Publications by authors named "Xin Xie"

540 Publications

Oridonin: A Review of Its Pharmacology, Pharmacokinetics and Toxicity.

Front Pharmacol 2021 5;12:645824. Epub 2021 Jul 5.

Department of Ophthalmology, School of Pharmacy, College of Medical Technology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Oridonin, as a natural terpenoids found in traditional Chinese herbal medicine (Hemsl.) H.Hara, is widely present in numerous Chinese medicine preparations. The purpose of this review focuses on providing the latest and comprehensive information on the pharmacology, pharmacokinetics and toxicity of oridonin, to excavate the therapeutic potential and explore promising ways to balance toxicity and efficacy of this natural compound. Information concerning oridonin was systematically collected from the authoritative internet database of PubMed, Elsevier, Web of Science, Wiley Online Library and Europe PMC applying a combination of keywords involving "pharmacology," "pharmacokinetics," and "toxicology". New evidence shows that oridonin possesses a wide range of pharmacological properties, including anticancer, anti-inflammatory, hepatorenal activities as well as cardioprotective protective activities and so on. Although significant advancement has been witnessed in this field, some basic and intricate issues still exist such as the specific mechanism of oridonin against related diseases not being clear. Moreover, several lines of evidence indicated that oridonin may exhibit adverse effects, even toxicity under specific circumstances, which sparked intense debate and concern about security of oridonin. Based on the current progress, future research directions should emphasize on 1) investigating the interrelationship between concentration and pharmacological effects as well as toxicity, 2) reducing pharmacological toxicity, and 3) modifying the structure of oridonin-one of the pivotal approaches to strengthen pharmacological activity and bioavailability. We hope that this review can provide some inspiration for the research of oridonin in the future.
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http://dx.doi.org/10.3389/fphar.2021.645824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289702PMC
July 2021

Identification of novel antioxidant gene signature to predict the prognosis of patients with gastric cancer.

World J Surg Oncol 2021 Jul 20;19(1):219. Epub 2021 Jul 20.

Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background: Gastric cancer (GC) commonly relates to dismal prognosis and lacks efficient biomarkers. This study aimed to establish an antioxidant-related gene signature and a comprehensive nomogram to explore novel biomarkers and predict GC prognosis.

Methods: Clinical and expression data of GC patients were extracted from The Cancer Genome Atlas database. Univariate and multivariate Cox analyses were utilized to construct a score-based gene signature and survival analyses were conducted between high- and low-risk groups. Furthermore, we established a prognostic nomogram integrating clinical variables and antioxidant-related gene signature. Its predictive ability was validated by Harrell' concordance index and calibration curves and an independent internal cohort verified the consistency of the antioxidant gene signature-based nomogram.

Results: Four antioxidant-related genes (CHAC1, GGT5, GPX8, and PXDN) were significantly associated with overall survival of GC patients but only two genes, CHAC1 (HR = 0.803, P < 0.05) and GPX8 (HR = 1.358, P < 0.05), were confirmed as independent factors. A score-based signature was constructed and could act as an independent prognosis predictor (P < 0.05). Patients with lower scores showed significantly better prognosis (P < 0.05). Comprehensive nomogram combining the antioxidant-related gene signature and clinical parameters (age, gender, grade, and stage) was established and effectively predicted overall survival of GC patients [3-year survival AUC = 0.680, C index = 0.665 (95% CI 0.614-0.716)]. The independent internal validation cohort verified the reliability and good consistency of the model [3-year survival AUC = 0.703, C index = 0.706 (95% CI 0.612-0.800)].

Conclusions: Innovative antioxidant-related gene signature and nomogram performed well in assessing GC prognoses. This study enlightened further investigation of antioxidant system and provided novel tools for GC patient management.
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http://dx.doi.org/10.1186/s12957-021-02328-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293592PMC
July 2021

Comprehensive Analysis of the SBP Family in Blueberry and Their Regulatory Mechanism Controlling Chlorophyll Accumulation.

Front Plant Sci 2021 1;12:703994. Epub 2021 Jul 1.

College of Plant Science, Jilin University, Changchun, China.

SQUAMOSA Promoter Binding Protein (SBP) family genes act as central players to regulate plant growth and development with functional redundancy and specificity. Addressing the diversity of the SBP family in crops is of great significance to precisely utilize them to improve agronomic traits. Blueberry is an important economic berry crop. However, the SBP family has not been described in blueberry. In the present study, twenty genes were identified through data mining against blueberry transcriptome databases. These VcSBPs could be clustered into eight groups, and the gene structures and motif compositions are divergent among the groups and similar within each group. The VcSBPs were differentially expressed in various tissues. Intriguingly, 10 VcSBPs were highly expressed at green fruit stages and dramatically decreased at the onset of fruit ripening, implying that they are important regulators during early fruit development. Computational analysis showed that 10 s were targeted by miR156, and four of them were further verified by degradome sequencing. Moreover, their functional diversity was studied in Arabidopsis. Noticeably, three VcSBPs significantly increased chlorophyll accumulation, and qRT-PCR analysis indicated that VcSBP13a in Arabidopsis enhanced the expression of chlorophyll biosynthetic genes such as AtDVR, AtPORA, AtPORB, AtPORC, and AtCAO. Finally, the targets of VcSBPs were computationally identified in blueberry, and the Y1H assay showed that VcSBP13a could physically bind to the promoter region of the chlorophyll-associated gene . Our findings provided an overall framework for individually understanding the characteristics and functions of the SBP family in blueberry.
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http://dx.doi.org/10.3389/fpls.2021.703994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281205PMC
July 2021

Decoration of Ru/RuO hybrid nanoparticles on MoO plane as bifunctional electrocatalyst for overall water splitting.

J Colloid Interface Sci 2021 Jul 10;604:508-516. Epub 2021 Jul 10.

Green Catalysis Center, College of Chemistry, Zhengzhou University, 100 Science Road, Zhengzhou 450001, PR China.

Hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) are the two branches of artificial overall water splitting (OWS), in which the reaction efficiency usually depends on different specific catalysts. Although effective bifunctional electrocatalyst for OWS (HER and OER) are highly desired, designing and constructing such suitable materials is full of challenges to overcome several difficulties, involving slow kinetics, differences in catalytic mechanisms, large overpotential values, and low round-trip efficiencies. In this work, we reported a new bifunctional electrocatalyst Ru/RuO-MoO catalyst (RRMC) via a redox solid phase reaction (RSPR) strategy to achieve the high electrocatalytic activity of OWS. Briefly, due to the restricted transport behavior of atoms in solid state precursor, the designed redox reaction occurred between the adjacent part of RuO and MoS, forming Ru/RuO hybrid NPs and MoO plane. Therefore, the newly formed Ru/RuO hybrid NPs and MoO plane were tightly combined and used as an electrocatalyst for OWS. Benefiting from the exposed active sites and optimized electronic structure, the RRMC sample annealed at 500 °C (RRMC-500) exhibited low overpotential for HER (18 mV) and for OER (260 mV) at 10 mA cm under alkaline conditions. Especially, a low cell voltage of 1.54 V was required at 10 mA cm under alkaline condition.
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http://dx.doi.org/10.1016/j.jcis.2021.07.038DOI Listing
July 2021

Preparation and evaluation of reduction-responsive micelles based on disulfide-linked chondroitin sulfate A-tocopherol succinate for controlled antitumour drug release.

J Pharm Pharmacol 2021 Jul 13. Epub 2021 Jul 13.

Jiangxi Provincial Key Lab of System Biomedicine, Jiujiang University, Jiujiang, China.

Objectives: The study was to construct reduction-responsive chondroitin sulfate A (CSA)-conjugated TOS (CST) micelles with disulfide bond linkage, which was used for controlled doxorubicin (DOX) release and improved drug efficacy in vivo.

Methods: CST and non-responsive CSA-conjugated TOS (CAT) were synthesized, and the chemical structure was confirmed by Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy, fluorescence spectrophotometer and dynamic light scattering. Antitumour drug DOX was physically encapsulated into CST and CSA by dialysis method. Cell uptake of DOX-based formulations was investigated by confocal laser scanning microscopy. In vitro cytotoxicity was studied in A549 and AGS cells. Furthermore, antitumour activity was evaluated in A549-bearing mice.

Key Findings: CST and CAT can form self-assembled micelles, and have low value of critical micelle concentration. Notably, DOX-containing CST (D-CST) micelles demonstrated reduction-triggered drug release in glutathione-containing media. Further, reduction-responsive uptake of D-CST was observed in A549 cells. In addition, D-CST induced stronger cytotoxicity (P < 0.05) than DOX-loaded CAT (D-CAT) against A549 and AGS cells. Moreover, D-CST exhibited significantly stronger antitumour activity in A549-bearing nude mice than doxorubicin hydrochloride and D-CAT.

Conclusions: The reduction-responsive CST micelles enhanced the DOX effect at tumour site and controlled drug release.
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http://dx.doi.org/10.1093/jpp/rgab096DOI Listing
July 2021

Nickel-Catalyzed C(sp)-H Functionalization of Benzyl Nitriles: Direct Michael Addition to Terminal Vinyl Ketones.

Org Lett 2021 Jul 8. Epub 2021 Jul 8.

Department of Chemistry, Zhengzhou University, 100 Science Avenue, Zhengzhou, Henan 450001, People's Republic of China.

An efficient nickel(0)-catalyzed addition of benzyl nitriles to terminal vinyl ketones via C(sp)-H functionalization has been developed. The reaction provides a novel and efficient protocol for the synthesis of α-functionalized benzyl nitriles with a wide range of structural diversity under mild reaction conditions while obviating the use of a strong base. The work might be potentially useful toward the development of an enantioselective variant using chiral nitrogen ligands.
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http://dx.doi.org/10.1021/acs.orglett.1c02074DOI Listing
July 2021

Low-threshold topological nanolasers based on the second-order corner state.

Light Sci Appl 2020 Jun 29;9(1):109. Epub 2020 Jun 29.

Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, 100190, China.

Topological lasers are immune to imperfections and disorder. They have been recently demonstrated based on many kinds of robust edge states, which are mostly at the microscale. The realization of 2D on-chip topological nanolasers with a small footprint, a low threshold and high energy efficiency has yet to be explored. Here, we report the first experimental demonstration of a topological nanolaser with high performance in a 2D photonic crystal slab. A topological nanocavity is formed utilizing the Wannier-type 0D corner state. Lasing behaviour with a low threshold of approximately 1 µW and a high spontaneous emission coupling factor of 0.25 is observed with quantum dots as the active material. Such performance is much better than that of topological edge lasers and comparable to that of conventional photonic crystal nanolasers. Our experimental demonstration of a low-threshold topological nanolaser will be of great significance to the development of topological nanophotonic circuitry for the manipulation of photons in classical and quantum regimes.
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http://dx.doi.org/10.1038/s41377-020-00352-1DOI Listing
June 2020

LEAFY COTYLEDON1 expression in the endosperm enables embryo maturation in Arabidopsis.

Nat Commun 2021 06 25;12(1):3963. Epub 2021 Jun 25.

London Research and Development Centre, Agriculture and Agri-Food Canada, London, ON, Canada.

The endosperm provides nutrients and growth regulators to the embryo during seed development. LEAFY COTYLEDON1 (LEC1) has long been known to be essential for embryo maturation. LEC1 is expressed in both the embryo and the endosperm; however, the functional relevance of the endosperm-expressed LEC1 for seed development is unclear. Here, we provide genetic and transgenic evidence demonstrating that endosperm-expressed LEC1 is necessary and sufficient for embryo maturation. We show that endosperm-synthesized LEC1 is capable of orchestrating full seed maturation in the absence of embryo-expressed LEC1. Inversely, without LEC1 expression in the endosperm, embryo development arrests even in the presence of functional LEC1 alleles in the embryo. We further reveal that LEC1 expression in the endosperm begins at the zygote stage and the LEC1 protein is then trafficked to the embryo to activate processes of seed maturation. Our findings thus establish a key role for endosperm in regulating embryo development.
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http://dx.doi.org/10.1038/s41467-021-24234-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233312PMC
June 2021

Mist1 Inhibits Epithelial-Mesenchymal Transition in Gastric Adenocarcinoma via Downregulating the Wnt/β-catenin Pathway.

J Cancer 2021 1;12(15):4574-4584. Epub 2021 Jun 1.

Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.

As a secretory cell transcription factor, muscle intestine stomach expression 1 (Mist1) is associated with serous secretory cell development and gastric chief cell maturation. Here, we focus on the function of Mist1 in gastric adenocarcinoma carcinogenesis. Based on clinical data and a mouse model of gastric cancer, we found that Mist1 expression was reduced in gastric cancer. Then, we overexpressed Mist1 using a lentivirus system and found that overexpression of Mist1 could inhibit gastric cancer cell proliferation, migration and invasion Additionally, , we assessed the function of Mist1 in a gastric cancer xenograft model and distant pulmonary metastasis model. Overexpression of Mist1 decreased tumour growth and distant metastasis , suggesting that Mist1 acts as a tumour suppressor in gastric carcinogenesis. Furthermore, Mist1 overexpression inhibited epithelial-mesenchymal transition (EMT) in gastric cancer by suppressing β-catenin transcription activity and then the Wingless and INT-1 (Wnt)/β-catenin signalling pathway, which could be reversed by a Wnt/β-catenin-specific agonist. In conclusion, this study indicated that overexpression of Mist1 could reverse EMT in gastric carcinogenesis by inhibiting the Wnt/β-catenin signalling pathway and that Mist1 might be a novel marker for early gastric cancer screening.
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http://dx.doi.org/10.7150/jca.59138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210560PMC
June 2021

Older Adults' Subjective Cognitive Decline Correlated with Subjective but Not Objective Sleep: A Mediator Role of Depression.

Int J Aging Hum Dev 2021 Jun 14:914150211024186. Epub 2021 Jun 14.

26463 Faculty of Psychology, Southwest University, Chongqing, China.

This study examined the relationship between older adults' subjective versus objective sleep and subjective cognitive decline (SCD), and explored the role of depression on this association. One hundred and four community-dwelling older adults underwent a week of actigraphic sleep monitoring, and completed a series of neuropsychological screeners. Older adults'SCD score was positively correlated with subjective insomnia, but not with objective sleep parameters. Further mediation modeling revealed that older adults'depression mediated the association between subjective insomnia and SCD. Subjective sleep, rather than objective sleep, may be a more sensitive indicator for older adults' SCD, with depression symptoms appearing to account for most of the variance. These findings extend our perspective on the relationship between sleep disruption and cognitive decline, and highlight the necessity of early targeted interventions on sleep to reduce the risk of cognitive impairment in the elderly with SCD.
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http://dx.doi.org/10.1177/00914150211024186DOI Listing
June 2021

Deep Adaptive Blending Network for 3D Magnetic Resonance Image Denoising.

IEEE J Biomed Health Inform 2021 Jun 8;PP. Epub 2021 Jun 8.

The visual quality of magnetic resonance images (MRIs) is crucial for clinical diagnosis and scientific research. The main source of quality degradation is the noise generated during MRI acquisition. Although denoising MRI by deep learning methods shows great superiority compared with traditional methods, the deep learning methods reported to date in the literature cannot simultaneously leverage long-range and hierarchical information, and cannot adequately utilize the similarity in 3D MRI. In this paper, we address the two issues by proposing a deep adaptive blending network (DABN) characterized by a large receptive field residual dense block and an adaptive blending method. We first propose the large receptive field residual dense block that can capture long-range information and fuse hierarchical features simultaneously. Then we propose the adaptive blending method that produces denoised pixels by adaptively filtering 3D MRI, which explicitly utilizes the similarity in 3D MRI. Residual is also considered as a compensating item after adaptive filtering. The blending adaptive filters and residual are predicted by a network consisting of several large receptive field residual dense blocks. Experimental results show that the proposed DABN outperforms state-of-the-art denoising methods in both clinical and simulated MRI data.
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http://dx.doi.org/10.1109/JBHI.2021.3087407DOI Listing
June 2021

Discovery of 1,5-Dihydro-4-imidazol-4-one Derivatives as Potent, Selective Antagonists of CXC Chemokine Receptor 2.

ACS Med Chem Lett 2021 May 8;12(5):836-845. Epub 2021 Apr 8.

Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, P.R. China.

CXC chemokine receptors 1 (CXCR1) and 2 (CXCR2) have been demonstrated to have critical roles in cancer metastasis. Because they share high homology sequences, it is still unclear how to design selective CXCR1 or CXCR2 antagonists. Based on a pharmacophore model we built, compound bearing a 1,5-dihydro-4-imidazol-4-one scaffold was identified as a selective CXCR2 antagonist with a low CXCR1 antagonism preference. Further optimization and structure-activity relationship studies led to compound that overcame the disadvantages of compound and performed with higher selectivity. It showed excellent oral bioavailability and in vitro anticancer metastasis activity. Further dynamic simulation of the molecular protein complex showed that the amino acid residue K320 of CXCR2 contributed most to the selectivity of . This study provides important clues for the design of new CXCR2 selective antagonists, and can be a molecular tool for investigating the difference in the biological function of CXCR1 and CXCR2.
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http://dx.doi.org/10.1021/acsmedchemlett.1c00113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155261PMC
May 2021

Metabolic reprogramming of terminally exhausted CD8 T cells by IL-10 enhances anti-tumor immunity.

Nat Immunol 2021 06 24;22(6):746-756. Epub 2021 May 24.

Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

T cell exhaustion presents one of the major hurdles to cancer immunotherapy. Among exhausted CD8 tumor-infiltrating lymphocytes, the terminally exhausted subset contributes directly to tumor cell killing owing to its cytotoxic effector function. However, this subset does not respond to immune checkpoint blockades and is difficult to be reinvigorated with restored proliferative capacity. Here, we show that a half-life-extended interleukin-10-Fc fusion protein directly and potently enhanced expansion and effector function of terminally exhausted CD8 tumor-infiltrating lymphocytes by promoting oxidative phosphorylation, a process that was independent of the progenitor exhausted T cells. Interleukin-10-Fc was a safe and highly efficient metabolic intervention that synergized with adoptive T cell transfer immunotherapy, leading to eradication of established solid tumors and durable cures in the majority of treated mice. These findings show that metabolic reprogramming by upregulating mitochondrial pyruvate carrier-dependent oxidative phosphorylation can revitalize terminally exhausted T cells and enhance the response to cancer immunotherapy.
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http://dx.doi.org/10.1038/s41590-021-00940-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610876PMC
June 2021

FRET-Based Probe for High-Throughput DNA Intercalator Drug Discovery and Imaging.

ACS Sens 2021 06 24;6(6):2233-2240. Epub 2021 May 24.

Physics Program, New York University Abu Dhabi, Abu Dhabi 129188, United Arab Emirates.

Molecules that bind DNA by intercalating its bases remain among the most potent cancer therapies and antimicrobials due to their interference with DNA-processing proteins. To accelerate the discovery of novel intercalating drugs, we designed a fluorescence resonance energy transfer (FRET)-based probe that reports on DNA intercalation, allowing rapid and sensitive screening of chemical libraries in a high-throughput format. We demonstrate that the method correctly identifies known DNA intercalators in approved drug libraries and discover previously unreported intercalating compounds. When introduced in cells, the oligonucleotide-based probe rapidly distributes in the nucleus, allowing direct imaging of the dynamics of drug entry and its interaction with DNA in its native environment. This enabled us to directly correlate the potency of intercalators in killing cultured cancer cells with the ability of the drug to penetrate the cell membrane. The combined capability of the single probe to identify intercalators and follow their function can play a valuable role in accelerating the discovery of novel DNA-intercalating drugs or repurposing approved ones.
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http://dx.doi.org/10.1021/acssensors.1c00167DOI Listing
June 2021

Generalized Pancharatnam-Berry Phase in Rotationally Symmetric Meta-Atoms.

Phys Rev Lett 2021 May;126(18):183902

State Key Laboratory of Optical Technologies on Nano-Fabrication and Micro-Engineering, Institute of Optics and Electronics, Chinese Academy of Sciences, Chengdu 610209, China.

Pancharatnam-Berry geometric phase has attracted enormous interest in subwavelength optics and electromagnetics during the past several decades. Traditional theory predicts that the geometric phase is equal to twice the rotation angle of anisotropic elements. Here, we show that high-order geometric phases equal to multiple times the rotation angle could be achieved by meta-atoms with highfold rotational symmetries. As a proof of concept, the broadband angular spin Hall effect of light and optical vortices is experimentally demonstrated by using plasmonic metasurfaces consisting of space-variant nanoapertures with C2, C3, and C5 rotational symmetries. The results provide a fundamentally new understanding of the geometric phase as well as light-matter interaction in nanophotonics.
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http://dx.doi.org/10.1103/PhysRevLett.126.183902DOI Listing
May 2021

CircHIPK2 Contributes to DDP Resistance and Malignant Behaviors of DDP-Resistant Ovarian Cancer Cells Both in vitro and in vivo Through circHIPK2/miR-338-3p/CHTOP ceRNA Pathway.

Onco Targets Ther 2021 13;14:3151-3165. Epub 2021 May 13.

Department of Gynaecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang City, Liaoning Province, People's Republic of China.

Background: Cisplatin (DDP) is standard-of-care and first-line management for ovarian cancer (OvCa). Circular RNA HIPK2 (circHIPK2) is abnormally upregulated in serum of OvCa patients. However, its role in DDP resistance remains unclear.

Methods: Expression of cirHIPK2, microRNA (miR)-338-3p and chromatin target of protein arginine methyltransferase (CHTOP) was detected by quantitative reverse transcription PCR and Western blotting. Functional experiments were performed using cell counting kit-8 assay, flow cytometry, transwell assays, Western blotting, and xenograft experiment. The interaction among cirHIPK2, miR-338-3p and CHTOP was confirmed by dual-luciferase reporter assay and RNA pull-down assay.

Results: Expression of circHIPK2 and CHTOP was upregulated, and miR-338-3p was downregulated in human DDP-resistant OvCa tumors and cells. Blocking circHIPK2 could promote apoptosis and suppress the 50% inhibitory concentration (IC50) of DDP, cell proliferation, cell cycle entrance, migration and invasion in SKOV3/DDP and A2780/DDP cells. Allied with that was decreased B cell lymphoma (Bcl)-2, matrix metalloproteinase 2 (MMP2) and MMP9 levels, and increased Bcl-2-associated X protein (Bax) level. Similarly, overexpression of miR-338-3p functioned suppressive role in SKOV3/DDP and A2780/DDP cells. MiR-338-3p was a target for circHIPK2, and CHTOP was targeted by miR-338-3p, whereas silencing miR-338-3p counteracted the role of circHIPK2 knockdown, and restoring CHTOP either cancelled miR-338-3p role. The growth of A2780/DDP cells in nude mice was restrained by silencing circHIPK2 under DDP treatment or not.

Conclusion: CircHIPK2 might be a tumor promoter in OvCa and was associated with DDP resistance. Silencing circHIPK2 might suppress DDP-resistant OvCa through regulating miR-338-3p/CHTOP axis.
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http://dx.doi.org/10.2147/OTT.S291823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128508PMC
May 2021

Social experiences with mental health service use among US adolescents.

J Ment Health 2021 May 19:1-9. Epub 2021 May 19.

Department of Health Policy and Management, School of Public Health, University of Maryland, College Park, MD, USA.

Background: Little is known about the associations of social experiences with mental health service use.

Aim: This study aimed to classify social experiences variables in the past year and examine the associations of selected variables in social experiences with mental health service use among US adolescents.

Methods: A total of 13,038 adolescents (aged 12 to 17), of which 2208 received mental health services, were from the 2018 National Survey on Drug Use and Health. Multivariate logistic regression (MLR) analysis was conducted.

Results: The overall prevalence of mental health service use was 16.1%. 44 variables on social experiences were grouped into 10 disjoint clusters and one variable from each cluster was selected for MLR analysis. Being female, African American, Hispanics, insured and having depression in the past year were associated with increased odds of mental health service use. Negative feelings about going to school, having a serious fight at school/work, active involvement in substance use help programs, knowledge of drug prevention, negative perceptions about the role of religious beliefs on life decisions were positively associated with mental health service use.

Conclusion: Mental health service use is associated with feelings about school and peers, perceptions about drug use, and involvement in activities.
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http://dx.doi.org/10.1080/09638237.2021.1922652DOI Listing
May 2021

APOBEC3B deletion polymorphism and lung cancer risk in the southern Chinese population.

Ann Transl Med 2021 Apr;9(8):656

Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China.

Background: Approximately 80-85% of lung cancer is the non-small cell lung cancer (NSCLC) subtype, which ranks as the leading cause of cancer deaths worldwide. (A3B) was reported to be a key source of mutations in NSCLC. However, the role of the A3B deletion polymorphism in the etiology of NSCLC has not been well-documented.

Methods: A case-control study with 317 NSCLC patients and 334 healthy controls was conducted to explore the association between the A3B deletion polymorphism and the risk of NSCLC. The unconditional logistic regression model was performed to calculate the odds ratio (OR) and the 95% confidence interval (CI), and the confounding factors were adjusted, including age, gender, and smoking status, to estimate the risk. An analysis of gene-environment interactions was performed using multifactor dimensionality reduction (MDR) software.

Results: We found that the del/del genotype of A3B deletion significantly increased NSCLC risk. Compared with individuals carrying the ins/ins genotype of A3B deletion, individuals with the del/del genotype had a 2.36 times increased risk of developing NSCLC after adjusting for confounding factors (OR =2.71, 95% CI: 1.67-4.42, P<0.001). A 3-factor gene-environment (A3B deletion, gender, and smoking) interaction model was found for NSCLC (OR =4.407, 95% CI: 1.174-16.549, P=0.028).

Conclusions: We propose that the A3B deletion polymorphism can increase the risk of developing NSCLC, and their interactions with gender and smoking may contribute to the risk of NSCLC in the southern Chinese population.
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http://dx.doi.org/10.21037/atm-21-989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105993PMC
April 2021

Enhanced emission from a single quantum dot in a microdisk at a deterministic diabolical point.

Opt Express 2021 May;29(10):14231-14244

We report on controllable cavity modes by controlling the backscattering by two identical scatterers. Periodic changes of the backscattering coupling between two degenerate cavity modes are observed with the changing angle between two scatterers and elucidated by a theoretical model using two-mode approximation and numerical simulations. The periodically appearing single-peak cavity modes indicate mode degeneracy at diabolical points. Interactions between single quantum dots and cavity modes are then investigated. Enhanced emission of a quantum dot with a six-fold intensity increase is obtained in a microdisk at a diabolical point. This method to control cavity modes allows large-scale integration, high reproducibility and flexible design of the size, the location, the quantity and the shape for scatterers, which can be applied for integrated photonic structures with scatterer-modified light-matter interaction.
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http://dx.doi.org/10.1364/OE.419740DOI Listing
May 2021

Epidemiological trends of maternal hypertensive disorders of pregnancy at the global, regional, and national levels: a population-based study.

BMC Pregnancy Childbirth 2021 May 8;21(1):364. Epub 2021 May 8.

Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, China.

Background: Relevant studies focusing on epidemiological of profiles hypertensive disorders of pregnancy from global data that report the cause-specific prevalence and trends of hypertensive disorders of pregnancy at global, regional and national levels from 1990 to 2019 by age and sociodemographic index are still limited.

Methods: For hypertensive disorders of pregnancy, point prevalence, annual incidence, and years lived with disability numbers and age standardized rates per 100,000 population were compared at regional and national levels by age and sociodemographic index using data from the global Burden of Disease 2019 Study, covering populations from 204 countries and territories. Estimates are reported with uncertainty intervals to exhibit the changing trends during a specific period.

Results: The incidence of hypertensive disorders of pregnancy increased from 16.30 million to 18.08 million globally, with a total increase of 10.92 % from 1990 to 2019. The age-standardized incidence rate decreased, with an estimated annual percent change of -0.68 (95 % confidence interval [CI] -0.49 to -0.86). The number of deaths due to hypertensive disorders of pregnancy was approximately 27.83 thousand in 2019, representing a 30.05 % decrease from 1990. Based on the incidence and prevalence, the number of deaths and years lived with disability were highest in the group aged 25-29 years, followed by the groups aged 30-34 and 20-24 years, while the lowest estimated incidence rate was observed in the group aged 25-29 years and higher incidence rates were observed in the youngest and oldest groups. Positive associations between incidence rates and the sociodemographic index and human development index were found for all countries and regions in 2019. Age-standardized incidence rates were higher in countries/regions with lower sociodemographic indices and human development indices.

Conclusions: Our study provides a comprehensive overview of the global burden of hypertensive disorders of pregnancy. The death and incidence rates are decreasing in most countries and all regions except for those with low sociodemographic and human development indexes. This difference is mainly due to the increasing attention to prenatal examinations and health education. Further investigations should focus on forecasting the global disease burden of specific hypertensive disorders of pregnancy and modifiable risk factors.
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http://dx.doi.org/10.1186/s12884-021-03809-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106862PMC
May 2021

Open Versus Endoscopic Osteotomy of Posterosuperior Calcaneal Tuberosity for Haglund Syndrome: A Retrospective Cohort Study.

Orthop J Sports Med 2021 Apr 19;9(4):23259671211001055. Epub 2021 Apr 19.

Institute of Sports Medicine, Beijing Key Laboratory of Sports Injury, Peking University Third Hospital, Beijing, People's Republic of China.

Background: Although endoscopic calcaneoplasty and retrocalcaneal debridement have been extensively applied to treat Haglund syndrome, evidence of the value of the endoscopic procedure remains to be fully established.

Purpose/hypothesis: The purpose of this study was to compare the postoperative outcomes and the amount of osteotomy between open and endoscopic surgery for the treatment of Haglund syndrome. It was hypothesized that endoscopic calcaneoplasty would lead to higher patient satisfaction and lower complication rates compared with open surgical techniques.

Study Design: Cohort study; Level of evidence, 3.

Methods: The following postoperative outcomes were compared between the open surgery group (n = 20) and the endoscopic surgery group (n = 27): visual analog scale for pain, American Orthopaedic Foot & Ankle Society ankle-hindfoot scale, Foot Function Index, Tegner score, Ankle Activity Score, and 36-Item Short Form Health Survey; postoperative complications; and duration of surgery. To determine the extent of resection, the authors compared the calcaneal height ratio, calcaneal resection ratio, calcaneal resection angle, pitch line, and Haglund deformity height between groups. The learning curve for endoscopic calcaneoplasty was also calculated.

Results: There were no significant differences between the open and endoscopic groups on any outcome score. Two patients in the open group reported temporary paresthesia around the incisional site, indicating sural nerve injuries; no complication was reported in the endoscopy group. None of the parameters for extent of resection were statistically significant between the groups. The duration of surgery was 44.90 ± 10.52 and 65.39 ± 11.12 minutes in the open and endoscopy groups, respectively ( = .001). Regarding the learning curve for endoscopic calcaneoplasty (6 surgeons; 27 follow-up patients; 9 patients lost to follow-up), the duration of surgery reached a steady point of 55.68 ± 4.19 minutes after the fourth operation.

Conclusion: The results of this study indicated that the endoscopy procedure was as effective as the open procedure. The endoscopic procedure required significantly more time than the open procedure, and the duration of the endoscopic procedure was shortened only after the fourth operation, suggesting that it requires high technical skills and familiarity with the anatomic relationships.
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http://dx.doi.org/10.1177/23259671211001055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058802PMC
April 2021

Reversed-engineered human alveolar lung-on-a-chip model.

Proc Natl Acad Sci U S A 2021 05;118(19)

Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139;

Here, we present a physiologically relevant model of the human pulmonary alveoli. This alveolar lung-on-a-chip platform is composed of a three-dimensional porous hydrogel made of gelatin methacryloyl with an inverse opal structure, bonded to a compartmentalized polydimethylsiloxane chip. The inverse opal hydrogel structure features well-defined, interconnected pores with high similarity to human alveolar sacs. By populating the sacs with primary human alveolar epithelial cells, functional epithelial monolayers are readily formed. Cyclic strain is integrated into the device to allow biomimetic breathing events of the alveolar lung, which, in addition, makes it possible to investigate pathological effects such as those incurred by cigarette smoking and severe acute respiratory syndrome coronavirus 2 pseudoviral infection. Our study demonstrates a unique method for reconstitution of the functional human pulmonary alveoli in vitro, which is anticipated to pave the way for investigating relevant physiological and pathological events in the human distal lung.
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http://dx.doi.org/10.1073/pnas.2016146118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126776PMC
May 2021

Sentence predictability modulates cortical response to phonetic ambiguity.

Brain Lang 2021 Jul 28;218:104959. Epub 2021 Apr 28.

Department of Speech, Language, and Hearing Sciences, University of Connecticut, Storrs, Mansfield, CT 06269, USA; Department of Psychological Sciences, University of Connecticut, Storrs, Mansfield, CT 06269, USA. Electronic address:

Phonetic categories have undefined edges, such that individual tokens that belong to different speech sound categories may occupy the same region in acoustic space. In continuous speech, there are multiple sources of top-down information (e.g., lexical, semantic) that help to resolve the identity of an ambiguous phoneme. Of interest is how these top-down constraints interact with ambiguity at the phonetic level. In the current fMRI study, participants passively listened to sentences that varied in semantic predictability and in the amount of naturally-occurring phonetic competition. The left middle frontal gyrus, angular gyrus, and anterior inferior frontal gyrus were sensitive to both semantic predictability and the degree of phonetic competition. Notably, greater phonetic competition within non-predictive contexts resulted in a negatively-graded neural response. We suggest that uncertainty at the phonetic-acoustic level interacts with uncertainty at the semantic level-perhaps due to a failure of the network to construct a coherent meaning.
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http://dx.doi.org/10.1016/j.bandl.2021.104959DOI Listing
July 2021

Expression Analysis of MIST1 and EMT Markers in Primary Tumor Samples Points to MIST1 as a Biomarker of Cervical Cancer.

Int J Gen Med 2021 14;14:1293-1300. Epub 2021 Apr 14.

Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, People's Republic of China.

Background: Mist1 is a basic transcription factor, which plays an important role in the development of multiple organs, and may also regulate tumor progression by mediating epithelial-mesenchymal transformation. However, there is lack of research on its role of squamous cell carcinoma, especially in cervical squamous cell carcinoma.

Methods: Bioinformatic methods were used to analyze gene expression, correlation, and patient survival according to the TCGA database. Thirty pairs of cancer tissues and distal cancer tissues from cervical cancer patients who received radical surgery were enrolled in the study. The expression of Mist1 was analyzed using Western blot. Furthermore, the potential associations among Mist1 expression, EMT biomarkers and various clinicopathological characteristics were investigated. All statistical tests employed in this study were two-sided, and values <0.05 were deemed statistically significant.

Results: Overall survival data were obtained from TCGA-CESC dataset, containing 3 control samples and 305 tumor samples. The expression of Mist1 was significantly higher in primary tumor than in normal tissues (<0.001). The samples were divided into a low Mist1 expression group (n=144) and a high Mist1 expression group (n=146) according to the median expression level. Kaplan-Meier survival analysis revealed that high expression of Mist1 was significantly correlated with poor overall survival (=0.032). We further explored the relationships between Mist1 and EMT. Among the 30 primary cervical cancer specimens investigated, the difference in Mist1 expressed statuses between cervical cancer tissues and distal noncancerous cervical tissues was significant (=0.001). And the epithelial cell marker E-cadherin was downregulated in Mist1 overexpressed cervical cancer cells; however, the mesenchymal marker N-Cadherin and Twist was upregulated.

Conclusion: Our study found that Mist1 seemed to play the role of oncogene in cervical squamous cell carcinoma and could be a potential biomarker.
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http://dx.doi.org/10.2147/IJGM.S307367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055369PMC
April 2021

Comparison of diagnosis of cracked tooth using contrast-enhanced CBCT and micro-CT.

Dentomaxillofac Radiol 2021 Apr 20:20210003. Epub 2021 Apr 20.

Department of Dentomaxillofacial Radiology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.

Objectives: To evaluate the diagnostic accuracy using sodium iodide (NaI) and dimethyl sulfoxide (DMSO) as contrast agent in cone beam computed tomography (CBCT) scanning, and compare this with micro-CT.

Methods: 18 teeth were cracked artificially by soaking them cyclically in liquid nitrogen and hot water. After pre-treatment with artificial saliva, the teeth were scanned in four modes: CBCT routine scanning without contrast agent (RS); CBCT with meglumine diatrizoate (MD) as contrast agent (ES1); CBCT with NaI + DMSO as contrast agent (ES2); and micro-CT (mCT). The number of crack lines was evaluated in all four modes. Depth of crack lines and number of cracks presented from the occlusal surface to the pulp cavity (Np) in ES2 and micro-CT images were evaluated.

Results: There were 63 crack lines in all 18 teeth. 45 crack lines were visible on ES2 images as against four on the RS and ES1 images (0.05) and 37 on micro-CT images (0.05). Further, 34 crack lines could be observed on both ES2 and micro-CT images, and the average depth presented on ES2 images was 4.56 ± 0.88 mm and 3.89 ± 1.08 mm on micro-CT images (0.05). More crack lines could be detected from the occlusal surface to the pulp cavity on ES2 images than on micro-CT images (22 11).

Conclusion: CBCT with NaI +DMSO as the contrast agent was equivalent to micro-CT for number of crack lines and better for depth of crack lines. NaI + DMSO could be a potential CBCT contrast agent to improve diagnostic accuracy for cracked tooth.
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http://dx.doi.org/10.1259/dmfr.20210003DOI Listing
April 2021

Correlations between tumor mutation burden and immune infiltrates and their prognostic value in pancreatic cancer by bioinformatic analysis.

Life Sci 2021 Jul 16;277:119505. Epub 2021 Apr 16.

Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address:

Purpose: We aimed to investigate the patterns and prognostic roles of tumor mutation burden and immune microenvironment in pancreatic cancer.

Methods: The somatic mutation data, transcriptome profiles and clinical information were downloaded from the Cancer Genome Atlas database. Gene expression difference, Gene ontology, KEGG, gene set enrichment analyses and "CIBERSORT" algorithm were performed to screen differentially expressed genes, enriched functions or pathways and immune infiltrates differences between high and low TMB groups. Single sample gene set enrichment and unsupervised consensus clustering analyses were used for immunity grouping. Immune cell infiltration and expressions of HLA and checkpoint genes were investigated. Finally, a nomogram model integrating TMB and immune infiltration was established.

Results: A total of 608 differentially expressed genes were identified between high and low TMB groups, KEGG base excision repair and DNA replication pathways were enriched in high TMB group. Infiltration levels of M0 macrophages were higher and dendritic resting cells were lower in high TMB group. The risk model based on TMB-related immune genes, FAM19A2 and SLC22A17 was established and high risk scores indicated poorer prognosis. The expressions of HLA genes and immune checkpoint genes were higher in high immunity group. The nomogram showed remarkable ability for individualized survival estimation with good AUC values (0.794 and 0.800, respectively) for 3- and 5-year survival rates prediction.

Conclusions: The characteristics of tumor mutation burden and immune infiltration in pancreatic cancer provide new insights into the tumor microenvironment, immunotherapies and a novel prognostic nomogram model for pancreatic cancer patients.
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http://dx.doi.org/10.1016/j.lfs.2021.119505DOI Listing
July 2021

Research on the Interaction Mechanism Between α Mino-Phosphonate Derivative Q-R and Harpin-Binding Protein 1 in Tobacco () Plants.

Front Microbiol 2021 23;12:621875. Epub 2021 Mar 23.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang, China.

Amino-phosphonate derivative R-diphenyl-1-(4-methylbenzothiazole-2-amino)-1-(thiphene-2-yl)-methylphosphonate (Q-R) has a high protective anti-tobacco mosaic virus (TMV) activity. However, the mechanism responsible for Q-R's effect on TMV infection is largely unknown. Here, we studied the expression levels of harpin-binding protein 1 (HrBP1) and pathogenesis-related protein-1a (PR-1a) in TMV-infected tobacco plants by using reverse transcription quantitative real-time PCR. Then, we verified the interactions between Q-R and the HrBP1 protein from using isothermal titration calorimetry and studied the Q-R-associated assembly of HrBP1 using size-exclusion chromatography. The results showed that the expression levels of HrBP1 and PR-1a genes were significantly increased by Q-R at the transcriptional level in TMV-infected tobacco plants, and the -expressed HrBP1 protein was assembled into oligomers by Q-R via binding to HrBP1 with a dissociation constant of 1.19 μM. We, therefore, concluded that Q-R activated the HrBP1 and PR-1a genes and enhanced the ability of HrBP1 to assemble in tobacco plants.
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http://dx.doi.org/10.3389/fmicb.2021.621875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044911PMC
March 2021

Suppressing the Voltage Decay Based on a Distinct Stacking Sequence of Oxygen Atoms for Li-Rich Cathode Materials.

ACS Appl Mater Interfaces 2021 Apr 7;13(15):17639-17648. Epub 2021 Apr 7.

National Base for International Science & Technology Cooperation, National Local Joint Engineering Laboratory for Key Materials of New Energy Storage Battery, Hunan Province Key Laboratory of Electrochemical Energy Storage & Conversion, School of Chemistry, Xiangtan University, Xiangtan 411105, China.

Li-rich cathode materials possess a much higher theoretical energy density than all intercalated cathode materials currently reported and thus are considered as the most promising candidate for next-generation high-energy density Li-ion batteries. However, the rapid voltage decay and the irreversible phase transition of O3-type Li-rich cathode materials often lessen their actual energy density and limit their practical applications, and thus, effectively suppressing the voltage decay of Li-rich cathodes becomes the hotspot of the current research. Herein, the F-doped O2-type Li-rich cathode materials LiMnNiCoOF (F-O2-LRO) are designed and prepared based on the P2-type sodium-ion cathode materials NaLi(MnNiCo)O (Na-LRO) by ion exchange. It has been found that the as-prepared F-O2-LRO exhibits excellent electrochemical performance, for example, a high discharge specific capacity of 280 mA h g at 0.1 C with an initial Coulombic efficiency of 94.4%, which is obviously higher than the original LRO (77.2%). After 100 cycles, the F-O2-LRO cathode can still maintain a high capacity retention of 95% at a rate of 1 C, while the capacity retention of the original LRO is only 69.1% at the same current rate. Furthermore, the voltage difference (Δ) of F-O2-LRO before and after cycling is only 0.268 V after 100 cycles at 1 C, which is less than that of the LRO cathode (0.681 V), indicating much lower polarization. Besides, even at a high current rate of 5 C, F-O2-LRO still displays a satisfactory discharge capacity of 210 mA h g with a capacity retention of 90.1% after 100 cycles. Therefore, this work put forward a new strategy for the development and industrial application of Li-rich cathode materials in high-energy Li-ion batteries.
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http://dx.doi.org/10.1021/acsami.1c02424DOI Listing
April 2021

Improving deformable image registration with point metric and masking technique for postoperative breast cancer radiotherapy.

Quant Imaging Med Surg 2021 Apr;11(4):1196-1208

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Deformable image registration (DIR) is increasingly used for target volume definition in radiotherapy. However, this method is challenging for postoperative breast cancer patients due to the large deformations and non-correspondence caused by tumor resection and clip insertion. In this study, an improved B-splines based DIR method was developed to address this issue for higher registration accuracy.

Methods: The conventional B-splines based DIR method was improved with the introduction of point metric and masking technique. The point metric minimizes the distance between 2 point sets with known correspondence for regularization of intensity-based B-splines registration. The masking technique reduces the influence of non-corresponding regions in breast computed tomography (CT) images. Two sets of CT images before and after breast surgery were used for image registration. One set was the diagnostic CT image acquired before surgery, and another set was the planning CT image acquired after surgery for breast cancer radiotherapy. A total of 26 sets of CT images from 13 patients were collected retrospectively for the test. The improved DIR method's registration accuracy was evaluated by target registration error (TRE), the Jacobian determinant, and visual assessment.

Results: For soft tissue, the difference in the median TRE between the improved DIR method and the conventional DIR method was statistically significant (2.27 5.88, P<0.05). The Jacobian determinant of the deformation field was positive for all patients. For visual assessment, the improved DIR method with point metric achieved better matching for soft tissue.

Conclusions: The improved DIR method's registration accuracy was higher than the conventional DIR method based on the preliminary results. With point metric and masking technique, the influence of large deformations and non-correspondence on registration between pre- and post-operative CT images can be effectively reduced. Therefore, this method provides a feasible way for target volume definition in postoperative breast cancer radiotherapy treatment planning.
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http://dx.doi.org/10.21037/qims-20-705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930685PMC
April 2021

The Two Formyl Peptide Receptors Differently Regulate GPR84-Mediated Neutrophil NADPH Oxidase Activity.

J Innate Immun 2021 Mar 31:1-15. Epub 2021 Mar 31.

Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.

Neutrophils express the two formyl peptide receptors (FPR1 and FPR2) and the medium-chain fatty acid receptor GPR84. The FPRs are known to define a hierarchy among neutrophil G protein-coupled receptors (GPCRs), that is, the activated FPRs can either suppress or amplify GPCR responses. In this study, we investigated the position of GPR84 in the FPR-defined hierarchy regarding the activation of neutrophil nicotine adenine dinucleotide phosphate (NADPH) oxidase, an enzyme system designed to generate reactive oxygen species (ROS), which are important regulators in cell signaling and immune regulation. When resting neutrophils were activated by GPR84 agonists, a modest ROS release was induced. However, vast amounts of ROS were induced by these GPR84 agonists in FPR2-desensitized neutrophils, and the response was inhibited not only by a GPR84-specific antagonist but also by an FPR2-specific antagonist. This suggests that the amplified GPR84 agonist response is achieved through a reactivation of desensitized FPR2s. In addition, the GPR84-mediated FPR2 reactivation was independent of β-arrestin recruitment and sensitive to a protein phosphatase inhibitor. In contrast to FPR2-desensitized cells, FPR1 desensitization primarily resulted in a suppressed GPR84 agonist-induced ROS response, indicating a receptor hierarchical desensitization of GPR84 by FPR1-generated signals. In summary, our data show that the two FPRs in human neutrophils control the NADPH oxidase activity with concomitant ROS production by communicating with GPR84 through different mechanisms. While FPR1 desensitizes GPR84 and by that suppresses the release of ROS induced by GPR84 agonists, amplified ROS release is achieved by GPR84 agonists through reactivation of the desensitized FPR2.
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http://dx.doi.org/10.1159/000514887DOI Listing
March 2021
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