Publications by authors named "Lu Sun"

559 Publications

Nitrate dose-responsive transcriptome analysis identifies transcription factors and small secreted peptides involved in nitrogen response in Tartary buckwheat.

Plant Physiol Biochem 2021 Feb 25;162:1-13. Epub 2021 Feb 25.

Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, School of Food and Biological Engineering, Chengdu University, Chengdu, 610106, PR China. Electronic address:

Tartary buckwheat (Fagopyrum tataricum Gaertn.) is an economically important pseudocereal crop, which can adapt well to extreme environments, including low nitrogen (LN) stress. However, little is known regarding the associated molecular mechanisms. In this study, the molecular mechanism of Tartary buckwheat roots in response to different doses of nitrate was investigated by combining physiological changes with transcriptional regulatory network. LN improved elongation and branching of lateral roots, indicating that the plasticity of lateral roots drives the adaption of Tartary buckwheat under LN condition. The roots of the seedlings that were cultivated under four N conditions were selected for RNA-Seq analysis. In total 1686 nitrate dose-responsive genes were identified. Of these genes, 16 genes encoding N transporters showed response to N availability, and they may play important roles in N transport and root system architecture in Tartary buckwheat roots. 108 transcription factors (TFs) showed dose-response to N availability, and they may regulate N response and root growth under varied N conditions by modulating the expression of N transporters. A NIN-like protein, FtNLP7, was identified and it may contribute to the transcriptional regulation of N transporters. Furthermore, 81 N-responsive genes were identified as the small secreted peptides (SSPs). 48 N-responsive SSPs were annotated as hypothetical proteins and they may be the species-specific proteins of Tartary buckwheat. This paper provides useful information for further investigation of the mechanisms underlying the adaptation of Tartary buckwheat under N-deficient condition.
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http://dx.doi.org/10.1016/j.plaphy.2021.02.027DOI Listing
February 2021

Overexpression of SERPINA3 promotes tumor invasion and migration, epithelial-mesenchymal-transition in triple-negative breast cancer cells.

Breast Cancer 2021 Feb 10. Epub 2021 Feb 10.

Department of Endocrine Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Yixueyuan Road, Yuanjiagang, Yuzhong district, Chongqing, China.

Background: Recent studies have indicated that serpin peptidase inhibitor, clade A, member 3 (SERPINA3) is a potential marker associated with tumor progression, which connoted that SERPINA3 is related to malignant phenotypes in cancer. However, the biological function of SERPINA3 in breast cancer (BC) remains unclear.

Methods: Bioinformatics data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Immunohistochemical staining (IHC) was conducted to determine SERPINA3 expression. With strong aggressive abilities, triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, BT549 and MDA-MB-436) were obtained to examine SERPINA3 expression and functions. Wound healing and Transwell assays were performed to measure cell migration and invasion. Cell Counting Kit-8 (CCK-8) assay was conducted to detect cell proliferation abilities and cell viabilities.

Results: SERPINA3 was upregulated in BC tissues. Functional assays suggested that overexpression of SERPINA3 significantly promoted cell proliferation, where migration and invasion of TNBC cells were accelerated. Knockdown of SERPINA3 had the opposite effects. These results causing by overexpression of SERPINA3 were also confirmed in non-TNBC cell lines. Overexpression of SERPINA3 remarkably enhanced the epithelial-mesenchymal transition (EMT) by upregulating the EMT markers and EZH2. In addition, the overexpression of SERPINA3 reduced the sensitivity of TNBC cells to cisplatin.

Conclusion: SERPINA3 can regulate the migration, invasion and EMT of TNBC cells and increased expression of SERPINA3 confers resistance to cisplatin in TNBC cells. We discern it is required for the regulation of BC progression and is a critical target for the clinical treatment of BC.
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http://dx.doi.org/10.1007/s12282-021-01221-4DOI Listing
February 2021

Alterations of Fucosyltransferase Genes and Fucosylated Glycans in Gastric Epithelial Cells Infected with .

Pathogens 2021 Feb 4;10(2). Epub 2021 Feb 4.

State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

() adhesion to human gastric epithelial cells is closely linked with fucosylated glycans. Therefore, investigation of fucosylation in the interaction of gastric epithelial cells with is critical. In this study we used lectin microarrays to detect the expression of fucosylated glycans in gastric epithelial cells (GES-1) infected with strains isolated from patients with different diseases including chronic gastritis, duodenal ulcers, and gastric cancer (each containing two strains) at 4 h. In addition, we investigated the time-course expression of fucosyltransferase (FUT) 1-6 genes in GES-1 cells stimulated with strains at 0.5-8 h. At 4 h post-infection, Lotus, AAA, BC2LCN, PA-IIL, CNL and ACG lectins had increased signals in -infected GES-1 cells compared to uninfected cells. Higher expression of FUT1 and FUT2 was detected in all -infected GES-1 cells within 2 h, regardless of the strain. In particular, the expression of FUT2 was higher in -infected GES-1 cells with a higher fold change in levels of BC2LCN lectin specific to α1-2 linked fucose (Fuc) at 4 h. The results suggest that the high levels of α1, 2-linked Fuc synthesized by FUT1/2, might play a role in the preliminary stage of infection. This provides us with pivotal information to understand the adhesion of to human gastric epithelial cells.
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http://dx.doi.org/10.3390/pathogens10020168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913934PMC
February 2021

Evidence-based Chinese medicine for the response to public health emergencies: The Guangzhou declaration.

J Evid Based Med 2021 Feb 7;14(1):3-4. Epub 2021 Feb 7.

Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, The Second Clinical School of Guangzhou University of Chinese Medicine, Guangzhou, China.

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http://dx.doi.org/10.1111/jebm.12422DOI Listing
February 2021

Study on correlation between language retardation and screen exposure in children.

Minerva Med 2021 Jan 19. Epub 2021 Jan 19.

Department of Pediatric, Heilongjiang Provincial Hospital, Harbin, China -

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http://dx.doi.org/10.23736/S0026-4806.20.07252-3DOI Listing
January 2021

Folate-Targeted Anticancer Drug Delivery via a Combination Strategy of a Micelle Complex and Reducible Conjugation.

ACS Biomater Sci Eng 2020 Mar 25;6(3):1565-1572. Epub 2020 Feb 25.

Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study & Department of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China.

Conjugation of various active targeting ligands to the surface of nanocarriers to realize specific recognition by the corresponding receptors localized on the membrane of the cancer cells has provided a powerful means toward enhanced cancer therapy. Folic acid (FA) is one of the most used targeting ligands due to the overexpressed FA receptors in many cancer cell lines. However, conjugation of hydrophobic FA to the surface of nanocarriers usually alters the hydrophilic/hydrophobic balance of the stabilized nanoparticles, leading to their thermodynamic instability and subsequent formation of aggregates, which apparently compromises the in vivo long circulation and minimized side effects of nanocarriers. The currently leading strategy to overcome this issue is to incorporate a protecting hydrophilic stealth that can be deshielded to expose the targeting ligand at the desired tumor site, which generally involves multistep chemical modifications, conjugations, and purifications. To develop a simple alternative toward FA-mediated enhanced anticancer drug delivery, a combination strategy of micelle complex and reducible conjugation was reported in this study. FA was first conjugated to the terminus of the hydrophilic block of a reduction-sensitive miktoarm star-shaped amphiphilic copolymer, PCL-SS-POEGMA, with the previously optimized star structure by click coupling via a reducible disulfide link. The resulting PCL-SS-POEGMA-SS-FA was further mixed with the parent PCL-SS-POEGMA to afford a micelle complex with both reducibly conjugated and relatively low amount of FA-targeting ligands toward excellent FA-mediated targeted drug delivery without compromised salt stability in vitro and in vivo. Therefore, the combined strategy developed herein provides a simple and powerful means to promote FA-mediated anticancer drug delivery.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01920DOI Listing
March 2020

Natural Melanin/Polyurethane Composites as Highly Efficient Near-Infrared-Photoresponsive Shape Memory Implants.

ACS Biomater Sci Eng 2020 Sep 21;6(9):5305-5314. Epub 2020 Aug 21.

Institute for Frontier Materials, Australian Future Fibers Research and Innovation Center, Deakin University, 75 Pigdons Road, Geelong, Victoria 3220, Australia.

Natural melanin is recognized as a biocompatible photothermal agent because of its biologically derived nature and efficient photothermal conversion ability. Here, yak hair melanin (YM) is added to polyurethane (PU) for the fabrication of NIR-photoresponsive shape memory implants. The toxicity of the YM/PU composites is carried out by exposing them to human mesenchymal stem cells (hMSCs) and mouse fibroblast (L929) cells lines for 24 h, while the toxicity is investigated by implanting the YM/PU composites in the mouse for two months. No significant differences on cell viability, blood chemistry, hematology, and histological results are observed between YM/PU composites and control groups, suggesting their excellent biocompatibility. The biostability of the YM/PU composites is confirmed by monitoring their degradation for 12 weeks. The YM/PU column implanted in the back subcutis or vagina of the mouse rapidly recovered to its original state within 60 s under a very low NIR laser (808 nm, 0.5 W/cm) intensity, which is much lower than the general laser intensity for photothermal cancer therapy (1-2 W/cm). This work confirms the applicability of the YM/PU composites as long-term implant materials and expedites the use of YM/PU composites as cost-effective candidates for biomedical applications.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00933DOI Listing
September 2020

Ultra-compact and broadband silicon polarizer employing a nanohole array structure.

Opt Lett 2021 Jan;46(2):194-197

An ultra-compact and broadband transverse magnetic (TM)-pass polarizer is experimentally demonstrated using a photonic crystal nanohole structure. By engineering the period of the circular holes, the fundamental transverse electric mode is suppressed due to the bandgap of the nanohole array, while the mode propagates with a negligible insertion loss. Simulation results predict that the bandwidth of the device can reach 245 nm with a 33 dB polarization extinction ratio (PER). In the experiment, an insertion loss <1.2 for the mode and a PER over 20.8 dB are demonstrated in a 70 nm wavelength range from 1520 to 1590 nm, mainly limited by the grating couplers used for fiber-to-chip coupling. The fabricated device is compact with a total length of 7.21 µm.
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http://dx.doi.org/10.1364/OL.403819DOI Listing
January 2021

Porous Core/Dense Shell PLA Microspheres Embedded with High Drug Loading of Bupivacaine Crystals for Injectable Prolonged Release.

AAPS PharmSciTech 2021 Jan 6;22(1):27. Epub 2021 Jan 6.

School of Pharmacy, Shenyang Pharmaceutical University, No. 26 Huatuo Avenue, Benxi, 117004, People's Republic of China.

Objective of the study was to design an injectable microsphere preparation with high drug loading of bupivacaine for prolonged release and local anesthetic. PLA or PLGA was used as the biodegradable matrix material to fabricate microspheres with the o/w emulsification-solvent evaporation method. The characterization of bupivacaine microspheres was observed by SEM, DSC, and XRPD. The microsphere preparation and extended drug release, as well as the plasma drug concentration and sciatic nerve blockade after injection of the microsphere formulation to rats were investigated. High drug-loading microspheres of more than 70% were successfully obtained with extended drug release over 5 days in vitro depending on the type of matrix and the feed ratio of drug to polymer. SEM, DSC, and XRPD results verified a novel microsphere structure characterized as the porous core composed of PLA material and form II bupivacaine crystals and dense shell formed of PLA layer. The mechanism that bupivacaine was dissolved inside the microsphere and diffused across the dense shell was suggested for drug release in vitro. The optimized PLA microsphere formulation showed low and steady plasma drug concentration over 5 days and prolonged duration of sensory and motor blockade of sciatic nerve lasted more than 3 days. Results indicated that the porous core-shell structure of PLA microsphere formulation would provide enormous potential as an injectable depot for locally prolonged delivery of bupivacaine and control of postoperative pain.
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http://dx.doi.org/10.1208/s12249-020-01878-8DOI Listing
January 2021

A Meta-Analysis of Different Types of Cardiac Adipose Tissue in HIV Patients.

Biomed Res Int 2020 9;2020:8234618. Epub 2020 Dec 9.

Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China.

Background: Antiretroviral therapy transformed HIV infection into a chronic disease but accelerated cardiovascular disease (CVD). Both of epicardial adipose tissue (EAT) and pericardial fat (PCF) have close relationships with CVD. The associations between these two cardiac adipose tissue and HIV are unclear.

Methods: Eligible studies were searched in PubMed, Embase, Web of Science, and Scopus from database inception to March 24, 2020. The summarized standard mean difference (SMD) or weighted mean difference (WMD) with 95% confidence intervals (CIs) was used to assess the association between EAT/PCF and HIV. Subgroup analysis was performed based on EAT types. Trial sequential analysis was conducted to estimate whether the evidence of the results is sufficient.

Results: In total, 2561 HIV patients and 1767 non-HIV participants were included. Compared to the control group, EAT was significantly higher in the HIV overall group and subgroup with EAT thickness (SMD = 0.59, 95% CI: 0.24-0.95, = 0.001; SMD = 1.10, 95% CI: 0.41-1.79, = 0.002); however, the EAT volume and PCF volume were unchanged in the HIV group (SMD = 0.16, 95% CI: -0.07-0.39, = 0.169; WMD = 10.78, 95% CI: -14.11-35.67, = 0.396). Trial sequential analysis indicated that the available samples were sufficient in the HIV overall group and subgroup with EAT thickness, and more studies are needed for EAT volume and PCF volume.

Conclusions: EAT thickness was significantly higher in patients with HIV. The association between EAT/PCF volume and HIV needs more studies to confirm.
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http://dx.doi.org/10.1155/2020/8234618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746457PMC
December 2020

Coronavirus Endoribonuclease Ensures Efficient Viral Replication and Prevents Protein Kinase R Activation.

J Virol 2020 Dec 23. Epub 2020 Dec 23.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.

Coronavirus (CoV) nsp15 is an endoribonuclease conserved throughout the CoV family. The enzymatic activity and crystal structure of infectious bronchitis virus (IBV) nsp15 are undefined, and the protein's role in replication remains unclear. We verified the uridylate-specific endoribonuclease (EndoU) activity of IBV and found that the EndoU active sites were located in the C-terminus of nsp15 and included His223, His238, Lys278 and Tyr334. We further constructed an infectious clone of the IBV-rSD strain (rSD-wild-type [WT]) and EndoU-deficient IBVs by changing the codon for the EndoU catalytic residues to alanine. Both the rSD-WT and EndoU-deficient viruses propagated efficiently in embryonated chicken eggs. Conversely, EndoU-deficient viral propagation was severely impaired in chicken embryonic kidney cells, which was reflected in the lower viral mRNA accumulation and protein synthesis. After infecting chickens with the parental rSD-WT strain and EndoU-deficient viruses, the EndoU-deficient-virus-infected chickens presented reduced mortality, tissue injury and viral shedding. Coronaviruses can emerge from animal reservoirs into naive host species to cause pandemic respiratory and gastrointestinal diseases with significant mortality in humans and domestic animals. Infectious bronchitis virus (IBV), a γ-coronavirus, infects respiratory, renal and reproductive systems, causing millions of dollars in lost revenue worldwide annually. Mutating the viral endoribonuclease resulted in an attenuated virus and prevented protein kinase R activation. Therefore, EndoU activity is a virulence factor in IBV infections, thus providing an approach for generating live-attenuated vaccine candidates for emerging coronaviruses.
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http://dx.doi.org/10.1128/JVI.02103-20DOI Listing
December 2020

Kaempferol as an AIE-active natural product probe for selective Al detection in Arabidopsis thaliana.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Mar 10;249:119303. Epub 2020 Dec 10.

College of Science, Nanjing Forestry University, Nanjing 210037, China; Institute of Material Physics&Chemistry, Nanjing Forestry University, Nanjing 210037, China. Electronic address:

In this work, a natural product probe, kaempferol, which exhibited aggregation-induced emission (AIE) characteristic in water/tetrahydrofuran (THF) binary solvent was explored. The probe showed high resistance to photobleaching capacity and excellent selectivity towards Al in the aggregation state. Upon the addition of Al, the probe displayed more than 12-fold (I/I) fluorescence intensity enhancement, accompanied by a color change, suggesting that the aggregated kaempferol can be used as a ratiometric probe for Al detecting. Notably, promising selectivity to Al within the pH range of 6-8 made the probe suitable for physiological conditions. Further Arabidopsis thaliana root imaging experiment demonstrated that the probe could image Al in the plant.
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http://dx.doi.org/10.1016/j.saa.2020.119303DOI Listing
March 2021

Protective role of maize purple plant pigment against oxidative stress in fluorosis rat brain.

Transl Neurosci 2020 21;11(1):89-95. Epub 2020 Apr 21.

Department of Nutrition and Food Hygiene, School of Public Health, Shenyang Medical College, Shenyang, China.

In fluorosis-endemic areas, exposure to high levels of fluoride causes neurotoxicity such as lowered intelligence and cognitive impairment. Oxidative damage is critical to pathophysiologic processes of fluoride intoxication, and neurotoxicity of fluoride may be associated with oxidative stress. In previous studies, maize purple plant pigment (MPPP), which was rich in anthocyanins, showed a strong scavenging activity and . The present study aimed to determine whether treatment with MPPP can alleviate fluoride-induced oxidative damage in rat brain. After 3 months of experiment, brain tissues were assayed for oxidative stress variables, histological and Western blotting examinations. Our results showed that MPPP reduced the elevated malondialdehyde levels, increased superoxide dismutase activity, and further attenuated histopathological alterations and mitigated neuronal apoptosis. Importantly, MPPP also reversed changes in Bax and Bcl-2. Therefore, it was speculated that MPPP protects brain tissue from fluoride toxicity through its antioxidant capacity.
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http://dx.doi.org/10.1515/tnsci-2020-0055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711974PMC
April 2020

Regulation of dimethylarginine dimethylaminohydrolase 2 expression by NF-κB acetylation.

Exp Ther Med 2021 Feb 3;21(2):114. Epub 2020 Dec 3.

Department of Medical Genetics, School of Life Science, China Medical University, Shenyang, Liaoning 110122, P.R. China.

Nitric oxide (NO) serves a crucial role in the kidney and is synthesized by NO synthase (NOS). Asymmetrical dimethylarginine is an endogenous inhibitor of NOS that is metabolized by dimethylarginine dimethylaminohydrolase (DDAH). To investigate the role of acetylation in DDAH2 expression, 293 cells were treated with trichostatin A (TSA), a deacetylase inhibitor and the mRNA and protein levels were assessed using quantitative PCR and western blotting respectively. Its promoter activity was detected using a luciferase assay. The effect of TSA on NF-κB acetylation was tested after immunoprecipitation. The binding of NF-κB to the DDAH2 promoter was analyzed using an electrophoretic mobility shift assay and chromatin immunoprecipitation. TSA upregulated DDAH2 expression and transcriptional activity of the DDAH2 promoter through a NF-κB responsive element, which is located at the -1582 to -1573 position of the DDAH2 promoter. Furthermore, TSA treatment promoted NF-κB acetylation, resulting in enhanced NF-κB binding affinity to its binding site both and . Taken together, the present study demonstrated that NF-κB acetylation upregulated DDAH2 expression by enhancing the binding ability of NF-κB to the DDAH2 promoter, resulting in increased promoter activity. The results provided a possible mechanism underlying the regulation of NO production in renal cells and a potential target for treating certain NO-associated renal disorders.
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http://dx.doi.org/10.3892/etm.2020.9546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739820PMC
February 2021

Durable Suppression of Acquired MEK Inhibitor Resistance in Cancer by Sequestering MEK from ERK and Promoting Antitumor T-cell Immunity.

Cancer Discov 2021 Mar 14;11(3):714-735. Epub 2020 Dec 14.

Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California.

MAPK targeting in cancer often fails due to MAPK reactivation. MEK inhibitor (MEKi) monotherapy provides limited clinical benefits but may serve as a foundation for combination therapies. Here, we showed that combining a type II RAF inhibitor (RAFi) with an allosteric MEKi durably prevents and overcomes acquired resistance among cancers with , and mutations. Tumor cell-intrinsically, type II RAFi plus MEKi sequester MEK in RAF complexes, reduce MEK/MEK dimerization, and uncouple MEK from ERK in acquired-resistant tumor subpopulations. Immunologically, this combination expands memory and activated/exhausted CD8 T cells, and durable tumor regression elicited by this combination requires CD8 T cells, which can be reinvigorated by anti-PD-L1 therapy. Whereas MEKi reduces dominant intratumoral T-cell clones, type II RAFi cotreatment reverses this effect and promotes T-cell clonotypic expansion. These findings rationalize the clinical development of type II RAFi plus MEKi and their further combination with PD-1/L1-targeted therapy. SIGNIFICANCE: Type I RAFi + MEKi are indicated only in certain cancers. In contrast, type II RAFi + MEKi are durably active against acquired MEKi resistance across broad cancer indications, which reveals exquisite MAPK addiction. Allosteric modulation of MAPK protein/protein interactions and temporal preservation of intratumoral CD8 T cells are mechanisms that may be further exploited..
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http://dx.doi.org/10.1158/2159-8290.CD-20-0873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933113PMC
March 2021

Mucosal healing in intestinal Behçet's disease: A systematic review and meta-analysis.

J Dig Dis 2021 Feb 22;22(2):83-90. Epub 2021 Jan 22.

Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Objectives: Behçet's disease (BD) is a chronic inflammatory disease characterized by recurrent oral aphthous ulcers, intestinal lesions, genital ulcers, uveitis, and skin lesions. Evidence regarding mucosal healing for the prognosis of intestinal BD is scarce. The aim of this systematic review and meta-analysis was to determine the association between mucosal healing and long-term outcomes of patients with intestinal BD.

Methods: Relevant studies were identified in a comprehensive search of PubMed, Cochrane Library, and EMBASE databases. Studies reporting long-term outcomes of mucosal healing in patients with intestinal BD were included. Pooled risk ratio (RR) and 95% confidence interval (CI) for disease recurrence and surgery were calculated using the Mantel-Haenszel random-effects models. Heterogeneity among the eligible studies was evaluated using the Q test and I statistics.

Results: Of the 4785 studies initially identified, 8 were finally included. The pooled RR for the association between mucosal healing and disease recurrence was 0.41 (95% CI 0.30-0.57, P < 0.001). For the association between mucosal healing and the risk of surgery, the pooled RR was 0.33 (95% CI 0.17-0.63, P < 0.001). Confounding factors were adjusted in one study, whereas other studies only reported a crude association between mucosal healing and long-term outcomes without adjustment.

Conclusions: Mucosal healing is associated with a decreased risk of recurrence and surgery in intestinal BD. However, more studies are required given a small number of currently eligible studies and insufficient adjustment for confounding factors.
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http://dx.doi.org/10.1111/1751-2980.12965DOI Listing
February 2021

Computational investigation on the chiral differentiation of D- and L-penicillamine by β-cyclodextrin.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Mar 3;248:119277. Epub 2020 Dec 3.

Institute of Modern Optics, Tianjin Key Laboratory of Micro-scale Optical Information Science and Technology, Nankai University, Tianjin 300071, PR China; Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi, PR China. Electronic address:

The identification of chiral penicillamine (Pen) is of great significance for clinical medication safety. The host-guest systems formed by enantiomers and macromolecule can be applied to differentiate the chiral drugs and enable the drug delayed release. We hereby performed the dispersion corrected density functional theory (DFT-D) calculation on the complex formed by β-cyclodextrin(β-CD) and D/L-penicillamine (D/L-Pen). The diverse encapsulation configurations with different interaction energy show that both D-Pen and L-Pen tend to longitudinally embedded into the narrow aperture of β-CD with the front part of the sulfur group and the methyl group, and the interaction energy between L-Pen and β-CD is 5.47 kJ/mol(M062XD3) lower than that between D-Pen and β-CD. Based on the computed vibration frequency of host, guest, and the most stable complex, it is found that the featured peaks attributed to the vibration of the carboxyl group of guest and the skeleton vibration of complex are the most significant spectral standard to distinguish the β-CD-D/L-Pen and β-CD. Moreover, the peaks resulted from the skeleton vibration in terahertz spectra can be also used to distinguish the complex of β-CD with chiral Pen. Through the topological analysis and the Independent Gradient Model (IGM) analysis, the O-HO hydrogen bond in β-CD-D-Pen is stronger than that in β-CD-L-Pen, and the van der Waals interactions such as C-H…O,C-H…N,C-H…S, O…S and C-H…C-H have the most contributions to the intermolecular interaction in β-CD-D/L-Pen. It is also noted that the H(-OH) in D-Pen and S in L-Pen contribute the most to the intermolecular interaction with β-CD in comparison with other atoms in Pen.
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http://dx.doi.org/10.1016/j.saa.2020.119277DOI Listing
March 2021

In Situ Synthesis of a Double-Layer Chitosan Coating on Cotton Fabric to Improve the Color Fastness of Sodium Copper Chlorophyllin.

Materials (Basel) 2020 Nov 26;13(23). Epub 2020 Nov 26.

Institute for Frontier Materials, Deakin University, Geelong 3220, Australia.

Natural dye's poor affinity for cotton and poor fastness properties still hinder its applications in the textile industry. In this study, a doubled-layered chitosan coating was cured on cotton fabric to serve as bio-mordant and form a protective layer on it. Under the optimal treatment conditions, the maximum (adsorption amount) of the natural dye sodium copper chlorophyllin (SCC) calculated from the Langmuir isothermal model was raised from 4.5 g/kg to 19.8 g/kg. The dye uptake of the treated fabric was improved from 22.7% to 96.4% at 1% o.w.f. dye concentration. By a second chitosan layer cured on the dyed fabric via the cross-linking method, the wash fastness of the cotton fabric dyed with SCC can be improved from 3 to 5 (ISO 105 C-06). The natural source of the biopolymer material, chitosan, and its ability to biodegrade at end of life met with the initial objective of green manufacturing in applying natural dyes and natural materials to the textile industry.
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http://dx.doi.org/10.3390/ma13235365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730442PMC
November 2020

Additional Benefit of Chinese Medicine Formulae Including for Diabetes Mellitus: Current State of Evidence.

Front Endocrinol (Lausanne) 2020 10;11:553288. Epub 2020 Nov 10.

The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Background: Chinese medicine has been used to treat diabetes symptoms for thousands of years. or is a Chinese medicinal herb that is routinely used in the treatment of diabetes mellitus (DM).

Objective: The purpose of this study is to evaluate the evidence of the added benefits and safety of herbal formulae containing in clinical studies and the possible mechanisms of in the prevention and treatment of DM in experimental studies.

Methods: We searched nine databases for randomized controlled trials (RCTs) that included in the formulae in the treatment of type 2 DM. Furthermore, experimental studies on the prevention and treatment of DM by in English- and Chinese-language databases were identified.

Results: Fifty-three moderate quality RCTs with herbal formulae containing were identified. Results from meta-analysis indicated that alone or formulae containing in addition to conventional treatments could benefit people with type 2 DM in lowering blood glucose, blood lipids and reducing insulin resistance. Moreover, adverse events were significantly lower in the CHM plus conventional group than those in the conventional group. may exert the benefit through various mechanisms including inhibition of -glucosidase and DPP-IV activity, increase of endogenous GLP-1 and immune regulating activities.

Conclusion: Evidence from this review suggested that there appeared to be added clinical benefits associated with the use of for DM, whether as a food supplement or as a CHM combined with hypoglycemic agents with a good safety profile.
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http://dx.doi.org/10.3389/fendo.2020.553288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685178PMC
November 2020

Characteristics and survival prognosis of patients with pure squamous cell carcinoma of the gallbladder.

ANZ J Surg 2020 Nov 24. Epub 2020 Nov 24.

Department of Hepatobiliary & Pancreatovascular Surgery, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, China.

Background: Pure squamous cell carcinoma (SCC) of the gallbladder is rare and often confused with the adenosquamous carcinoma (ASC) subtype in previous studies. The present study was attempted to differentiate SCC from ASC by resolving their characteristics and prognosis.

Methods: The Surveillance, Epidemiology, and End Results database was queried for SCC and ASC of gallbladder cases from 1988 to 2015. Patients' clinicopathological characteristics and survival were analysed between the groups.

Results: Of the 709 patients with primary gallbladder cancer included in this study, 249 (35.1%) had pure SCC and the remaining 460 (64.9%) had ASC. It was found that pure SCC was associated with a larger median tumour size (58.0 versus 41.0 mm, P < 0.001), while ASC presented with a worse histological grade (47.4% versus 37.8% for grades III-IV, P = 0.019) and more lymph node invasion (27.4% versus 18.9%, P = 0.041). The 3-year overall survival and disease-specific survival rates in pure SCC were lower than those in ASC (7.5% versus 11.5% for overall survival, P < 0.001; 6.2% versus 10.9% for disease-specific survival, P < 0.001). Multivariate analysis showed that early Surveillance, Epidemiology, and End Results historic stage, treatment with surgery and chemotherapy were significant favourable prognostic factors for pure SCC, while tumour size, late study period, treatment with surgery and radiotherapy were significant predictors for ASC.

Conclusion: There were significant differences in the clinicopathological characteristics and survival prognosis between pure SCC and ASC. Surgery combined with chemotherapy is the preferred treatment option for pure SCC.
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http://dx.doi.org/10.1111/ans.16452DOI Listing
November 2020

Choroidal thickening in retinal vein occlusion patients with serous retinal detachment.

Graefes Arch Clin Exp Ophthalmol 2020 Nov 18. Epub 2020 Nov 18.

Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.

Purpose: To evaluate choroid thickness and macular retinal metrics in treatment naïve retinal vein occlusion (RVO) patients with serous retinal detachment (SRD) before and after intravitreal anti-vascular endothelial cell growth factor (VEGF) injection and to elucidate the possible role of choroid in the development of SRD and the potential role of SRD as a prognostic parameter.

Methods: This is a retrospective study involving 85 RVO patients, 41 central retinal vein occlusion (CRVO), and 44 branch retinal vein occlusion (BRVO), with macular edema: 21 central retinal vein occlusion and 22 branch retinal vein occlusion with SRD and the rest without SRD. Patients were evaluated with ophthalmic examinations and swept-source optical coherence tomography (SS-OCT) both before and 4-6 weeks after intravitreal anti-VEGF treatment. Choroid thickness and retinal metrics were measured and compared between SRD and non-SRD groups within each RVO subtype.

Results: In both CRVO and BRVO patients, the mean central subfield foveal thickness (CSFT) and central subfoveal choroid thickness (CSCT) of the SRD groups were thicker than those in the non-SRD groups (p < 0.05) at onset. After one anti-VEGF injection, CSFT and FNRT decreased in all groups (p < 0.05). The CSCTs were thicker in the SRD groups compared with the non-SRD groups (p < 0.05). The mean changes of CSFT were more remarkable in the SRD groups (p < 0.05).

Conclusion: Thicker choroid was a feature of naïve RVO patients with SRD and SRD may be an indicator of better anatomical recovery of retina in RVO patients after a single dose of anti-VEGF treatment.
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http://dx.doi.org/10.1007/s00417-020-04983-3DOI Listing
November 2020

Distinct oligodendrocyte populations have spatial preference and different responses to spinal cord injury.

Nat Commun 2020 11 17;11(1):5860. Epub 2020 Nov 17.

Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, Biomedicum, 17177, Stockholm, Sweden.

Mature oligodendrocytes (MOLs) show transcriptional heterogeneity, the functional consequences of which are unclear. MOL heterogeneity might correlate with the local environment or their interactions with different neuron types. Here, we show that distinct MOL populations have spatial preference in the mammalian central nervous system (CNS). We found that MOL type 2 (MOL2) is enriched in the spinal cord when compared to the brain, while MOL types 5 and 6 (MOL5/6) increase their contribution to the OL lineage with age in all analyzed regions. MOL2 and MOL5/6 also have distinct spatial preference in the spinal cord regions where motor and sensory tracts run. OL progenitor cells (OPCs) are not specified into distinct MOL populations during development, excluding a major contribution of OPC intrinsic mechanisms determining MOL heterogeneity. In disease, MOL2 and MOL5/6 present different susceptibility during the chronic phase following traumatic spinal cord injury. Our results demonstrate that the distinct MOL populations have different spatial preference and different responses to disease.
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http://dx.doi.org/10.1038/s41467-020-19453-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673029PMC
November 2020

The Dynamic Viscoelasticity of Dental Soft Polymer Material Containing Citrate Ester-Based Plasticizers.

Materials (Basel) 2020 Nov 11;13(22). Epub 2020 Nov 11.

Division of Advanced Prosthetic Dentistry, Graduate School of Dentistry, Tohoku University, Sendai 980-8575, Japan.

The aim of this study was to investigate the dynamic viscoelasticity of dental soft polymer material containing citrate ester-based plasticizers. Three kinds of citrate ester-based plasticizer (Citroflex C-2: TEC, Citroflex A-2: ATEC, and Citroflex A-4: ATBC), with the combination of 5 wt% ethyl alcohol, were used as the liquid phase. The dynamic viscoelastic properties of nine ethyl methacrylate polymers: (A, B, C, D, E, F, G, H, and I) were immersed in 37 °C distilled water for 0, 1, 3, 7, 14 and 30 days, respectively. The dynamic viscoelastic properties were measured at 37 °C with an automatic dynamic mechanical analyzer. The shear storage modulus (), shear loss modulus (″), and loss tangent (tan ) were determined at 1 Hz. These parameters were statistically analyzed by two-way and one-way ANOVA and Tukey's multiple comparison test at a predetermined significance level of 0.05. A significant difference was found among the materials in terms of the dynamic viscoelasticity. The materials containing citrate ester-based plasticizer ATBC showed the most stable dynamic viscoelasticity. Considering the limitations of this study, the results suggest that the inclusion of citrate ester-based plasticizer can improve the durability of dental soft polymer materials.
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http://dx.doi.org/10.3390/ma13225078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697092PMC
November 2020

The Predictive Value of Pre-therapeutic Serum Gamma-glutamyl transferase in Efficacy and Adverse Reactions to Neoadjuvant Chemotherapy among Breast Cancer Patients.

J Breast Cancer 2020 Oct 28;23(5):509-520. Epub 2020 Oct 28.

Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Purpose: Gamma-glutamyl transferase (GGT) has been reported as being involved in tumor progression. Previous studies documented a potential relationship between serum GGT level and survival outcome in several types of human malignancies. However, the association between serum GGT levels and response to neoadjuvant chemotherapy (NAC) has not yet been reported. The present study aimed to evaluate the association between pre-therapeutic serum GGT level and the efficacy, long-term survival, and adverse reactions of NAC and to investigate its role in predicting NAC sensitivity in patients with breast cancer.

Methods: A total of 129 patients were recruited and stratified into 2 groups according to serum GGT level (< 29 U/L and ≥ 29 U/L). The association between pre-therapeutic serum GGT levels and clinicopathological parameters was examined. The correlation between pre-therapeutic serum GGT levels and pathological complete response (pCR) was analyzed using univariate and multivariate logistic regression. Survival analyses of relapse-free survival (RFS) and disease-free survival (DFS) were performed. Pearson's χ test and multivariate logistic regression model were used to analyze the correlation between pre-therapeutic serum GGT levels and adverse reactions.

Results: Pre-therapeutic serum GGT levels were associated with pCR among breast cancer patients treated with NAC. Multivariate analysis showed that low-level GGT significantly increased pCR rate. Patients in the high-level GGT group had poorer survival than those in the low-level GGT group. Subgroup analysis demonstrated that serum GGT level was potentially related to RFS and DFS in the hormone receptor-positive group. Low levels of GGT are significantly associated with a higher incidence of neutropenia.

Conclusion: Pre-therapeutic serum GGT level is an independent and novel biomarker for predicting the efficiency, prognosis, and adverse reactions to NAC in breast cancer patients. Patients with low pre-therapeutic serum GGT levels are more likely to have higher pCR rates, better RFS and DFS, and higher hematologic toxicity.

Trial Registration: ClinicalTrials.gov Identifier: NCT02199418, NCT02221999.
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http://dx.doi.org/10.4048/jbc.2020.23.e59DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604370PMC
October 2020

A look into the link between centrosome amplification and breast cancer.

Biomed Pharmacother 2020 Dec 28;132:110924. Epub 2020 Oct 28.

Department of Endocrine Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 Yixueyuan Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, China. Electronic address:

Centrosome amplification (CA) is a common feature of human tumors, but it is not clear whether this is a cause or a consequence of cancer. The centrosome amplification observed in tumor cells may be explained by a series of events, such as failure of cell division, dysregulation of centrosome cycle checkpoints, and de novo centriole biogenesis disorder. The formation and progression of breast cancer are characterized by genomic abnormality. The centrosomes in breast cancer cells show characteristic structural aberrations, caused by centrosome amplification, which include: an increase in the number and volume of centrosomes, excessive increase of pericentriolar material (PCM), inappropriate phosphorylation of centrosomal molecular, and centrosome clustering formation induced by the dysregulation of important genes. The mechanism of intracellular centrosome amplification, the impact of which on breast cancer and the latest breast cancer target treatment options for centrosome amplification are exhaustively elaborated in this review.
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http://dx.doi.org/10.1016/j.biopha.2020.110924DOI Listing
December 2020

Antidepressant treatment is associated with epigenetic alterations of Homer1 promoter in a mouse model of chronic depression.

J Affect Disord 2021 Jan 26;279:501-509. Epub 2020 Oct 26.

Department of Stereotactic and Functional Neurosurgery, Medical Center - University Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany; Centre National de la Recherche Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, 67000, Strasbourg, France. Electronic address:

Background: Understanding the neurobiology of depression and the mechanism of action of therapeutic measures is currently a research priority. We have shown that the expression of the synaptic protein Homer1a correlates with depression-like behavior and its induction is a common mechanism of action of different antidepressant treatments. However, the mechanism of Homer1a regulation is still unknown.

Methods: We combined the chronic despair mouse model (CDM) of chronic depression with different antidepressant treatments. Depression-like behavior was characterized by forced swim and tail suspension tests, and via automatic measurement of sucrose preference in IntelliCage. The Homer1 mRNA expression and promoter DNA methylation were analyzed in cortex and peripheral blood by qRT-PCR and pyrosequencing.

Results: CDM mice show decreased Homer1a and Homer1b/c mRNA expression in cortex and blood samples, while chronic treatment with imipramine and fluoxetine or acute ketamine application increases their level only in the cortex. The quantitative analyses of the methylation of 7 CpG sites, located on the Homer1 promoter region containing several CRE binding sites, show a significant increase in DNA methylation in the cortex of CDM mice. In contrast, antidepressant treatments reduce the methylation level.

Limitations: Homer1 expression and promotor methylation were not analyzed in different blood cell types. Other CpG sites of Homer1 promoter should be investigated in future studies. Our experimental approach does not distinguish between methylation and hydroxymethylation.

Conclusions: We demonstrate that stress-induced depression-like behavior and antidepressant treatments are associated with epigenetic alterations of Homer1 promoter, providing new insights into the mechanism of antidepressant treatment.
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http://dx.doi.org/10.1016/j.jad.2020.10.040DOI Listing
January 2021

Synthesis, antiproliferative activities, and DNA binding of coumarin-3-formamido derivatives.

Arch Pharm (Weinheim) 2021 Feb 20;354(2):e2000236. Epub 2020 Oct 20.

College of Science, Nanjing Forestry University, Nanjing, Jiangsu, China.

Ten coumarin-3-formamido derivatives, N-benzyl-coumarin-3-carboxamide (2), N-fluorobenzyl-coumarin-3-carboxamide (3-5), N-methoxybenzyl-coumarin-3-carboxamide (6-8), N-((1-methyl-1H-imidazol-5-yl)methyl)-coumarin-3-carboxamide (9), N-(thiophen-2-ylmethyl)-coumarin-3-carboxamide (10), and N-(furan-2-ylmethyl)-coumarin-3-carboxamide (11), were synthesized and characterized. Compound 5 crystallizes in a monoclinic system P2 /c space group with four chemical formulas in a unit cell; molecules of compound 5 are self-assembled into a two-dimensional supramolecular structure by intermolecular hydrogen bonds and C⋯C π stacking. The potential anticancer effects of these compounds on HeLa (cervical carcinoma), MCF-7 (breast), A549 (lung), HepG2 (liver), and human umbilical vein (HUVEC) cells were examined. Compared with compounds 1-8 and 10-11, compound 9 exhibits potent in vitro cytotoxicity against HeLa cells and lower cytotoxicity against normal cells. Therefore, further in-depth investigations of compound 9 were performed. Absorption titration experiments and fluorescence spectroscopy studies suggested that compound 9 binds to DNA through the intercalation mode.
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http://dx.doi.org/10.1002/ardp.202000236DOI Listing
February 2021

PLGA nanoparticle-reinforced supramolecular peptide hydrogels for local delivery of multiple drugs with enhanced synergism.

Soft Matter 2020 Dec 19;16(46):10528-10536. Epub 2020 Oct 19.

Department of Chemistry, China Pharmaceutical University, Nanjing 210009, China.

Localized drug delivery offers great therapeutic efficacy at local tissues while avoiding the systemic toxicity of drugs. Yet it demands the development of structurally-stable drug carrier systems with excellent injectability, as well as the capability to facilitate controlled release of multiple drugs. Herein, we describe the design and synthesis of a supramolecular hydrogel (Cis/Peptide@NP/Irino) for the combined delivery of cisplatin (Cis) and irinotecan (Irino). The self-assembled hydrogel consisted of an inner phase of irinotecan-loaded PLGA nanoparticles (NP/Irino) and an outer phase of cisplatin-loaded peptide nanofibers (Cis/Peptide). Through the structural reinforcement of PLGA nanoparticles, the Cis/Peptide@NP/Irino hydrogel exhibited better mechanical properties than Cis/Peptide or Peptide hydrogels. With excellent shear-thinning properties, it facilitated the development of a localized drug delivery system with an improved retention time in vivo. The hydrogel incorporated two anticancer drugs, Cis and Irino, at the Peptide and PLGA domains, respectively, and exhibited a faster release of Cis prior to the continuous release of Irino in vitro. Furthermore, the Cis/Peptide@NP/Irino formulation showed a better inhibition efficacy against the proliferation of cancerous A549 cells, with the synergism of Cis and Irino exceeding that of the simple solution mixtures, which was plausibly due to the enhanced cellular uptake of drugs through endocytosis. We believe that structurally-stable supramolecular hydrogels show great promise in the local delivery of various drug combinations for cancer therapy.
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http://dx.doi.org/10.1039/d0sm01152eDOI Listing
December 2020

Effects of ultrafine grinding time on the functional and flavor properties of soybean protein isolate.

Colloids Surf B Biointerfaces 2020 Dec 8;196:111345. Epub 2020 Sep 8.

Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing 100048, China. Electronic address:

Soybean protein isolate (SPI) powders were prepared at different ultrafine grinding time, and the functional and flavor properties of microparticulation SPI were evaluated. With extending ultrafine grinding time, a narrow and uniform particle size distribution in SPI powders was produced. The particle sizes of protein powders at grinding time 0, 2, 4, 6 and 8 h significantly reduced from 217 ± 16.5-137.5 ± 10.7 nm, while the absolute values of zeta-potential significantly increased from 25 ± 0.93-32.4 ± 117 mV (P < 0.05). The microstructure of SPI at grinding time 0-8 h changed from smooth to irregular. With prolonging the ultrafine grinding processing time, the solubility, foaming and emulsifying properties of SPI powders were improved, the content ofα-helix, β-sheet and random coils increased, while β-turn decreased. Furthermore, the ultrafine grinding time clearly influenced the volatile compounds of SPI powders. The main flavor compounds were aldehydes, alcohols, acids, ketones and alkanes. SPI powders for grinding time 2, 4, 6 and 8 h exhibited the higher total content of volatile compounds compared to that for 0 h. So the ultrafine grinding treatment at appropriate time could affect the functional and flavor properties of SPI.
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http://dx.doi.org/10.1016/j.colsurfb.2020.111345DOI Listing
December 2020

Association between omega-3 fatty acid supplementation and lower risk of preterm delivery: a systematic review and meta-analysis.

J Matern Fetal Neonatal Med 2020 Sep 17:1-10. Epub 2020 Sep 17.

Department of Gynecology, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China and China-Japan Friendship Hospital, Beijing, China.

Objective: To explore whether omega-3 fatty acid supplementation is associated with lower risk of preterm delivery.

Methods: Searching the RCTs which were compared preterm birth between women with omega-3 fatty acid supplementation and without before December 2019 on Medline, EMBASE and Cochrane's Library, then performing a meta-analysis.

Results: 26 trials were identified, included 20124 women. There was almost no association between omega-3 fatty acid supplementation and lower risk of preterm delivery (risk ratio 0.92, 95% confidence interval 0.85 to 1.01,  = 9%), gestational duration (0.30, -0.05 to 0.64,  = 48%). In subgroup analyses, preterm delivery lower rate occurred in groups with mixed DHA and EPA supplementation not only DHA supplementation groups (P for interaction = 0.02); The dose of equivalent greater than 1 g made a higher reduction in preterm birth significantly.

Conclusions: Omega-3 fatty acid supplementation was not associated with reduced risk of preterm delivery compared with placebo or no treatment during pregnancy. Relationship between Omega-3 fatty acid supplementation and other pregnant outcomes need more evidence and clinical studies.
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http://dx.doi.org/10.1080/14767058.2020.1785423DOI Listing
September 2020