This mutation gives rise to a protein with lower conformational stability and lower catalytic activity. The aim of this study is to assess the potential therapeutic role of arginine for this mutation.

Methods: Arginine aspartate administration to four patients with the p.Q188R/p.Q188R mutation, in vitro studies with three fibroblast cell lines derived from classic galactosemia patients as well as recombinant protein experiments were used to evaluate the effect of arginine in galactose metabolism. This study has been registered at https://clinicaltrials.gov (NCT03580122) on 09 July 2018. Retrospectively registered.

Results: Following a month of arginine administration, patients did not show a significant improvement of whole-body galactose oxidative capacity (p = 0.22), erythrocyte GALT activity (p = 0.87), urinary galactose (p = 0.52) and urinary galactitol levels (p = 0.41). Patients' fibroblasts exposed to arginine did not show changes in GALT activity. Thermal shift analysis of recombinant p.Q188R GALT protein in the presence of arginine did not exhibit a positive effect.

Conclusions: This short pilot study in four patients homozygous for the p.Q188R/p.Q188R mutation reveals that arginine has no potential therapeutic role for galactosemia patients homozygous for the p.Q188R mutation.
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http://dx.doi.org/10.1186/s13023-018-0954-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260575PMC
November 2018

Adjacent skin rotation flap for large defect in primary breast tumor.

J Surg Oncol 2018 Dec 7;118(7):1199-1204. Epub 2018 Oct 7.

Department of Breast Surgery, Hubei Cancer Hospital, Wuhan, China.

Backgrounds: Surgical resection of large primary breast tumor often results in large chest wall defects. The purpose of this study is to evaluate the feasibility of using adjacent skin rotation (ASR) flap in patients with giant primary breast tumor.

Methods: A total of 26 giant primary breast tumor patients treated with ASR flap were included in this study. The postoperative conditions, including operating time, blood loss, length of hospital stay, and clinical complications were observed. Meanwhile, the information on 17 breast tumor patients treated with transverse rectus abdominis myocutaneous (TRAM) flap were collected and assigned to a control group.

Results: The mean defect size after mastectomy was 16.7 × 13.4 cm, while the median follow-up period was 13 months after surgery. A total of 15.4% patients had developed with local complications, and one of them had more than one complication. When comparing the postoperative outcomes, statistically significant differences were found between the two groups with respect to operating time, blood loss, and length of hospital stay (P < 0.001).

Conclusions: ASR flap is a reliable technique for immediate reconstruction of massive chest wall defects in patients with giant primary breast tumor.
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http://dx.doi.org/10.1002/jso.25240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687872PMC
December 2018

TNF-α contributes to postmenopausal osteoporosis by synergistically promoting RANKL-induced osteoclast formation.

Biomed Pharmacother 2018 Jun 22;102:369-374. Epub 2018 Mar 22.

Department of Orthopaedics, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiao Tong University Medical School, Chengdu, Sichuan 610031, China. Electronic address:

Previous studies showed that inflammatory cytokines promote osteoclast formation, characterized by the function of bone resorption. However, it remains unclear whether inflammatory factors contribute to osteoporosis syndrome in postmenopausal women. Here, we found that postmenopausal women with osteoporosis (PO) had increased levels of TNF-α, compared with those without osteoporosis. TNF-α is highly correlated with the RANK and estrogen levels in PO patients. in vitro, TNF-α synergistically promotes RANKL-induced osteoclast formation by activation of NF-κB and PI3K/Akt signaling. Moreover, inhibition of PI3K/Akt totally blocked the synergistic effects of TNF-α on NF-κB activation as well as osteoclast formation. Together, these results demonstrate that TNF-α synergistically promotes RANKL-induced osteoclasts formation through activation of PI3K/Akt signaling, which ultimately contributes to osteoporosis syndrome in postmenopausal women.
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http://dx.doi.org/10.1016/j.biopha.2018.03.080DOI Listing
June 2018

Colibactin assembly line enzymes use S-adenosylmethionine to build a cyclopropane ring.

Nat Chem Biol 2017 Oct 7;13(10):1063-1065. Epub 2017 Aug 7.

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.

Despite containing an α-amino acid, the versatile cofactor S-adenosylmethionine (SAM) is not a known building block for nonribosomal peptide synthetase (NRPS) assembly lines. Here we report an unusual NRPS module from colibactin biosynthesis that uses SAM for amide bond formation and subsequent cyclopropanation. Our findings showcase a new use for SAM and reveal a novel biosynthetic route to a functional group that likely mediates colibactin's genotoxicity.
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http://dx.doi.org/10.1038/nchembio.2448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5657534PMC
October 2017

Versatile Solution-Processed Synthesis of Two-Dimensional Ultrathin Metal Chalcogenides Following Frank-van der Merwe Growth.

ACS Appl Mater Interfaces 2017 Aug 7;9(32):27102-27110. Epub 2017 Aug 7.

Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Hubei University , Wuhan 430062, PR China.

Two-dimensional (2D) ultrathin metal chalcogenides represent a class of promising materials for various applications thanks to attractive physicochemical properties. However, a reliable pathway for fabricating ultrathin metal chalcogenides nanosheets, regardless of the bulk crystals of their 3D counterparts, still remains a challenge. Herein, we present a versatile solution-processed template synthesis strategy, in which a single molecular-level precursor anneals to ultrathin single-crystal nanosheets with the aid of lattice-matching templates, following the Frank-van der Merwe growth mode and featuring high quality, low cost, scalability, and processability. Following this strategy, SbS, MoS, and ZnS nanosheets are successfully prepared as representatives for materials whose bulk counterparts possess 1D, 2D, and 3D crystal structures, respectively, and the growth mechanism is confirmed by crystal mode analysis. As a proof-of-concept application, MoS and SbS nanosheets are used for gas sensor and flexible photodetector applications, respectively, which exhibit excellent performance. The method can also be easily extended to other ultrathin nanosheets like single metals, metal oxide, metal nitride, and heterostructures.
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http://dx.doi.org/10.1021/acsami.7b04765DOI Listing
August 2017

The safety and feasibility of diagnostic acoustic radiation force impulse elastography used for eyes. A preliminary in vivo study.

Med Ultrason 2017 Apr;19(2):185-189

Department of Ultrasound, Yancheng Institute of Clinical (The First People's Hospital of Yancheng), Xuzhou Medical University, Yancheng, Jiangsu Province, P.R. China.

Aims: To assess the safety and feasibility of acoustic radiation force impulse (ARFI) elastography in the eyes of rats. Material and methods: One hundred and twenty-six SD rats were divided into 7 groups. Group 1 was the control group and Group 2 to Group 7 were investigated by ARFI elastography using increased powers of 5%, 10%, 20%, 50%, and 100% and repetitions of 5 or 10. The changes of ocular architecture structures and functions were examined by phthalmoscopic, histopathologic, and light reflex examination, and the expression level of IL-6, IL-8, and TNF-α was determined in days 1, 3, and 7 after ARFI elastography, respectively.

Results: A satisfactory ARFI elastography was obtained in all SD rats. The shear wave velocity (SWV) values of soft tissues behind the eyeball were significantly greater than those of the eyes (1.89±0.95 vs. 0.84±0.36 m/s, p<0.05). The SWV values of eyes and the soft tissues behind the eyeball did not differ among any groups at any time-point (p>0.05). The SD rats of each group showed good light perception, pupillary light reflex, and avoidance reaction induced by the sudden bright light from the dark environment at any time. In each group, ocular architecture structures were well preserved, and with a normal expression level of IL-6, IL-8, and TNF-α (p>0.05).

Conclusions: Diagnostic ARFI elastography is a safe and feasible ultrasonic imaging mode and may potentially be applied for human eyes in its present form.
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http://dx.doi.org/10.11152/mu-996DOI Listing
April 2017

Direct Aqueous Dispersion of Carbon Nanotubes Using Nanoparticle-Formed Fullerenes and Self-Assembled Formation of p/n Heterojunctions with Polythiophene.

ACS Omega 2017 Apr 25;2(4):1625-1632. Epub 2017 Apr 25.

Nano Medical Engineering Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

Single-walled carbon nanotubes (SWCNTs) have received much attention because of their potential in optoelectronic applications. Pristine SWCNTs exhibit substantial van der Waals interactions and hydrophobic characteristics, so precipitation occurs immediately in most organic solvents and water. Highly toxic and hazardous chemicals are often used to obtain well-dispersed SWCNTs. Developing environmentally friendly processing methods for safe and practical applications is a great challenge. Here, we demonstrate direct exfoliation of SWCNTs in pure water only with n-type semiconducting fullerene nanoparticles. The resultant SWCNTs can be well-dispersed in water, where they remain essentially unchanged for several weeks. Adding an aqueous solution of p-type semiconducting water-soluble polythiophene yields self-assembled p/n heterojunctions between polythiophene and the nanoparticles. The aqueous-dispersed SWCNTs yield photocurrent responses in solution-processed thin films as a potential application of water-dispersed carbon nanomaterials.
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http://dx.doi.org/10.1021/acsomega.7b00175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6641165PMC
April 2017

Nested-PCR assay for detection of Schistosoma japonicum infection in domestic animals.

Infect Dis Poverty 2017 Apr 13;6(1):86. Epub 2017 Apr 13.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Key Laboratory of Animal Parasitology, Ministry of Agriculture, Shanghai, 200241, People's Republic of China.

Background: Schistosomiasis japonica is a common zoonosis. Domestic animals are the primary source of infection and play an important role in disease transmission. The prevalence and infectivity of this disease in domestic animals in China have significantly decreased and, for this reason, diagnostics with a higher sensitivity have become increasingly necessary. It was reported that polymerase chain reaction (PCR)-based methods could be used to detect schistosome infection in humans and animals and presented a high sensitivity and specificity. The present study aimed to develop a PCR-based method for detection of Schistosoma japonicum infection in domestic animals.

Methods: A specific nested-PCR assay was developed to detect S. japonicum infection in domestic animals via amplification of a 231-bp DNA fragment of retrotransposon SjR2. The developed assay was first used in sera and dry blood filter paper (DBFP) from goats and buffaloes at different time points of infection. Then, 78 DBFPs from 39 artificially-infected bovines at 14 and 28 days post-infection and 42 DBFPs from schistosome-negative bovines from the city of Huangshan in the Anhui province were used to evaluate the diagnostic validity. Furthermore, this assay was used to detect S. japonicum infection in domestic animals in Dongzhi and Wangjiang counties.

Results: The expected PCR product was detected in eggs and adult worms of S. japonicum and blood samples from S. japonicum-infected goats and water buffaloes, but not from Fasciola and Haemonchus contortus worms. The nested-PCR assay could detect the target S. japonicum DNA in DBFPs from goats and buffaloes after day 3 post-infection. The sensitivity in buffaloes at 14 and 28 days post-infection was 92.30% (36/39) and 100% (39/39), respectively. The specificity was 97.60% (41/42). The positivity rates in Dongzhi and Wangjiang counties were 6.00% and 8.00% in bovines and 22.00% and 16.67% in goats, respectively. The positivity rates in goats in both counties were higher than those in bovines with a significant difference in Dongzhi County but not in Wangjiang County (P < 0.05 and P = 0.23, respectively).

Conclusions: Our results suggest that the developed nested-PCR assay may be used for the diagnosis of S. japonicum infection in domestic animals, and the control of S. japonicum infection in goats should be paid more attention.
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http://dx.doi.org/10.1186/s40249-017-0298-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390378PMC
April 2017

Natural product discovery from the human microbiome.

J Biol Chem 2017 05 7;292(21):8546-8552. Epub 2017 Apr 7.

From the Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138

Human-associated microorganisms have the potential to biosynthesize numerous secondary metabolites that may mediate important host-microbe and microbe-microbe interactions. However, there is currently a limited understanding of microbiome-derived natural products. A variety of complementary discovery approaches have begun to illuminate this microbial "dark matter," which will in turn allow detailed mechanistic studies of the effects of these molecules on microbiome and host. Herein, we review recent efforts to uncover microbiome-derived natural products, describe the key approaches that were used to identify and characterize these metabolites, discuss potential functional roles of these molecules, and highlight challenges related to this emerging research area.
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http://dx.doi.org/10.1074/jbc.R116.762906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5448083PMC
May 2017

Lead-Free, Blue Emitting Bismuth Halide Perovskite Quantum Dots.

Angew Chem Int Ed Engl 2016 11 28;55(48):15012-15016. Epub 2016 Oct 28.

Wuhan National Laboratory for Optoelectronics (WNLO) and School of Optical and Electronic Information, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.

Lead halide perovskite quantum dots (QDs) are promising candidates for future lighting applications, due to their high quantum yield, narrow full width at half maximum (FWHM), and wide color gamut. However, the toxicity of lead represents a potential obstacle to their utilization. Although tin(II) has been used to replace lead in films and QDs, the high intrinsic defect density and oxidation vulnerability typically leads to unsatisfactory material properties. Bismuth, with much lower toxicity than lead, is promising to constitute lead-free perovskite materials because Bi is isoelectronic to Pb and more stable than Sn . Herein we report, for the first time, the synthesis and optical characterization of MA Bi Br perovskite QDs with photoluminescence quantum yield (PLQY) up to 12 %, which is much higher than Sn-based perovskite nanocrystals. Furthermore, the photoluminescence (PL) peaks of MA Bi X QDs could be easily tuned from 360 to 540 nm through anion exchange.
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http://dx.doi.org/10.1002/anie.201608160DOI Listing
November 2016

The value of pancreatic stone protein in the prediction of infected neonates.

Minerva Pediatr 2017 Dec 17;69(6):489-494. Epub 2016 Mar 17.

Department of Neonatology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.

Background: The aim of this study was to determine serum pancreatic stone protein (PSP) levels in the neonates with highly probable or probable sepsis and assess their possible value in predicting infected neonates.

Methods: This was a prospective study involving 119 neonates who were admitted with suspected sepsis. The study population was divided into two groups, a infected group (N.=40, with highly probable sepsis or probable sepsis) and control group (N.=79, with possible or no sepsis). The blood samples were obtained at 24, 72 and 168 hours after birth. The amount of serum PSP were detected by enzyme linked immunosorbent (ELISA).

Results: PSP serum concentrations were higher in the infected group comparison to the control group at all time points (all P=0.000). In addition the sequential comparison between the infected group and control group at all of time points was significantly different (F=48.558, P=0.000). ROC area under the curve (AUC) was 0.791 [95% CI: 0.71-0.87; P=0.000] for PSP at 24 hours after birth and 0.790 (95% CI: 0.79-0.88; P=0.000) 72 hours after birth and combination of the two time points (24 and 72 hours), the AUC was 0.819 (95% CI: 0.74-0.90; P=0.000).

Conclusions: PSP is a valuable biomarker in predicting infected neonates. Combination of PSP at each time point within 72 hours after birth might be better.
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http://dx.doi.org/10.23736/S0026-4946.16.04317-XDOI Listing
December 2017

[Effects of ridge-cultivation and plastic film mulching on root distribution and yield of spring maize in hilly area of central Sichuan basin, China.]

Ying Yong Sheng Tai Xue Bao 2016 Mar;27(3):855-862

College of Agronomy, Sichuan Agricultural University/Key Laboratory of Crop Ecophysiology and Farming System in Southwest China, Chengdu 611130, China.

A field experiment was conducted to study the effects of planting pattern (ridge culture, flatten culture, furrow culture) and film mulching on the distribution of spring maize root system and their influence on the yield of spring maize in the hilly area of central Sichuan basin. The results showed that ridge and film mulching had great influence on root morphology and root distribution of maize. The root length, root surface area and root volume of film mulching was 42.3%, 50.0%, 57.4% higher than those of no film mulching at jointing stage. The film mulching significantly increased the dry mass of root in vertical and horizontal distribution, and increased the root allocation ratio in deeper soil layer (20-40 cm) and the allocation ratio of wide row (0-20 cm) in horizontal direction. The effects of planting pattern on root growth and root distribution differed by film mulching. With film mulching, the ridge culture significantly increased the root dry mass in each soil layer and enlarged the distribution percentage of wide row (20-40 cm) in horizontal direction, as well as the dry mass of root in horizontal distribution and the root allocation ratio of wide row. The root mass under film mulching was in the order of ridge culture>flatten culture>furrow culture. Without film mulching, the furrow culture significantly increased root dry mass of narrow row (0-40 cm), and the root mass under no film mulching was in the order of furrow culture > ridge culture >flatten culture. As for the spike characteristics and maize yield, the filming mulching mea-sures reduced the corn bald length while increased the spike length, grain number, 1000-grain mass and yield. The yield under film mulching was in the order of ridge culture>flatten culture> furrow culture, while it was furrow culture > flatten culture > ridge culture under no film mulching. The reason for yield increase under ridge culture with film mulching was that it increased root weight especially in deep soil, and promoted the root allocation ratio in deeper soil and wide row (20-40 cm) in horizontal direction. The ridge-furrow culture without film mulching was helpful to root growth and increased the maize yield.
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http://dx.doi.org/10.13287/j.1001-9332.201603.023DOI Listing
March 2016

Characterization of Polyketide Synthase Machinery from the pks Island Facilitates Isolation of a Candidate Precolibactin.

ACS Chem Biol 2016 05 1;11(5):1287-95. Epub 2016 Mar 1.

Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.

Colibactin is a human gut bacterial genotoxin of unknown structure that has been linked to colon cancer. The biosynthesis of this elusive metabolite is directed by the pks gene cluster, which encodes a hybrid nonribosomal peptide synthetase-polyketide synthase (NRPS-PKS) assembly line that is hypothesized to use the unusual polyketide building block aminomalonate. This biosynthetic pathway is thought to initially produce an inactive intermediate (precolibactin) that is processed to the active toxin. Here, we report the first in vitro biochemical characterization of the PKS components of the pks enzymatic assembly line. We evaluate PKS extender unit utilization and show that ClbG, a freestanding acyltransferase (AT) from the pks gene cluster, recognizes aminomalonyl-acyl carrier protein (AM-ACP) and transfers this building block to multiple PKS modules, including a cis-AT PKS ClbI. We also use genetics to explore the in vivo role of ClbG in colibactin and precolibactin biosynthesis. Unexpectedly, production of previously identified pks-associated metabolites is dramatically increased in a ΔclbP/ΔclbG mutant strain, enabling the first structure elucidation of a bithiazole-containing candidate precolibactin. This work provides new insights into the unusual biosynthetic capabilities of the pks gene cluster, offers further support for the hypothesis that colibactin directly damages DNA, and suggests that additional, uncharacterized pks-derived metabolites containing aminomalonate play critical roles in genotoxicity.
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http://dx.doi.org/10.1021/acschembio.6b00014DOI Listing
May 2016

Tumor boundary detection in ultrasound imagery using multi-scale generalized gradient vector flow.

J Med Ultrason (2001) 2015 Jan 5;42(1):25-38. Epub 2014 Aug 5.

Ultrasonic Department, Hubei Cancer Hospital, 116 Zhuodaoquan South Road, Wuchang District, Wuhan, 430079, China.

Purpose: As a key technology in high-intensity focused ultrasound (HIFU) ablation systems, a precise ultrasound image segmentation method for tumor boundary detection is helpful for ablation of tumors and avoiding tumor recurrence. This study explores a new deformable snake model called multi-scale generalized gradient vector flow (MS-GGVF) to segment ultrasound images in HIFU ablation.

Methods: The main idea of the technique is dealing with two issues including spurious boundary attenuation and setting the standard deviation of the Gaussian filter. We assign the standard deviation as scales to build the MS-GGVF model and create a signed distance map to use its gradient direction information and magnitude information to refine the multi-scale edge map by attenuating spurious boundaries and highlighting the real boundary. In addition, a fast generalized gradient vector flow computation algorithm based on an augmented Lagrangian method is introduced to calculate the external force vector field to improve the computation efficiency of our model.

Results: The experimental segmentations were similar to the ground truths delineated by two medical physicians with high area overlap measure and low mean contour distance.

Conclusion: The experimental results demonstrate that the proposed algorithm is robust, reliable, and precise for tumor boundary detection in HIFU ablation systems.
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http://dx.doi.org/10.1007/s10396-014-0559-3DOI Listing
January 2015

Plasma level of soluble receptor for advanced glycation end-products and aquaporin 5 in preterm infants with acute respiratory distress syndrome.

Minerva Pediatr 2016 Oct 16;68(5):360-5. Epub 2015 Apr 16.

Neonatal Medical Center, Huai'an Maternity and Child Healthcare Hospital, Yangzhou University Medical School. No.104, Huai'an, China -

Background: The aim of this study was to determine the plasma level of soluble receptors for advanced glycation end-products (sRAGE) and aquaporin 5 (AQP5) in preterm infants with acute respiratory distress syndrome (RDS).

Methods: Forty-three preterm infants diagnosed with RDS were the experimental group. Ten apparently healthy preterm neonate infants were as normal controls. The experimental group was further divided into three subgroups based on PaO2/FiO2 (P/F): the mild group (200


Results: The plasma levels of sRAGE and AQP5 of the control group were significantly lower than that of experimental group at three time points (all P<0.05). The severity of RDS in preterm infants seemed to be associated with the plasma level of sRAGE and AQP5: the more severe the disease, the higher the plasma level of sRAGE and AQP5.

Conclusions: The plasma level of sRAGE and AQP5 might be associated with the severity of RDS in preterm infants.

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October 2016

Solubilization of single-walled carbon nanotubes using a peptide aptamer in water below the critical micelle concentration.

Langmuir 2015 Mar 13;31(11):3482-8. Epub 2015 Mar 13.

†Nano Medical Engineering Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

The solubilizing ability of single-walled carbon nanotubes (SWCNTs) in water with several dispersants was investigated. Among the dispersants, including low-molecular-weight surfactants, peptides, DNA, and a water-soluble polymer, the peptide aptamer, A2 (IFRLSWGTYFS), exhibited the highest dispersion capability below the critical micelle concentration at a concentration of 0.02 w/v%. The dispersion of supernatant aqueous solution of SWCNTs containing aptamer A2 was essentially unchanged for several months after high-speed ultracentrifugation and gave rise to an efficient and stable dispersion of the SWCNTs in water. From the results of isothermal titration calorimetry and molecular dynamics simulations, the effective binding capability of A2 was due to π-π interaction between aromatic groups in the peptide aptamer and the side walls of SWCNTs. Interestingly, the peptide aptamer showed the possibility of diameter separation of semiconducting SWCNTs using a uniform density gradient ultracentrifuge. These phenomena are encouraging results toward an effective approach to the dispersion and separation of SWCNTs.
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http://dx.doi.org/10.1021/la504777bDOI Listing
March 2015

[Application of lung recruitment maneuver in preterm infants with respiratory distress syndrome ventilated by proportional assist ventilation].

Zhonghua Er Ke Za Zhi 2014 Oct;52(10):741-4

Department of Neonatology, Bayi Children's Hospital Affiliated to General Hospital of Beijing Military Command, Beijing 100700, China.

Objective: To understand the effect of lung recruitment maneuver (LRM) with positive end-expiratory pressure (PEEP) on oxygenation and outcomes in preterm infants with respiratory distress syndrome (RDS) ventilated by proportional assist ventilation (PAV).

Method: From January 2012 to June 2013, thirty neonates with a diagnosis of RDS who required mechanical ventilation were divided randomly into LRM group (n=15, received an LRM and surport by PAV) and control group (n=15, only surport by PAV). There were no statistically significant differences in female (7 vs. 6); gestational age [(29.3±1.2) vs. (29.5±1.1) weeks]; body weight[(1,319±97) vs. (1,295±85) g]; Silverman Anderson(SA) score for babies at start of ventilation (7.3±1.2 vs. 6.9±1.4); initial FiO2 (0.54±0.12 vs. 0.50±0.10) between the two groups (all P>0.05). LRM entailed increments of 0.2 cmH2O (1 cmH2O=0.098 kPa) PEEP every 5 minutes, until fraction of inspired oxygen (FiO2)=0.25. Then PEEP was reduced and the lung volume was set on the deflation limb of the pressure/volume curve.When saturation of peripheral oxygen fell and FiO2 rose, we reincremented PEEP until SpO2 became stable. The related clinical indicators of the two group were observed.

Result: The doses of surfactant administered (1.1±0.3 vs. 1.5±0.5, P=0.027), Lowest FiO2 (0.29±0.05 vs. 0.39±0.06, P=0.000), time to lowest FiO2[ (103±18) vs. (368±138) min, P=0.000] and O2 dependency [(7.6±1.0) vs.( 8.8±1.3) days, P=0.021] in LRM group were lower than that in control group (all P<0.05). The maximum PEEP during the first 12 hours of life [(8.4±0.8) vs. (6.8±0.8) cmH2O, P=0.000] in LRM group were higher than that in control group (P<0.05). FiO2 levels progressively decreased (F=35.681, P=0.000) and a/AO2 Gradually increased (F=37.654, P=0.000). No adverse events and no significant differences in the outcomes were observed.

Conclusion: LRM can reduce the doses of pulmonary surfactant administered, time of the respiratory support and the oxygen therapy in preterm children with RDS.
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October 2014