Publications by authors named "Xin Wang"

8,128 Publications

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Self-Standing combined covalent-organic-framework membranes for subzero conductivity assisted by ionic liquids.

J Colloid Interface Sci 2021 Apr 30;599:595-602. Epub 2021 Apr 30.

College of Environmental and Chemical Engineering, Xi'an Polytechnic University, Xi'an 710048, PR China. Electronic address:

The development of proton-conducting materials in cold regions is still at the initial stage due to the challenge in breaking the subzero temperature limit, especially in covalent organic frameworks (COFs). Herein, we fabricated a series of proton-conductive COFs as self-standing, highly flexible combined membranes (ssc-COFMs) composed of a processable TpBD-Me and a conductive Tp-TG, in-situ encapsulated proton-conducting ionic liquids (PCILs) as additional proton sources into backbones. Compositions and microstructures of ssc-COFMs are monitored by XRD, FTIR, nitrogen adsorption and elemental analysis. Comparison to other porous organic conductors, a great advance propelled renders the combined COF membranes to have a high protonic conductivities at medium and subzero temperatures (243 to 353 K), owing to the resultant multifaceted synergistic effect of multiple proton units. Specifically, the proton conductivities of the ssc-COFMs loaded with -SOH functionalized PCILs reaches 2.87 × 10 S cm (~58% RH) and 9.93 × 10 S cm (~98% RH) at 243 K, together with 6.84 × 10 S·cm under 353 K and ~ 98% RH.
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http://dx.doi.org/10.1016/j.jcis.2021.04.130DOI Listing
April 2021

Optimization and application of high-throughput supported liquid extraction for simultaneous determination of carotenoids and fat-soluble vitamins in serum.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Mar 24;1173:122672. Epub 2021 Mar 24.

School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shanxi 710061, PR China. Electronic address:

The demand for analysis of carotenoids (CAR) and fat-soluble vitamins (FSV) is continuously expanding, but currently used sample preparation methods either require complicated extraction procedure or large sample volume, let alone the reliability of the results. This study aimed to develop a fast, high-efficient, and high-throughput method based on supported liquid extraction (SLE) for the simultaneous extraction of FSV and CAR from human serum before using high-performance liquid chromatography-diode array detector (HPLC-DAD) analysis. The optimization of SLE parameters was achieved through response surface methodology (RSM) based on the Box-Behnken design (BBD) and included serum-water-extraction solvent ratio and eluent volume. Under optimal conditions, the proposed method gives acceptable limits of detection (LOD) (0.005-0.3 μg/mL), good recovery (89.6-110.9%) as well as relative standard deviation (RSD) of less than 10.1% by consuming lower serum sample (100 μL) and less sample preparation time (2 min per sample). Compared with liquid-phase extraction (LLE), the SLE delivers rapid extraction with higher recovery, better reproducibility, and lower matrix effect for CAR and FSV analysis. The method has been successfully applied to quantify CAR and FSV levels in serum of healthy individuals and age-related macular degeneration (AMD) patients, demonstrating the feasibility of the proposed method for epidemiology and routine applications.
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http://dx.doi.org/10.1016/j.jchromb.2021.122672DOI Listing
March 2021

Neuroprotective Effects of Fingolimod Supplement on the Retina and Optic Nerve in the Mouse Model of Experimental Autoimmune Encephalomyelitis.

Front Neurosci 2021 26;15:663541. Epub 2021 Apr 26.

Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Favorable effects exerted by long-term administration of fingolimod therapy in multiple sclerosis (MS) patients have been reported, but sporadic side effects, such as reversible macular edema, also have been recorded. The present study aimed to determine whether fingolimod therapy is beneficial to the visual system in experimental autoimmune encephalomyelitis (EAE) mice. A decrease in demyelination and axon loss in the optic nerve as well as cellular infiltration, especially the recruited macrophages, was observed in EAE with fingolimod treatment. Fingolimod administration diminished hypergliosis of macroglia, including astrocytes and Müller cells in the retina and optic nerve in EAE. Microglia were hyperactivated in the retina and optic nerve in the EAE mice compared to controls, which could be alleviated by fingolimod treatment. Moreover, apoptosis of retinal ganglion cells (RGC) and oligodendrocytes in the optic nerve was significantly reduced with fingolimod treatment compared to that in the untreated EAE mice. These results suggested that fingolimod exerts neuroprotective and anti-inflammatory effects on the retina and optic nerve in a mouse model of EAE. Considering the paradox of favorable and side effects of fingolimod on visual system, we speculate that side effects including macular oedema caused by fingolimod during MS treatment is tendency to be vasogenic rather than hypergliosis in optic nerve and retina which warrants further neuroophthalmological investigation.
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http://dx.doi.org/10.3389/fnins.2021.663541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107225PMC
April 2021

Neonatal screening and genotype-phenotype correlation of hyperphenylalaninemia in the Chinese population.

Orphanet J Rare Dis 2021 May 12;16(1):214. Epub 2021 May 12.

Genetic Medicine Center, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, 123 Tianfei St., Qinhuai District, Nanjing, 210004, People's Republic of China.

Background: Hyperphenylalaninemia (HPA) is the most common amino acid metabolic disease involving phenylalanine hydroxylase (PAH, OMIM*612,349) deficiency or coenzyme tetrahydrobiopterin (BH4) deficiency. Patients with severe HPA often have a difficult life. Early diagnosis of HPA before the development of symptoms is possible via neonatal screening, facilitating appropriate treatment and reducing mortality and disability rates. This study revealed the prevalence, mutational and phenotypic spectrum, and prognosis of HPA by neonatal screening from January 2001 to September 2020 in Nanjing, Jiangsu Province, China.

Methods: Through a retrospective analysis of the information available in the neonatal screening database, the clinical presentations, laboratory data, molecular characteristics and treatment follow-up data of HPA patients detected by neonatal screening were evaluated.

Results: We diagnosed 181 patients with HPA from 1 to 957 newborns, giving an incidence of 1:6873. Among these patients, 177 were identified as PAH deficient and four patients were BH4 deficient. The average current age of the patients was 6.38 years old. The most common mutations of PAH were c.728 C > A/ p.Arg243Gln (13.83 %), c.158G > A/ p.Arg53His (9.57 %), c.611 A > G/ p.Tyr204Cys (7.44 %), and c.721 C > T/ p.Arg241Cys (6.38 %).

Conclusions: This study revealed the prevalence, phenotype-genotype, and prognosis of HPA in China and contributes to the updating of PAHD data for China and worldwide. Our study not only expanded the spectrum of phenotypes and genotype but also provided a valuable tool for improved genetic counseling and management of future cases.
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http://dx.doi.org/10.1186/s13023-021-01846-wDOI Listing
May 2021

Assembly of fluorinated chromanones enantioselective tandem reaction.

Chem Commun (Camb) 2021 May;57(38):4722-4725

School of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, Chongqing 401331, P. R. China.

The enantioselective synthesis of fluorinated tricyclic chromanones with multiple vicinal stereogenic centers has been realized for the first time, through the tandem reaction between 2-fluorinated 1-(2-hydroxyaryl)-1,3-diketones and α,β-unsaturated aldehydes. In the presence of chiral amine, the organo-tandem reaction including catalytic Michael addition/cycloketalization/hemiacetalization and acylation sequence provided a wide range of fluorinated tricyclic chromanones with excellent outcomes (>30 examples, up to >99% ee and >19 : 1 d.r.). A plausible catalytic cycle and transition state are also provided for this tandem reaction to rationalize the observed sense of asymmetric induction.
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http://dx.doi.org/10.1039/d1cc01187aDOI Listing
May 2021

A Validation Study of the Rainbow Model of Integrated Care-Measurement Tool for Patients in China.

Int J Integr Care 2021 Apr 19;21(2). Epub 2021 Apr 19.

Department of Health Services Research, Care and Public Health Research Institute (CAPHRI), Faculty of Health, Medicine and Life Sciences, Maastricht University, The Netherlands.

Introduction: The original Rainbow Model of Integrated Care Measurement Tool (RMIC-MT) is based on the Rainbow Model of Integrated Care (RMIC), which provides a comprehensive theoretical framework for integrated care. The aim of this paper is to modify the original patient version of the RMIC-MT for the Chinese primary care context and validate its psychometric properties.

Methods: The translation and adaptation processes were performed in four steps, forward and back-translation, experts review and pre-testing. We conducted a cross-sectional study with 386 patients with diabetes attending one of 20 community health stations in the Nanshan district. We analyzed the distribution of responses to each item to study the psychometric sensitivity. Exploratory factor analysis with principal axis extraction method was used to assess the construct validity. Confirmation factor analysis was used to evaluate model fit of the modified version. Cronbach's alpha was used to ascertain the internal consistency reliability.

Results: During the translation and adaptation process, all 24 items were retained with some detailed modifications. No item was found to have psychometric sensitivity problems. Five factors (person-centeredness, clinical integration, professional integration, team-based coordination, organizational integration) with 15 items were determined by exploratory factor analysis, accounting for 53.51% of the total variance. Good internal consistency was achieved with each item correlated the highest on an assigned subscale and Cronbach's alpha score of 0.890. Moderately positive associations (r≥ 0.4, p<0.01) between the score of the scale and these correlations indicate good construct validity.

Conclusions: The results showed initial satisfactory psychometric properties for the validation of the Chinese RMIC-MT patient version. Its application in China will promote the development of people-centered integrated primary care. However, future studies with diverse samples crossing regions would be needed to test its psychometric properties for the various Chinese primary care contexts.
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http://dx.doi.org/10.5334/ijic.5603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064292PMC
April 2021

Phosphorylated Gβ is a directional cue during yeast gradient tracking.

Sci Signal 2021 May 11;14(682). Epub 2021 May 11.

Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.

Budding yeast cells interpret shallow pheromone gradients from cells of the opposite mating type, polarize their growth toward the pheromone source, and fuse at the chemotropic growth site. We previously proposed a deterministic, gradient-sensing model that explains how yeast cells switch from the intrinsically positioned default polarity site (DS) to the gradient-aligned chemotropic site (CS) at the plasma membrane. Because phosphorylation of the mating-specific Gβ subunit is thought to be important for this process, we developed a biosensor that bound to phosphorylated but not unphosphorylated Gβ and monitored its spatiotemporal dynamics to test key predictions of our gradient-sensing model. In mating cells, the biosensor colocalized with both Gβ and receptor reporters at the DS and then tracked with them to the CS. The biosensor concentrated on the leading side of the tracking Gβ and receptor peaks and was the first to arrive and stop tracking at the CS. Our data showed that the concentrated localization of phosphorylated Gβ correlated with the tracking direction and final position of the G protein and receptor, consistent with the idea that gradient-regulated phosphorylation and dephosphorylation of Gβ contributes to gradient sensing. Cells expressing a nonphosphorylatable mutant form of Gβ exhibited defects in gradient tracking, orientation toward mating partners, and mating efficiency.
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http://dx.doi.org/10.1126/scisignal.abf4710DOI Listing
May 2021

Molecular Dynamics Exploration of the Growth Mechanism of Hydroxyapatite Nanoparticles Regulated by Glutamic Acid.

J Phys Chem B 2021 May 11. Epub 2021 May 11.

College of Chemistry, MOE Key Laboratory of Green Chemistry and Technology, Sichuan University, Chengdu, Sichuan 610064, P. R. China.

Morphological control can enhance the performance of materials like hydroxyapatite (HAP), a well-known bioceramic with various morphologies, including spheres, rods, whiskers, needles, and plates. To obtain certain HAP morphologies, the crystal growth mechanisms at different planes should be investigated. Here, molecular dynamics was employed to understand the mechanism of HAP nanoparticle growth regulated by glutamic acid (Glu). Long-time dynamics simulations and free energy calculations were performed to explore the effect of Glu on calcium and phosphate ion precipitation on the HAP (100) and (001) faces. Without Glu, PO prefers binding to the HAP (100) surface, whereas with Glu, the (001) surface is preferred. This could partially explain why HAP changes from needle-like to plate-like with Glu addition in experiments. Our theoretical results indicate that Glu inhibits calcium and phosphate ion deposition on the crystal surfaces by occupying the calcium sites on the outermost layers. In addition, Glu has a strong concentration gradient effect on HAP deposition. At Glu concentrations of >80 mM, ion deposition was inhibited more on the (100) than on the (001) surface. Our results agree with experimental observations and afford insights into complicated HAP crystal growth mechanisms with foreign additives, which will aid in HAP synthesis with morphological control.
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http://dx.doi.org/10.1021/acs.jpcb.1c02447DOI Listing
May 2021

Aortic Dissection with Rare Anatomical Aortic Arch Variation Depicted by Computed Tomography Angiography.

Heart Surg Forum 2021 Apr 27;24(2):E407-E408. Epub 2021 Apr 27.

Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China.

Aortic dissection (AD) is a life-threatening disease, and endovascular repair by stent graft is an effective treatment. Surgery often fails for a variety of reasons, such as aortic arch variation. We present the case of a 27-year-old female with aortic dissection with a rare anatomical aortic arch variation caused by chest trauma. This patient recovered well after endovascular repair. This case report demonstrates endovascular repair can be applied to aortic dissection patients with rare anatomical aortic arch variation.
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http://dx.doi.org/10.1532/hsf.3619DOI Listing
April 2021

The physicochemical properties and stability of flaxseed oil emulsions: effects of emulsification methods and the ratio of soybean protein isolate to soy lecithi.

J Sci Food Agric 2021 May 10. Epub 2021 May 10.

School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.

Background: The properties and stability of emulsion were greatly relied on the emulsification method and emulsifier. In this study, different emulsification methods (high speed homogenization, ultrasonic treatment and their combination) were employed for the preparation of emulsions stabilized by soybean protein isolate (SPI) and soy lecithin (SLT) at three ratios. The microstructure, hydrodynamic average diameter, ζ-potential, creaming stability and low-field NMR relaxation behaviors of emulsions were investigated.

Results: The results indicated that the influence of emulsification method was closely related to the ratio of SPI/SLT. Overall, the SPI-SLT stabilized emulsion treated by ultrasound showed better stability and uniformity, while the combined treatment of high-speed homogenization and ultrasound was helpful to improve the uniformity and stability of SPI stabilized Pickering emulsion. However, the SLT stabilized emulsions all exhibited worse uniformity in terms of particle size distribution and polydispersity index.

Conclusion: These results will be helpful for selecting appropriate emulsification method and emulsifier to improve the stability of emulsions. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jsfa.11311DOI Listing
May 2021

Pulmonary arterial hypertension in a patient with hereditary hemorrhagic telangiectasia and family gene analysis: A case report.

World J Clin Cases 2021 May;9(13):3079-3089

Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China.

Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant genetic disease. Very few patients suffering from HHT present with associated pulmonary arterial hypertension (PAH), which may result in a poor prognosis. Here, we report a case of HHT with PAH. The patient's clinical manifestations and treatment as well as genetic analysis of family members are reviewed, in order to raise awareness of this multimorbidity.

Case Summary: A 45-year-old Chinese woman was admitted to the hospital to address a complaint of intermittent shortness of breath, which had lasted over the past 2 years. She also had a 30-year history of recurrent epistaxis and 5-year history of anemia. She reported that the shortness of breath had aggravated gradually over the 2 years. Physical examination discovered anemia and detected gallop rhythm in the precordium. Chest computerized tomography and cardiac ultrasound demonstrated PAH and hepatic arteriovenous malformation. The formal clinical diagnosis was HHT combined with PAH. The patient was treated with ambrisentan and her condition improved for a time. She died half a year after the diagnosis. Genetic testing revealed the patient and some family members to carry an activin A receptor-like type 1 mutation (c. 1232G>A, p. Arg411Gln); the family was thus identified as an HHT family.

Conclusion: We report a novel gene mutation (c. 1232G>A, p. Arg411Gln) in a Chinese HHT patient with PAH.
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http://dx.doi.org/10.12998/wjcc.v9.i13.3079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080754PMC
May 2021

Laryngeal myxoma: A case report.

World J Clin Cases 2021 Apr;9(12):2823-2829

Department of Otolaryngology, Head and Neck Surgery, Jilin University, Changchun 130000, Jilin Province, China.

Background: Myxomas are benign tumors of mesenchymal origin that rarely occur in the larynx.

Case Summary: We report a case of a laryngeal myxoma that presented as a right vocal cord mass in a 54-year-old man.

Conclusion: Laryngeal myxoma is a rare benign tumor in the larynx. It is difficult to distinguish glottis myxoma from vocal cord polyps on laryngoscopy. We recommend that otolaryngologists acquire a better understanding of this disease. If a laryngeal myxoma is suspected, dynamic laryngoscopy, acoustic voice analysis, and pathological biopsy should be performed.
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http://dx.doi.org/10.12998/wjcc.v9.i12.2823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058668PMC
April 2021

NEM-Tar: A Probabilistic Graphical Model for Cancer Regulatory Network Inference and Prioritization of Potential Therapeutic Targets From Multi-Omics Data.

Front Genet 2021 22;12:608042. Epub 2021 Apr 22.

Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.

Targeted therapy has been widely adopted as an effective treatment strategy to battle against cancer. However, cancers are not single disease entities, but comprising multiple molecularly distinct subtypes, and the heterogeneity nature prevents precise selection of patients for optimized therapy. Dissecting cancer subtype-specific signaling pathways is crucial to pinpointing dysregulated genes for the prioritization of novel therapeutic targets. Nested effects models (NEMs) are a group of graphical models that encode subset relations between observed downstream effects under perturbations to upstream signaling genes, providing a prototype for mapping the inner workings of the cell. In this study, we developed NEM-Tar, which extends the original NEMs to predict drug targets by incorporating causal information of (epi)genetic aberrations for signaling pathway inference. An information theory-based score, weighted information gain (WIG), was proposed to assess the impact of signaling genes on a specific downstream biological process of interest. Subsequently, we conducted simulation studies to compare three inference methods and found that the greedy hill-climbing algorithm demonstrated the highest accuracy and robustness to noise. Furthermore, two case studies were conducted using multi-omics data for colorectal cancer (CRC) and gastric cancer (GC) in the TCGA database. Using NEM-Tar, we inferred signaling networks driving the poor-prognosis subtypes of CRC and GC, respectively. Our model prioritized not only potential individual drug targets such as HER2, for which FDA-approved inhibitors are available but also the combinations of multiple targets potentially useful for the design of combination therapies.
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http://dx.doi.org/10.3389/fgene.2021.608042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100334PMC
April 2021

Traditional Chinese medicine prescription Guizhi Fuling Pills in the treatment of endometriosis.

Int J Med Sci 2021 16;18(11):2401-2408. Epub 2021 Apr 16.

College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, PR China.

Endometriosis (EMs) is recorded as in traditional Chinese medicine (TCM) books. Guizhi Fuling Pills (GFPs), a classic prescription for promoting blood circulation and removing blood stasis, is widely used for women's blood stasis diseases represented by . At present, it has been applied to treat EMs in clinical settings. In this review, we systematically summarized the active ingredients and pharmacological mechanism of five Chinese herbs contained in GFPs and clinical applications of GFPs. The potential pathways of GFPs in the treatment of EMs were explored through network pharmacology. The current researches results indicate that the mechanisms of GFPs in the treatment of EMs mainly include acesodyne, anti-inflammation and improvement of hemodynamics. The main active compounds that are responsible for pharmacological effects in five Chinese herbs are paeonol, pachymic acid, cinnamaldehyde, amygdaloside and Paeoniflorin. This review can lay the foundation and identify the research direction for the development of GFPs as a new drug therapy for the treatment of EMs.
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http://dx.doi.org/10.7150/ijms.55789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100639PMC
April 2021

Synaptic changes and the response of microglia in a light-induced photoreceptor degeneration model.

Mol Vis 2021 1;27:206-220. Epub 2021 May 1.

Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.

Purpose: To explore synaptic changes and the response of microglia in a light-induced photoreceptor degeneration model.

Methods: Sprague-Dawley rats were euthanized 1 h, 1 day, 3 days, 7 days, and 14 days after being exposed to intense blue light for 24 h. Hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining were used to evaluate changes in the outer nuclear layer (ONL). Transmission electron microscopy (TEM) was applied to observe the ultrastructural changes in the synapses between the photoreceptors and second-order neurons. Western blotting was conducted to evaluate specific proteins, including postsynaptic density-95 (PSD-95), metabotropic glutamate receptor 6 (mGluR6), synapsin I, and synaptophysin. Immunofluorescence of CD11b and PKC-α or mGluR6 was used to explore the spatial relationships between microglial processes and synaptic elements. Immunoelectron microscopy of PSD-95 was performed to further confirm its engulfment of synaptic materials.

Results: H&E and TUNEL staining showed that the thickness of the ONL decreased markedly, and the number of apoptotic photoreceptors peaked at day 1. TEM revealed darkened photoreceptor terminals and that ribbons of them were floating in the cytoplasm, coinciding with the downregulation of PSD-95 and mGluR6. Downstream synaptic protein synapsin I and synaptophysin exhibited upregulation in the inner plexiform layer. Activated microglia migrated to the outer retina, and their processes were found in close proximity to synapses in the outer plexiform layer under light and electron microscopy levels. Double immunostaining of CD11b and mGluR6 showed colocalization. PSD-95-immunoreactive electron-dense materials were observed inside the microglia suggesting engulfment of synaptic components.

Conclusions: The study showed that there are early synaptic impairment and late compensatory changes in downstream synapses in this photic injury model. Activated microglia touched and directly engulfed synaptic materials. Microglia may play a role or a partial role in synaptic changes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100860PMC
May 2021

Patient-Reported Outcomes for Cancer Patients with Hematological Malignancies Undergoing Chimeric Antigen Receptor T Cell Therapy: A Systematic Review.

Transplant Cell Ther 2021 May 7;27(5):390.e1-390.e7. Epub 2021 Jan 7.

Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address:

Databases were searched to identify studies published over the past 10 years that addressed the utility of patient-reported outcomes (PROs) in patients receiving chimeric antigen receptor (CAR) T cell therapy in patients with hematological malignancies. Among 280 records, three articles covering 206 patients were eligible. The data were prospectively collected at multiple time points. The compliance rates were 70% to 94%. There was an inverse relationship between fatigue and social function among adults. The quality of life (QoL) improvement and ability to complete PROs were linked to disease status. About 40% of adults reported at least some cognitive difficulties, with a detrimental impact on mental and physical health status. In adults, the most commonly reported cognitive impairment was memory difficulties. Depression was associated with cognitive difficulties. Younger adults were at higher risk of long-term poor mental health, anxiety, and depression. For pediatric and adolescent patients, emotional dysfunction improves over time. QoL status improved over time; yet, severe cytokine release syndrome and neurotoxicity caused delayed improvement. Information regarding whether the PROs were integrated into medical records and clinical guidelines is lacking. Utilizing PROs in patients on CAR T cell therapy seems feasible and informative. Studies utilizing larger sample sizes and using validated PRO tools at different time points remain unmet needs.
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http://dx.doi.org/10.1016/j.jtct.2021.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110951PMC
May 2021

Phthalates promote the invasion of hepatocellular carcinoma cells by enhancing the interaction between Pregnane X receptor and E26 transformation specific sequence 1.

Pharmacol Res 2021 May 6:105648. Epub 2021 May 6.

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, P.R. China. Electronic address:

Phthalates (PAEs) are considered endocrine-disrupting chemicals (EDCs), a series of compounds able to disrupt the normal regulation of the human endocrine-system. In the present study, we investigated the roles of four PAEs, butyl benzyl phthalate (BBP), dibutyl phthalate (DBP), dimethyl phthalate (DMP), and diethyl phthalate (DEP), in hepatocellular carcinoma (HCC) cells. We define novel roles for the PAEs on the migration of HCC cells via their enhancing of the interaction between the pregnane X receptor (PXR) and E26 transformation specific sequence 1 (ETS-1). Our results indicate that PAEs induced the transcriptional activation of ETS-1 and PXR. PXR activated by PAEs could bind to ETS-1 directly and enhanced the activity of ETS-1, which resulted in the induction of invasion-related ETS-1 target genes. The "LXXLL" motif in the ETS-1 C-terminal was essential for the interaction between PXR and ETS-1 induced by PAEs. Treatment of PAEs promoted the nuclear accumulation of ETS-1 or the recruitment of ETS-1, but not in cells expressing ETS-1 with a mutated LXXLL motif in its downstream gene promoter region, or following transfection of PXR siRNA. Treatment with the PXR antagonist ketoconazole almost completely inhibited the effects of PAEs. Moreover, PAEs enhanced the in vitro or in vivo invasion of HCC cells via PXR/ETS-1. Therefore, our results not only contribute to a better understanding of HCC, but also extended the roles of EDCs regulating human malignancies.
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http://dx.doi.org/10.1016/j.phrs.2021.105648DOI Listing
May 2021

Respiratory syncytial virus seasonality and prevention strategy planning for passive immunisation of infants in low-income and middle-income countries: a modelling study.

Lancet Infect Dis 2021 May 6. Epub 2021 May 6.

Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK; Respiratory Syncytial Virus Network (ReSViNET) Foundation, Zeist, Netherlands. Electronic address:

Background: Respiratory syncytial virus (RSV) represents a substantial burden of disease in young infants in low-income and middle-income countries (LMICs). Because RSV passive immunisations, including maternal vaccination and monoclonal antibodies, can only grant a temporary period of protection, their effectiveness and efficiency will be determined by the timing of the immunisation relative to the underlying RSV seasonality. We aimed to assess the potential effect of different approaches for passive RSV immunisation of infants in LMICs.

Methods: We included 52 LMICs in this study on the basis of the availability of RSV seasonality data and developed a mathematical model to compare the effect of different RSV passive immunisation approaches (seasonal approaches vs a year-round approach). For each candidate approach, we calculated the expected annual proportion of RSV incidence among infants younger than 6 months averted (effectiveness) and the ratio of per-dose cases averted between that approach and the year-round approach (relative efficiency).

Findings: 39 (75%) of 52 LMICs included in the study had clear RSV seasonality, defined as having more than 75% of annual RSV cases occurring in 5 or fewer months. In these countries with clear RSV seasonality, the seasonal approach in which monoclonal antibody administration began 3 months before RSV season onset was only a median of 16% (IQR 13-18) less effective in averting RSV-associated acute lower respiratory infection (ALRI) hospital admissions than a year-round approach, but was a median of 70% (50-97) more efficient in reducing RSV-associated hospital admissions per dose. The seasonal approach that delivered maternal vaccination 1 month before the season onset was a median of 27% (25-33) less effective in averting hospital admissions associated with RSV-ALRI than a year-round approach, but was a median of 126% (87-177) more efficient at averting these hospital admissions per dose.

Interpretation: In LMICs with clear RSV seasonality, seasonal approaches to monoclonal antibody and maternal vaccine administration might optimise disease prevention by dose given compared with year-round administration. More data are needed to clarify if seasonal administration of RSV monoclonal antibodies or maternal immunisation is programmatically suitable and cost effective in LMICs.

Funding: The Bill & Melinda Gates Foundation, World Health Organization.
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http://dx.doi.org/10.1016/S1473-3099(20)30703-9DOI Listing
May 2021

Development of a patient-reported outcome tool for assessing symptom burden during perioperative care in liver surgery: The MDASI-PeriOp-Hep.

Eur J Oncol Nurs 2021 Apr 28;52:101959. Epub 2021 Apr 28.

Institute for Cancer Care Innovation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Purpose: Based on the MD Anderson Symptom Inventory (MDASI), we developed a Patient-reported outcomes tool for hepatectomy perioperative care (MDASI-PeriOp-Hep).

Methods: To establish the content validity, we generated PeriOp-Hep-specific candidate items from qualitative interviews of patients (n = 30), and removed items that lacked clinical relevance on the basis of input from panels of patients, caregivers, and clinicians. The psychometric properties of the MDASI-PeriOp-Hep were validated (n = 150). The cognitive debriefing and clinical interpretability were assessed to confirm the ease of comprehension, relevance, and acceptability of the tool.

Results: Five symptoms specific to hepatectomy (abdominal bloating, tightness, or fullness; abdominal cramping; muscle weakness, instability, or vertigo; constipation; and incisional tightness) were identified as module items to form the MDASI-PeriOp-Hep. The Cronbach αs for symptoms and for interference were 0.898 and 0.861, respectively. The test-retest reliability was 0.887 for all 18 symptom severity items. Compared to other commonly used tools, correlation of MDASI-PeriOp-Hep scores to performance status (all, P < 0.001) and to the phase of perioperative care confirmed known-group validity. Convergent validity was excellent against other standard Patient-reported outcomes tools. Cognitive debriefing demonstrated that the MDASI-PeriOp-Hep was an easy to use and understandable tool.

Conclusions: For integrating patient-reported outcomes in perioperative patient care, a procedure-specific tool is desirable. The MDASI-PeriOp-Hep is a valid, reliable, concise tool for measuring symptom severity and functional interference in patients undergoing liver surgery.
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http://dx.doi.org/10.1016/j.ejon.2021.101959DOI Listing
April 2021

Prognostic value and characterization of NTRK1 variation by fluorescence in situ hybridization in esophageal squamous cell carcinoma.

J Cancer Res Clin Oncol 2021 May 8. Epub 2021 May 8.

Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.

Purpose: Rearrangement of the neurotrophic tyrosine kinase receptor (NTRK) 1 gene is a target of tropomyosin receptor kinase A (TRKA) inhibitors, and its targeted drug (larotrectinib) has been approved by the US Food and Drug Administration. We investigated the existence and prognostic importance of NTRK1 variation in esophageal squamous cell carcinoma (ESCC).

Methods: Fluorescence in situ hybridization of a NTRK1 rearrangement was conducted on 523 ESCC samples through tissue microarrays. Kaplan-Meier curves with log-rank tests were used to evaluate survival.

Results: We identified 8 (1.5%), 35(6.7%) and 109 (20.8%) cases with a NTRK1 rearrangement using 15%, 10% and 5% as cut-off values, respectively. We observed copy number (CN) variation of NTRK1 in some cases: 79 (15.1%) cases had a gain in NTRK1 CN ≥ 3, and 24 (4.6%) cases had NTRK1 CN ≥ 4. A NTRK1 rearrangement at the above-mentioned thresholds was not related to disease-free survival (DFS, P = 0.45, 0.47, 0.87) and overall survival (OS, P = 0.80, 0.74, 0.57), respectively. Gain in NTRK1 CN was associated with a poor prognosis irrespective of whether NTRK1 CN ≥ 4 (DFS, P = 0.015; OS, P = 0.035) or NTRK1 CN ≥ 3 (DFS, P = 0.039; OS, P = 0.025).

Conclusion: A NTRK1 rearrangement occurred rarely in ESCC. The increased CN of NTRK1 might be a prognostic indicator for DFS and OS in patients with ESCC.
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http://dx.doi.org/10.1007/s00432-021-03578-7DOI Listing
May 2021

3D Printing of Strontium Silicate Microcylinder-Containing Multicellular Biomaterial Inks for Vascularized Skin Regeneration.

Adv Healthc Mater 2021 May 8:e2100523. Epub 2021 May 8.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China.

The reconstruction of dermal blood vessels is essential for skin regeneration process. However, the lack of vascular structure, insufficient angiogenesis induction, and ineffective graft-host anastomosis of the existing skin substitutes are major bottle-necks for permanent skin replacement in tissue engineering. In this study, the uniform strontium silicate (SS) microcylinders are successfully synthesized and integrated into the biomaterial ink to serve as stable cell-induced factors for angiogenesis, and then a functional skin substitute based on a vascularization-induced biomimetic multicellular system is prepared via a "cell-writing" bioprinting technology. With an unprecedented combination of vascularized skin-mimicking structure and vascularization-induced function, the SS-containing multicellular system exhibits outstanding angiogenic activity both in vitro and in vivo. As a result, the bioprinted skin substitutes significantly accelerate the healing of both acute and chronic wounds by promoting the graft-host integration and vascularized skin regeneration in three animal models. Therefore, the study provides a referable strategy to fabricate biomimetic multicellular constructs with angiogenesis-induced function for regeneration of vascularized complex and hierarchical tissues.
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http://dx.doi.org/10.1002/adhm.202100523DOI Listing
May 2021

Physiological and transcriptional responses of Phalaris arundinacea under waterlogging conditions.

J Plant Physiol 2021 Apr 18;261:153428. Epub 2021 Apr 18.

Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, State Key Laboratory of Hydraulics and Mountain River Engineering Sichuan University, Chengdu, 610065, Sichuan, China. Electronic address:

As a high-yielding forage grass, Phalaris arundinacea widely distributed in the Qinghai-Tibet Plateau region of China. To explore physiological and molecular response mechanism of Phalaris arundinacea under waterlogging, we analyzed the biomass and physiological indexes of three locally grown strains under the submerged condition of 10 cm. The material Z0611 showed the strongest waterlogging resistance while the YS showed the weakest performance. Transcriptome sequencing analysis demonstrated that the YS and Z0611 had 17,010 and 7566 differently expression genes (DEGs), respectively, which were mainly concentrated in the metabolic process, cell, ribosome, phenylpropanoid biosynthesis pathway in GO and KEGG databases. We also identified a large number of genes involved in carbohydrate metabolism, hormone signaling regulation, transcription factors, antioxidant system, and ethylene signaling. Our research may provide a scientific basis for the restoration of wetland environment on the Qinghai-Tibet Plateau, and lay a foundation for further exploration of the waterlogging resistance genes of Phalaris arundinacea and breeding of new strains resistant with waterlogging stress.
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http://dx.doi.org/10.1016/j.jplph.2021.153428DOI Listing
April 2021

MiR-205-5p suppresses angiogenesis in gastric cancer by downregulating the expression of VEGFA and FGF1.

Exp Cell Res 2021 May 3:112579. Epub 2021 May 3.

Department of General Surgery, Peking University First Hospital, Beijing 100034, China. Electronic address:

Anti-angiogenic therapy represents one of the most promising treatment modalities for human cancers. However, the response to antiangiogenic therapy in gastric cancer (GC) remains dismal. To help identify new strategies for antiangiogenic therapy in GC, we evaluated miR-205-5p expression in GC tissues from TCGA database and our hospital, and its functions in angiogenesis were explored in vitro and in vivo. We investigated miR-205-5p expression and microvessel densities (MVDs) in GC tissues and liver metastases from patients. The function and mechanisms of miR-205-5p were examined in human cell lines and in xenograft mouse models. Associations between miR-205-5p expression and clinical characteristics were analyzed using either Pearson's χ test or Fisher's exact test. Differences in overall survival (OS) distributions were evaluated using the log-rank test. Differences in measurement data were compared using Student's t-test and one-way ANOVA. We found that miR-205-5p expression was downregulated in GC tissues and was negatively correlated with CD31 expression in both TCGA and our clinical samples. GC cell lines expressed low levels of miR-205-5p, and miR-205-5p upregulation significantly impaired the proliferation and angiogenesis of GC cells. Moreover, vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 1 (FGF1) expression and activation of extracellular-related kinase (ERK) signaling were suppressed by miR-205-5p. MiR-205-5p inhibition promoted malignant phenotypes by enhancing VEGFA and FGF1 expression, as well as the activation of ERK signaling. Angiogenesis and ERK signaling were decreased in response to VEGFA and FGF1 downregulation induced by miR-205-5p overexpression. The dual-luciferase reporter assay showed that VEGFA and FGF1 were direct targets of miR-205-5p. Xenograft mouse models revealed that miR-205-5p suppressed tumor growth by inhibiting neovascularization. Altogether, these results demonstrate that miR-205-5p suppresses angiogenesis in GC by attenuating the expression of VEGFA and FGF1, indicating that upregulation of miR-205-5p may represent as an antiangiogenic therapy for GC.
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http://dx.doi.org/10.1016/j.yexcr.2021.112579DOI Listing
May 2021

Clinical Efficacy of the Preservation of the Hepatic Branch of the Vagus Nerve on Delayed Gastric Emptying After Laparoscopic Pancreaticoduodenectomy.

J Gastrointest Surg 2021 May 5. Epub 2021 May 5.

Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave., Wuhan, 430030, Hubei, China.

Background: Delayed gastric emptying (DGE) is a common complication following laparoscopic pancreaticoduodenectomy (LPD), although it remains incompletely understood, and only few studies have investigated the clinical benefits of hepatic branch of the vagus nerve (HBVN) preservation on DGE after LPD until now. We intended to evaluate the effect of preservation of the HBVN during LPD on the incidence of DGE.

Methods: A total of 274 consecutive LPDs performed at a single center between July 2014 and December 2019 with available videos were retrospectively reviewed. DGE was defined according to the International Study Group of Pancreatic Surgery (ISGPS) criteria, and HBVN condition during the LPD procedure was evaluated through a video review. Risk factors associated with DGE were assessed by performing univariate and multivariate logistic regression analyses. Postoperative outcomes between the HBVN-preserved and HBVN-injury groups were compared before and after propensity score matching (PSM).

Results: One hundred fifty-six (56.93%) patients underwent LPD with HBVN-preserved and 118 (43.07%) with HBVN injury. DGE occurred in 33.2% of patients (n = 91) with grades B and C occurring at 13.9% (n = 38) and 7.7% (n = 21), respectively. Longer operative time, more EIBL, HBVN injury, POPF (grades B and C), postoperative hemorrhage, intra-abdominal infection, and Clavien-Dindo ≥III were identified as risk factors for DGE in the univariate analysis. Then, in the multivariate analysis, HBVN injury and intra-abdominal infection were found to be independent risk factors affecting the incidence of DGE (any grade) or clinically relevant DGE (grades B and C). Furthermore, the prevalence of DGE was significantly higher in the HBVN-injury group than in the HBVN-preserved group before and after PSM analysis (46.61% vs. 23.08%, P<0.001; 42.59% vs. 23.15%, P=0.013).

Conclusions: HBVN preservation during LPD might be associated with a reduced incidence of DGE as a framework for prospective quality improvement.
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http://dx.doi.org/10.1007/s11605-021-05024-yDOI Listing
May 2021

Genome sequencing sheds light on the contribution of structural variants to Brassica oleracea diversification.

BMC Biol 2021 May 5;19(1):93. Epub 2021 May 5.

National Engineering Research Center for Vegetables, Beijing Academy of Agriculture and Forestry Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops (North China), Beijing Key Laboratory of Vegetable Germplasm Improvement, Beijing, 100097, China.

Background: Brassica oleracea includes several morphologically diverse, economically important vegetable crops, such as the cauliflower and cabbage. However, genetic variants, especially large structural variants (SVs), that underlie the extreme morphological diversity of B. oleracea remain largely unexplored.

Results: Here we present high-quality chromosome-scale genome assemblies for two B. oleracea morphotypes, cauliflower and cabbage. Direct comparison of these two assemblies identifies ~ 120 K high-confidence SVs. Population analysis of 271 B. oleracea accessions using these SVs clearly separates different morphotypes, suggesting the association of SVs with B. oleracea intraspecific divergence. Genes affected by SVs selected between cauliflower and cabbage are enriched with functions related to response to stress and stimulus and meristem and flower development. Furthermore, genes affected by selected SVs and involved in the switch from vegetative to generative growth that defines curd initiation, inflorescence meristem proliferation for curd formation, maintenance and enlargement, are identified, providing insights into the regulatory network of curd development.

Conclusions: This study reveals the important roles of SVs in diversification of different morphotypes of B. oleracea, and the newly assembled genomes and the SVs provide rich resources for future research and breeding.
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http://dx.doi.org/10.1186/s12915-021-01031-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097969PMC
May 2021

Concurrent chemoradiotherapy versus radiotherapy alone for patients with locally advanced esophageal squamous cell carcinoma in the era of intensity modulated radiotherapy: a propensity score-matched analysis.

Thorac Cancer 2021 May 5. Epub 2021 May 5.

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: To investigate the survival benefit of concurrent chemoradiotherapy (CCRT) for patients with locally advanced esophageal squamous cell carcinoma (ESCC) during the years of intensity-modulated radiotherapy (IMRT).

Methods: Medical records of 1089 patients with ESCC who received IMRT from January 2005 to December 2017 were retrospectively reviewed. A total of 617 patients received CCRT, 472 patients received radiotherapy (RT) alone. Propensity score matching (PSM) method was used to eliminate baseline differences between the two groups. Survival and toxicity profile were evaluated afterward.

Results: After a median follow-up time of 47.9 months (3.2-149.8 months), both overall survival (OS) and progression-free survival (PFS) of the CCRT group were better than those of the RT alone group, either before or after PSM. After PSM, the 1-, 3-, and 5-year OS of RT alone and CCRT groups were 59.0% versus 70.2%, 27.7% versus 40.5% and 20.3% versus 33.1%, respectively (p < 0.001). The 1-, 3-, and 5-year PFS were 39.4% versus 49.0%, 18.3% versus 30.4% and 10.5% versus 25.0%, respectively (p < 0.001). The rates of ≥ grade 3 leukopenia and radiation esophagitis in the CCRT group were higher than that of RT alone group (p < 0.05). There was no significant difference in the probability of radiation pneumonitis between the two groups (p = 0.167). Multivariate Cox analysis indicated that female, EQD2 ≥60 Gy and concurrent chemotherapy were favorable prognostic factors for both OS and PFS.

Conclusions: Concurrent chemotherapy can bring survival benefits to patients with locally advanced ESCC receiving IMRT. For patients who cannot tolerate concurrent chemotherapy, RT alone is an effective alternative with promising results.
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http://dx.doi.org/10.1111/1759-7714.13971DOI Listing
May 2021

Bmcas-1 plays an important role in response against BmNPV infection in vitro.

Arch Insect Biochem Physiol 2021 May 5:e21793. Epub 2021 May 5.

Jiangsu Key Laboratory of Sericultural Biology and Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu, China.

Apoptosis, as one kind of innate immune system, is involved in host response against pathogens innovation. Caspases play a vital role in the execution stage of host cell apoptosis. It has been reported that Bmcaspase-1 (Bmcas-1) has a close relationship with Bombyx mori nucleopolyhedrovirus (BmNPV) infection for its differentially expressed patterns after viral infection. However, its underlying response mechanism is still unclear. The significant differential expression of Bmcas-1 in different tissues of differentially resistant strains revealed its vital role in BmNPV infection. To further validate its role in BmNPV infection, budded virus (BV)-eGFP was analyzed after knockdown and overexpression of Bmcas-1 by small interfering RNA and the pIZT-mCherry vector, respectively. The reproduction of BV-eGFP obviously increased at 72 h after knockdown of Bmcas-1, and decreased after overexpression in BmN cells. Moreover, the conserved functional domain of Cas-1 among different species and the closed evolutionary relationship of Cas-1 in Lepidoptera hinted that Bmcas-1 might be associated with apoptosis, and this was also validated by the apoptosis inducer, Silvestrol, and the inhibitor, Z-DEVD-FMK. Therefore, Bmcas-1 plays an essential antiviral role by activating apoptosis, and this result lays a fundament for clarifying the molecular mechanism of silkworm in response against BmNPV infection and breeding of resistant strains.
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http://dx.doi.org/10.1002/arch.21793DOI Listing
May 2021

MIR205 host gene (MIR205HG) drives osteosarcoma metastasis via regulating the microRNA 2114-3p (miR-2114-3p)/twist family bHLH transcription factor 2 (TWIST2) axis.

Bioengineered 2021 Dec;12(1):1576-1586

Department of Clinical Laboratory, Hunan Cancer Hospital & the Affiliated Cancer Hospital of Xiangya School of Medicine Central South University, Changsha, PR, China.

Osteosarcoma (OS) is an aggressive malignant tumor with a high rate of lung metastasis and a lack of therapeutic targets. Although the anomalous expression of long non-coding RNA (lncRNA) has been extensively documented in human cancer, its contribution to OS metastasis remains poorly understood. In this study, we found that MIR205 host gene (MIR205HG) was significantly elevated in human OS tissues, especially in metastatic OS tissues. Stable knockdown of MIR205HG inhibited OS cell invasion and lung metastatic foci formation, but did not affect cell viability. The vast majority of MIR205HG was situated in the cytosol, and served as a competing endogenous RNA (ceRNA) that directly bound to microRNA 2114-3p (miR-2114-3p), resulting in increased twist family bHLH transcription factor 2 (TWIST2) level. Pre-clinically, high MIR205HG was linked with dismal overall and relapse-free survival. Functionally, the attenuated cell invasion caused by MIR205HG knockdown was effectively rescued by miR-2114-3p silencing or TWIST2 overexpression. Overall, our findings suggest that the previously uncharacterized regulatory axis of MIR205HG/miR-2114-3p/TWIST2 plays a critical role in promoting OS metastasis, which implies a potential therapeutic target in OS patients with metastasis.
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http://dx.doi.org/10.1080/21655979.2021.1920326DOI Listing
December 2021

Prognostic value of CCR2 as an immune indicator in lung adenocarcinoma: A study based on tumor-infiltrating immune cell analysis.

Cancer Med 2021 May 4. Epub 2021 May 4.

Department of Immunology, School of Basic Medicine, Qingdao University, Qingdao, Shandong Province, China.

Background: Prognostic indicators in lung adenocarcinoma (LUAD) have been seeking under database analysis, and remarkable advance is on the way.

Methods: This study calculated the scores of stromal and immune components of the tumor microenvironment (TME) in 551 LUAD samples using the ESTIMATE algorithm on The Cancer Genome Atlas (TCGA) database. R package ''limma'' was used to selected differentially expressed genes (DEG). We have analyzed the DEGs by means of Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichments. The protein-protein network, univariate Cox analysis, and Lasso regression analysis were performed to selected survival-related genes. Gene Set Enrichment Analysis (GSEA) represented the enriched pathway of CC chemokine receptor 2 (CCR2). The ratios of immune cells in the TME of each LUAD sample were obtained using the R package "limma" and CIBERSORT algorithm in R 4.0.2.

Results: The ImmuneScore was positively correlated with prognosis regarding survival rate, T classification of TNM stages, and clinicopathological staging characteristics. GO and KEGG enrichments showed DEGs were associated with immune-related activities. Three genes of LUAD were selected from the PPI network and Cox proportional hazards regression analysis. CCR2 was the most survival correlated gene by Lasso regression analysis. GSEA results showed that C2 kegg gene sets in the CCR2 high-expression group were mainly enriched in the B cell or T cell receptor signaling pathway and natural killer cell-mediated cytotoxicity. Correlation of CCR2 expression with prognosis was conducted, implicating a positive correlation with the prognosis of survival rate and M classification, negative correlation with the prognosis of T and N classifications. The correlation between CCR2 and tumor-infiltrating immune cells (TICs) was analyzed, and 14 kinds of TICs were found closely correlated with CCR2 expression through difference analysis.

Conclusion: Therefore, CCR2 has prognostic value as an immune indicator in LUAD.
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http://dx.doi.org/10.1002/cam4.3931DOI Listing
May 2021

N6-methyladenosine demethylase FTO impairs hepatic ischemia-reperfusion injury via inhibiting Drp1-mediated mitochondrial fragmentation.

Cell Death Dis 2021 May 4;12(5):442. Epub 2021 May 4.

Department of Hepatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Despite N6-methyladenosine (m6A) is functionally important in various biological processes, its role and the underlying regulatory mechanism in the liver remain largely unexplored. In the present study, we showed that fat mass and obesity-associated protein (FTO, an m6A demethylase) was involved in mitochondrial function during hepatic ischemia-reperfusion injury (HIRI). We found that the expression of m6A demethylase FTO was decreased during HIRI. In contrast, the level of m6A methylated RNA was enhanced. Adeno-associated virus-mediated liver-specific overexpression of FTO (AAV8-TBG-FTO) ameliorated the HIRI, repressed the elevated level of m6A methylated RNA, and alleviated liver oxidative stress and mitochondrial fragmentation in vivo and in vitro. Moreover, dynamin-related protein 1 (Drp1) was a downstream target of FTO in the progression of HIRI. FTO contributed to the hepatic protective effect via demethylating the mRNA of Drp1 and impairing the Drp1-mediated mitochondrial fragmentation. Collectively, our findings demonstrated the functional importance of FTO-dependent hepatic m6A methylation during HIRI and provided valuable insights into the therapeutic mechanisms of FTO.
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http://dx.doi.org/10.1038/s41419-021-03622-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096847PMC
May 2021