Publications by authors named "Fei Xiong"

340 Publications

Realization of Super-Large-Diameter Slurry Shield Passing through Settlement-Sensitive Area Based on Unreinforced Disturbance Control Technology.

Comput Intell Neurosci 2022 13;2022:6299645. Epub 2022 Jan 13.

School of Civil Engineering, Chongqing University, Chongqing 400045, China.

Due to the complex construction conditions of shield tunnels, ground disturbance is inevitable during the construction process, which leads to surface settlement and, in serious cases, damage to surrounding buildings (structures). Therefore, it is especially important to effectively control the constructive settlement of subway tunnels when crossing settlement-sensitive areas such as high-density shantytowns. Based on the project of Wuhan Metro Line 8 Phase I, the shield of Huangpu Road Station-Xujiapang Road Station interval crossing high-density shantytowns, we study the disturbance control technology of oversized diameter mud and water shield crossing unreinforced settlement-sensitive areas during the construction process. By optimizing the excavation parameters and evaluating the ground buildings, the excavation process can be monitored at the same time, and the water pressure, speed, and tool torque required during the excavation during the construction process can be finely adjusted; the control of tunneling process parameters can provide reference and basis for analyzing the construction control of large-diameter shield through old shantytowns.
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http://dx.doi.org/10.1155/2022/6299645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776489PMC
January 2022

Prognostic and Clinicopathologic Significance of Neutrophil-to-Lymphocyte Ratio in Esophageal Cancer: An Update Meta-Analysis.

Technol Cancer Res Treat 2022 Jan-Dec;21:15330338211070140

117922Hubei Cancer Hospital, Wuhan, China.

Esophageal cancer is one of the most common cancers with significant morbidity and mortality. It is important to predict the prognosis of patients. The purpose of this study was to comprehensively assess the prognostic and clinicopathologic significance of NLR in patients with esophageal cancer. A systematic literature search was performed using PubMed, Cochrane Library, Embase, Web of Science, MEDLINE, and CNKI. This meta-analysis was conducted in accordance with PRISMA guidelines. Hazard ratio (HR) with 95% confidence interval (CI) was used as the effect estimation to evaluate the prognostic role of NLR. Odds ratio (OR) was used to evaluate the relation between NLR and clinicopathologic characteristics. A total of 8431 patients from 32 studies were included in this meta-analysis. The pooled results showed that elevated NLR might predict poor prognosis: The factors considered included overall survival (OS) (HR, 1.57; 95% CI, 1.40-1.75;  < .001), cancer-specific survival (CSS) (HR, 1.28; 95% CI, 1.09-1.49;  < .001), progression-free survival (PFS) (HR, 1.45; 95% CI, 1.29-1.72;  < .001), and disease-free survival (DFS) (HR,1.58; 95% CI, 1.27-1.97;  < .001). High NLR was also associated with tumor differentiation, tumor length, tumor invasion depth, lymph node metastasis, and clinical stage. No significant association was observed between NLR and metastasis stage (OR, 1.69; 95% CI, 0.98-2.98;  = .058). The results of this meta-analysis suggest that elevated NLR value might predict poor prognosis (OS, CSS, PFS, and DFS), according to abnormal clinicopathologic parameters.
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http://dx.doi.org/10.1177/15330338211070140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785352PMC
January 2022

Proanthocyanidin A1 promotes the production of platelets to ameliorate chemotherapy-induced thrombocytopenia through activating JAK2/STAT3 pathway.

Phytomedicine 2022 Jan 5;95:153880. Epub 2021 Dec 5.

State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China. Electronic address:

Background: Chemotherapy-induced thrombocytopenia (CIT) is a severe adverse drug reaction, and the main reason for CIT is the destruction of megakaryocytes (MKs, precursor cells of platelet) in bone marrow by chemotherapy. Peanut skin, the seed coat of Arachis hypogaea L., is a traditional Chinese medicine commonly used to treat thrombocytopenia. However, its active compounds and the mechanisms remain unclear.

Purpose: This study aims to clarify the active compounds of peanut skin to exhibit thrombogenic effects against CIT and their underlying mechanisms in vitro and in vivo.

Study Design: The bioassay-guided isolation based on the proliferation of MKs was used to explore the possible platelet-enhancing ingredients in peanut skin. HSCCC technique coupled with preparative HPLC was used to separate the active compounds. Dami cells and carboplatin-treated mice model were used to evaluate the thrombogenic effects of PS-1. Network pharmacology, molecular docking, dynamics simulation studies, kinase activity, surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), isothermal dose-response fingerprint (ITDRF) and western blot analysis were performed to investigate the mechanisms of PS-1.

Results: Proanthocyanidin A1 (PS-1) and its stereoisomers (PS-2-4) were demonstrated to promote the proliferation of MKs (Dami cells), especially PS-1 (EC = 8.58 μM). Further studies demonstrated that PS-1 could induce the differentiation of Dami cells in dose/time-dependent manner. Biological target analysis showed that PS-1 directly bound to JAK2 (KD = 2.06 μM) to exert potent activating effect (EC = 0.66 μM). Oral administration of PS-1 (25 or 50 mg/kg) significantly improved CIT, but this effect was confirmed to be inhibited by JAK2 inhibitor AG490, indicating that PS-1 exerted its efficacy through JAK2 in vivo.

Conclusion: Proanthocyanins (PS-1-4) derived from peanut skin were first clarified as platelet-enhancing ingredients to improve CIT. The underlying mechanism of PS-1 was proved to promote the proliferation and differentiation of MKs via JAK2/STAT3 pathway both in vitro and in vivo.
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http://dx.doi.org/10.1016/j.phymed.2021.153880DOI Listing
January 2022

High-performance SOD mimetic enzyme [email protected] for arresting cell cycle and proliferation of acute myeloid leukemia.

Bioact Mater 2022 Apr 18;10:117-130. Epub 2021 Aug 18.

State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano-Science and Technology, Southeast University, Nanjing, 210096, PR China.

SOD-like activity of CeO nanoparticles (Ce NPs) is driven by Ce/Ce, high oxidative stress can oxidize Ce to reduce the ratio of Ce/Ce, inactivating the SOD activity of Ce NPs. Herein, we found [email protected] NPs, assembled by Au NPs and Ce NPs, exhibited high-performance of SOD mimetic enzyme activity even upon the oxidation of HO. Ce NPs supported by nano-Au can acquire the electrons from Au NPs through the enhanced localized surface plasmon resonance (LSPR), maintaining the stability of Ce/Ce and SOD-like activity. Meanwhile, [email protected] NPs retained the peroxidase function and catalase function. As a result, [email protected] NPs effectively scavenged O•- and the derived ROS in AML cells, which are the important signaling source that drives AML cell proliferation and accelerates cell cycle progression. When HL-60 cells were treated by [email protected] NPs, the removal of endogenous ROS signal significantly arrested cell cycle at G1 phase and suppressed the cell proliferation by blocking the mitogen-activated protein kinases (MAPKs) signaling and the Akt/Cyclin D1 cell cycle signaling. Importantly, this treatment strategy showed therapeutic effect for subcutaneous transplantation of AML model as well as a satisfactory result in diminishing the leukocyte infiltration of liver and spleen particularly. Thus, assembled [email protected] NPs show the high-performance SOD-like activity, promising the potential in treating AML and regulating abnormal ROS in other diseases safely and efficiently.
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http://dx.doi.org/10.1016/j.bioactmat.2021.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637344PMC
April 2022

MiR-155-5p suppresses SOX1 to promote proliferation of cholangiocarcinoma via RAF/MEK/ERK pathway.

Cancer Cell Int 2021 Dec 7;21(1):656. Epub 2021 Dec 7.

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

Background: Accumulating evidence has demonstrated the close relation of SOX1 with tumorigenesis and tumor progression. Upregulation of SOX1 was recently shown to suppress growth of human cancers. However, the expression and role of SOX1 in cholangiocarcinoma (CCA) is not well characterized.

Methods: Expression levels of SOX1 in CCA tissues and normal bile duct tissues were examined using public GEO database. Western blot and immunohistochemistry were used to confirm the expression levels. Cell proliferation assay (CCK-8) and colony formation assay were performed to assess proliferation of CCA cells. A mouse model of subcutaneous transplantable tumors was used to evaluated proliferation of CCA in vivo. The putative regulating factor of SOX1 were determined using Targetscan and dual-luciferase reporter assay.

Results: SOX1 was downregulated in CCA tissues. Overexpression of SOX1 significantly inhibited cell proliferation in vitro and suppressed tumor growth in vivo. miR-155-5p directly targeted the 3'-untranslated region (3'UTR) of SOX1 and inhibited expression of SOX1, resulting in the activation of RAF, MEK and ERK phosphorylation, and thus CCA proliferation. However, restoration of SOX1 expression in miR-155-5p overexpressing cell lines decreased the phosphorylation level of RAF, MEK and ERK, as well as the proliferation of CCA cells.

Conclusion: MiR-155-5p decreased the expression of SOX1 by binding to its 3'UTR, which activated the RAF/MEK/ERK signaling pathway and promoted CCA progression.
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http://dx.doi.org/10.1186/s12935-021-02374-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650398PMC
December 2021

Accumulation and physicochemical properties of starch in relation to eating quality in different parts of taro (Colocasia esculenta) corm.

Int J Biol Macromol 2022 Jan 28;194:924-932. Epub 2021 Nov 28.

Jiangsu Key Laboratory of Crop Genetics and Physiology/Co-Innovation Center for Modern Production Technology of Grain Crops/Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University, Yangzhou 225009, China; Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding/Jiangsu Co-Innovation Center for Modern Production Technology of Grain Crops, Yangzhou University, Yangzhou 225009, China. Electronic address:

The accumulation and physicochemical properties of starch affect the eating quality of taro corm. This study aims to investigate the accumulation, morphology, and physicochemical properties of starch from inner and outer tissues in the top, middle, and basal parts of taro corm. Structural and morphological observations showed that the inner tissues of the taro corm accumulated more starch, and the middle tissue had moderate amylose content and the largest granule diameter. Starch from different tissues exhibited A-type orthorhombic structure and similar nuclear magnetic resonance spectrum. The relative crystallinity of starch in the middle tissue was higher than that in the top and basal tissues. Compared with middle and basal tissues, starch from top tissue showed higher peak viscosity, pasting time, swelling power and solubility. Compared with the top and basal tissues, the middle tissue of taro corm exhibited higher index of eating quality including smell, texture, and total evaluation score. The results indicated that starches in various spatial parts of taro corm exhibit differences in accumulation, morphology, structure and physicochemical properties that lead to diverse eating qualities.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.11.147DOI Listing
January 2022

Discovery of Eucalyptin C, derived from the fruits of Eucalyptus globulus Labill., as a novel selective PI3Kγ inhibitor for immunosuppressive treatment.

Chin J Nat Med 2021 Nov;19(11):844-855

State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

The fruits of Eucalyptus globulus Labill. are known to have a plenty of medicinal properties, such as anti-tumor, anti-inflammatory, and immunosuppressive activity. Our previous study found that the phloroglucinol-sesquiterpene adducts in the fruits of E. globulus were immunosuppressive active constituents, especially Eucalyptin C (EuC). Phosphoinositide 3-kinases-γ (PI3Kγ) plays a pivotal role in T cell mediated excessive immune responses. In this study, EuC was first discovered to be a novel selective PI3Kγ inhibitor with an IC value of 0.9 μmol·L and selectivity over 40-fold towards the other PI3K isoforms. Molecular docking, molecular dynamics simulation, and cellular thermal shift assay showed that EuC bound to PI3Kγ. Furthermore, EuC suppressed the downstream of PI3Kγ to induce the apoptosis and inhibit the activation of primary spleen cells derived from allergic contact dermatitis mice. This work highlights the role of the fruits of E. globulus as a source of bioactive plant with immunosuppressive activity.
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http://dx.doi.org/10.1016/S1875-5364(21)60111-5DOI Listing
November 2021

A case report of precocious puberty related to Rett syndrome and a literature review.

Pharmazie 2021 Nov;76(11):559-561

Department of Paediatrics, West China Second University Hospital; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China;, Email:

Rett syndrome is an X-linked dominant disorder, and the typical phenotype includes intractable epileptic seizures and severe mental retardation, in particular, a rapid regression in language and limited progress in psychomotor development. Premature breast and pubic hair development and advanced bone age are signs of precocious puberty (PP), defined as puberty occurring before 8 years of age in girls. There are rare reports about precious puberty associated with Rett syndrome. Herein, we report the case of a patient with Rett syndrome with precocious puberty. Her first signs of PP occurred 6 months prior to presentation (at 7.5 years old), and the laboratory measurements, including tests of bone age and gonadotropin-releasing hormone stimulation, were positive for PP. PP was controlled after treatment with leuprorelin 3.75 mg for one year. In addition, the genetic and phenotypic spectrum of previously reported cases of Rett syndrome with precocious puberty are reviewed and summarized.
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http://dx.doi.org/10.1691/ph.2021.1747DOI Listing
November 2021

The Fractured Wire After Femoral Vein Catheterisation.

Authors:
Yang Liu Fei Xiong

Eur J Vasc Endovasc Surg 2021 Nov 22;62(5):766. Epub 2021 Oct 22.

Department of Vascular Surgery, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

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http://dx.doi.org/10.1016/j.ejvs.2021.09.024DOI Listing
November 2021

Comparison of PET/CT and MRI in the Diagnosis of Bone Metastasis in Prostate Cancer Patients: A Network Analysis of Diagnostic Studies.

Front Oncol 2021 4;11:736654. Epub 2021 Oct 4.

Department of Sports Medicine, Wuxi 9th People's Hospital Affiliated to Soochow University, Wuxi, China.

Background: Accurate diagnosis of bone metastasis status of prostate cancer (PCa) is becoming increasingly more important in guiding local and systemic treatment. Positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) have increasingly been utilized globally to assess the bone metastases in PCa. Our meta-analysis was a high-volume series in which the utility of PET/CT with different radioligands was compared to MRI with different parameters in this setting.

Materials And Methods: Three databases, including Medline, Embase, and Cochrane Library, were searched to retrieve original trials from their inception to August 31, 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The methodological quality of the included studies was assessed by two independent investigators utilizing Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). A Bayesian network meta-analysis was performed using an arm-based model. Absolute sensitivity and specificity, relative sensitivity and specificity, diagnostic odds ratio (DOR), and superiority index, and their associated 95% confidence intervals (CI) were used to assess the diagnostic value.

Results: Forty-five studies with 2,843 patients and 4,263 lesions were identified. Network meta-analysis reveals that 68Ga-labeled prostate membrane antigen (68Ga-PSMA) PET/CT has the highest superiority index (7.30) with the sensitivity of 0.91 and specificity of 0.99, followed by 18F-NaF, 11C-choline, 18F-choline, 18F-fludeoxyglucose (FDG), and 18F-fluciclovine PET/CT. The use of high magnetic field strength, multisequence, diffusion-weighted imaging (DWI), and more imaging planes will increase the diagnostic value of MRI for the detection of bone metastasis in prostate cancer patients. Where available, 3.0-T high-quality MRI approaches 68Ga-PSMA PET/CT was performed in the detection of bone metastasis on patient-based level (sensitivity, 0.94 0.91; specificity, 0.94 0.96; superiority index, 4.43 4.56).

Conclusions: 68Ga-PSMA PET/CT is recommended for the diagnosis of bone metastasis in prostate cancer patients. Where available, 3.0-T high-quality MRI approaches 68Ga-PSMA PET/CT should be performed in the detection of bone metastasis.
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http://dx.doi.org/10.3389/fonc.2021.736654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522477PMC
October 2021

Advances in the DNA methylation hydroxylase TET1.

Biomark Res 2021 Oct 16;9(1):76. Epub 2021 Oct 16.

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

Background: The ten-eleven translocation 1 (TET1) protein is a 5-methylcytosine hydroxylase that belongs to the TET protein family of human α-ketoglutarate oxygenases. TET1 recognizes and binds to regions of high genomic 5'-CpG-3' dinucleotide density, such as CpG islands, initiates the DNA demethylation program, and maintains DNA methylation and demethylation balance to maintain genomic methylation homeostasis and achieve epigenetic regulation. This article reviews the recent research progress of TET1 in the mechanism of demethylation, stem cells and immunity, various malignant tumours and other clinical diseases.

Conclusion: TET1 acts as a key factor mediating demethylation, the mechanism of which still remains to be investigated in detail. TET1 is also critical in maintaining the differentiation pluripotency of embryonic stem cells and plays anti- or oncogenic roles in combination with different signalling pathways in different tumours. In certain tumours, its role is still controversial. In addition, the noncatalytic activity of TET1 has gradually attracted attention and has become a new direction of research in recent years.
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http://dx.doi.org/10.1186/s40364-021-00331-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520278PMC
October 2021

Interleukin-6 receptor alpha and CD27 discriminate intratumoral T helper 17 subpopulations with distinct functional properties in a mouse lung cancer model.

Immun Inflamm Dis 2021 12 27;9(4):1749-1758. Epub 2021 Sep 27.

The Department of Thoracic Surgery, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei Province, China.

Background: T helper 17 (Th17) cells actively participate in the tumor immune response in lung cancer. However, the heterogeneity and plasticity of intratumoral Th17 cells in lung cancer remain elusive. In this study, Th17 subpopulations were characterized in a mouse lung cancer model.

Methods: Urethane was administered to induce lung cancer in interleukin (IL)-17-EGFP transgenic mice. Flow cytometry was used to analyze the phenotypes, signaling status, and functions of Th17 subpopulations either in vivo or in vitro. The adoptive transfer assay and real-time polymerase chain reaction were applied to analyze the plasticity of Th17 subpopulations.

Results: IL-6Rα CD27 Th17 and IL-6Rα CD27 Th17 were identified in intratumoral Th17 cells. The two subpopulations expressed equivalent RORγt. However, the former expressed higher T-bet but lower Foxp3, more IL-17A and IFN-γ but less IL-10 than the latter. Furthermore, IL-6Rα CD27 Th17 moderately inhibited the proliferation of lung cancer cells while IL-6Rα CD27 Th17 could not. IL-6Rα CD27 Th17 exhibited weaker Jun N-terminal kinases (JNK) signaling but stronger signal transducer and activator of transcription 3 (Stat3) signaling than IL-6Rα CD27 Th17. The adoptive transfer assay indicated that both subpopulations downregulated RORγt in recipients' spleens but maintained RORγt in recipients' lungs. Meanwhile, IL-6Rα CD27 Th17 expressed higher T-bet and IFN-γ than IL-6Rα CD27 Th17 in the recipients. IL-6Rα CD27 Th17 expressed Foxp3 and IL-10 in recipients' spleens but not lungs.

Conclusions: This study reveals intratumoral Th17 subpopulations with distinct functional properties and signaling patterns, thus offering valuable insight into Th17 heterogeneity and plasticity in lung cancer.
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http://dx.doi.org/10.1002/iid3.533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589402PMC
December 2021

Affects Nitrogen Metabolism by Sucrose Transport Signaling in Rice ( L.).

Front Plant Sci 2021 10;12:703034. Epub 2021 Sep 10.

Jiangsu Key Laboratory of Crop Genetics and Physiology/Co-Innovation Center for Modern Production Technology of Grain Crops/Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University, Yangzhou, China.

Carbon and nitrogen antagonistically regulate multiple developmental processes. However, the molecular mechanism affecting nitrogen metabolism by sucrose transport remains poorly defined. Previously, we noted that () mediated sucrose transport by binding to the promoter regions of (), , and . Here, we note that promotes nitrogen uptake and then maintains the ratio of fresh weight to dry weight in seedling plants and the effective leaf blade at flowering stages. Mutants of the sucrose transporter gene displayed a phenotype similar to that of . By microarray analysis and qRT-PCR in mutant plants, affected the transcription level of amino acid metabolism-related genes. We further found that mainly amino acid contents were reduced in flag leaves but increased in seeds. Both sugar and organic nitrogen changes caused the ratio of fresh weight to dry weight to decrease in mutant seedling plants and mature leaves, which might result in vigorous reduced metabolic activity and become less susceptible to stress. These results demonstrated that affected nitrogen metabolism by sugar distribution in rice, which provided new insight that coordinated with C and N balance to maintain plant growth activity.
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http://dx.doi.org/10.3389/fpls.2021.703034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461328PMC
September 2021

The relationship between characteristics of root morphology and grain filling in wheat under drought stress.

PeerJ 2021 19;9:e12015. Epub 2021 Aug 19.

Jiangsu Key Laboratory of Crop Genetics and Physiology/Co-Innovation Center for Modern Production Technology of Grain Crops/Joint International Research Laboratory of Agriculture & Agri-Product Safety of the Ministry of Education, Yangzhou University, Yangzhou, Jiangsu, China.

Drought is a common yield limiting factor in wheat production and has become a significant threat to global food security. Root system is the organ responsible for water uptake from soil and root growth is closely associated with yield and quality of wheat. However, the relationship between morphological and structural characteristics of root growth and caryopsis enrichment in wheat under drought stress is unclear. In this study, two wheat cultivars (YM13 and YN19) were treated with drought from flowering to caryopsis maturity stage. The changes in morphological structure of roots and characteristics of endosperm enrichment were investigated. Drought stress significantly reduced the root length, plant height, root dry weight and aboveground parts dry weight, whereas the root-shoot ratio of YM13 and YN19 increased by 17.65% and 8.33% under drought stress, respectively. The spike length, spike weight, grains number per spike and 1,000-grains weight of mature wheat also significantly declined under drought stress. Meanwhile, the cross section structure of roots was changed with the enlargement of vascular cylinder and dense distribution of xylem vessels under drought stress. Additionally, drought stress affected the substance enrichment in wheat caryopses, decreasing starch accumulation and increasing protein accumulation of endosperm. Correlation analysis suggested that the root length was closely correlated with the relative areas of amyloplast (0.51) and protein body (0.70), and drought stress increased the correlation coefficient (0.79 and 0.78, respectively). While the root dry weight had a significantly positive correlation with the plant height and aboveground parts dry weight. The results can provide theoretical basis for root architecture optimization, water-saving and high-yield cultivation and quality improvement in wheat.
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http://dx.doi.org/10.7717/peerj.12015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380422PMC
August 2021

Menkes disease diagnosed by a frameshift mutation in a patient with infantile spasms-a case report.

Transl Pediatr 2021 Jul;10(7):1965-1971

Department of Pediatrics, West China Second University Hospital of Sichuan University.

Menkes disease (MD) is a rare congenital copper deficiency disease caused by an adenosine triphosphatase copper transporting alpha () gene mutation. It is a progressive and systemic disease that primarily involves the central nervous system and connective tissues. The clinical manifestation of these patients with MD is curly hair, progressive muscle tone reduction, and convulsions, and often leads to death in early infancy. Herein, we present a case of a 9-month-old Chinese male who displayed developmental regression, followed by convulsions, which were characterized by infantile spasms (ISs). The proband also had curly hair, hypopigmented skin, cutis laxa, decreased muscle tone, and micrognathia. The patient's ceruloplasmin levels were below the reference values. Brain magnetic resonance imaging (MRI) showed abnormal signals bilaterally that were symmetrically distributed in the caudate nucleus, globus pallidus, and subcortical white matter of the temporal parietal cortex, white matter in the anterior and posterior corners of the ventricles and the anterior limb of the internal capsule. The electroencephalograph (EEG) showed hypsarrhythmia. Genetic testing revealed a novel frameshift mutation in the gene exon 13 and premature termination codon. Copper replacement therapy was initiated after the delayed diagnosis was established. However, the patient still died several months later due to disease progression. Our case reveals a novel frameshift mutation of the gene, which expands the gene spectrum of MD. The infants with uncontrollable convulsions, regressive development, curly hair, MD should be considered at early stage and also need the further genetic analysis to confirm MD finally. The correct and timely diagnosis and initiating copper replacement therapy may improve the prognosis.
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http://dx.doi.org/10.21037/tp-21-275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349949PMC
July 2021

MBD2 acts as a repressor to maintain the homeostasis of the Th1 program in type 1 diabetes by regulating the STAT1-IFN-γ axis.

Cell Death Differ 2022 01 21;29(1):218-229. Epub 2021 Aug 21.

The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China.

The methyl-CpG-binding domain 2 (MBD2) interprets DNA methylome-encoded information through binding to the methylated CpG DNA, by which it regulates target gene expression at the transcriptional level. Although derailed DNA methylation has long been recognized to trigger or promote autoimmune responses in type 1 diabetes (T1D), the exact role of MBD2 in T1D pathogenesis, however, remains poorly defined. Herein, we generated an Mbd2 knockout model in the NOD background and found that Mbd2 deficiency exacerbated the development of spontaneous T1D in NOD mice. Adoptive transfer of Mbd2 CD4 T cells into NOD.scid mice further confirmed the observation. Mechanistically, Th1 stimulation rendered the Stat1 promoter to undergo a DNA methylation turnover featured by the changes of DNA methylation levels or patterns along with the induction of MBD2 expression, which then bound to the methylated CpG DNA within the Stat1 promoter, by which MBD2 maintains the homeostasis of Th1 program to prevent autoimmunity. As a result, ectopic MBD2 expression alleviated CD4 T cell diabetogenicity following their adoptive transfer into NOD.scid mice. Collectively, our data suggest that MBD2 could be a viable target to develop epigenetic-based therapeutics against T1D in clinical settings.
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http://dx.doi.org/10.1038/s41418-021-00852-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8738722PMC
January 2022

Discovery of Novel Apigenin-Piperazine Hybrids as Potent and Selective Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors for the Treatment of Cancer.

J Med Chem 2021 08 18;64(16):12089-12108. Epub 2021 Aug 18.

State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China.

Poly (ADP-ribose) polymerase-1 (PARP-1) is a potential target for the discovery of chemosensitizers and anticancer drugs. Amentoflavone () is reported to be a selective PARP-1 inhibitor. Here, structural modifications and trimming of have led to a series of derivatives () and apigenin-piperazine/piperidine hybrids (, , , and ), respectively. Among these compounds, exhibited a potent PARP-1 inhibitory effect (IC = 14.7 nM) and possessed high selectivity to PARP-1 over PARP-2 (61.2-fold). Molecular dynamics simulation and the cellular thermal shift assay revealed that directly bound to the PARP-1 structure. In and studies, showed a potent chemotherapy sensitizing effect against A549 cells and a selective cytotoxic effect toward SK-OV-3 cells through PARP-1 inhibition. also displayed good ADME characteristics, pharmacokinetic parameters, and a desirable safety margin. These findings demonstrated that may serve as a lead compound for chemosensitizers and the (BRCA-1)-deficient cancer therapy.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00735DOI Listing
August 2021

Changes of dendritic cell and natural killer cell on the cord blood with idiopathic fetal growth restriction.

J Matern Fetal Neonatal Med 2021 Aug 11:1-6. Epub 2021 Aug 11.

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, PR China.

Objective: To investigate the characteristics of dendritic cells (DC) and natural killer cells (NK) in umbilical cord blood of pregnant patients diagnosed with idiopathic fetal growth restriction (IFGR).

Methods: A prospective study cohort of IFGR patients was established who were in the third trimester (28-36 weeks), with a healthy, pregnant woman cohort selected as controls. Umbilical cord blood was collected.

Results: The study included 50 pregnant women in the IFGR group and 50 pregnant women in the healthy, control group. The incidence of SGA in the IFGR group was 52.0%, and the incidence of preterm birth was 18.0%. The incidence of neonatal complications in neonates with live birth in the IFGR group was 12.0%. The birth weight, body length and placental weight of the newborns in the IFGR group were significantly lower than those in the control group ( < .05). Flow cytometry revealed no significant difference in the proportion or maturity of DC in umbilical cord blood between IFGR group and control group ( > .05). The proportion of NK cells in umbilical cord blood of IFGR group was significantly higher than that of normal control group. The proportion of CD56dimCD16+ NK cells was also significantly higher than that of the normal control group ( < .05), but the expression of NK cell surface killing activator receptor NKG2D and inhibitory receptor NKG2A was not statistically significant ( > .05).

Conclusion: The number and proportion of DC cells in cord blood may not be the key factors affecting the outcomes observed during FGR pregnancies. However, we found the proportion of NK cells in cord blood to be significantly increased, as well as the ratio of CD56dimCD16 + NK to CD56highCD16-NK to be imbalanced, which may be one of the pathogenesis of the pathological pregnancy leading to IFGR.
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http://dx.doi.org/10.1080/14767058.2021.1951214DOI Listing
August 2021

Activated invariant natural killer T cells infiltrate aortic tissue as key participants in abdominal aortic aneurysm pathology.

Immunology 2021 12 19;164(4):792-802. Epub 2021 Aug 19.

Vascular Surgery of West China Hospital, Sichuan University, Chengdu, China.

Adaptive immunity and innate immunity have been implicated in the pathogenesis of abdominal aortic aneurysm (AAA), and damage and remodelling in the tunica media are a focus of the aneurysm development. Thus, identification of key immune cells or molecules that might be targets for the treatment of AAA is critical. We characterized the innate immune cells in human AAA tissue specimens by flow cytometry and found that apart from other lymphocytes, many invariant natural killer T (iNKT) cells marked as CD3 and Va24Ja18 had invaded the aortic tissues and were numerous, especially in the tunica media. These infiltrating iNKT cells have a high expression of CD69, indicating a highly active function. We were interested in whether iNKT cells could be the drivers of media damage in AAA. To answer this question, we used an AAA mouse model induced by angiotensin II (Ang II) infusion, which can reproduce the inflammatory response of AAA in mouse, which was confirmed by RNAseq. The results showed that the incidence of AAA was significantly higher after administration of α-galactosylceramide (α-GalCer), a synthetic glycolipid that activates iNKT cells via CD1d, compared with the Ang II-induced AAA alone (61·54% vs 31·82%) in mice. Histopathological and immunofluorescent staining results showed significantly more severe inflammatory infiltration and pathological lesions in the Ang II+α-GalCer treatment group. These results are highly suggestive that activated iNKT cells greatly contribute to AAA development and that the control of the activation state in iNKT cells may represent an important therapeutic strategy for AAA.
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http://dx.doi.org/10.1111/imm.13401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561115PMC
December 2021

Immediate vs delayed cord clamping in preterm infants: A systematic review and meta-analysis.

Int J Clin Pract 2021 Nov 1;75(11):e14709. Epub 2021 Sep 1.

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.

To compare and evaluate the efficacy and safety of immediate cord clamping (ICC) and delayed cord clamping (DCC) in preterm infants. We performed a comprehensive and systematic meta-analysis of randomised controlled trials (RCTs) assessing ICC and DCC in preterm infants by searching PUBMED, EMBASE, Science Direct, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang Database (from inception to 30 September 2020). Summary odds ratios or mean differences with 95% confidence intervals were calculated using a fixed- or random-effect model. A total of 20 RCTs with 1807 preterm infants were included in the study. DCC provided more benefits in increasing the haematocrit and haemoglobin levels at 24 hours of life (%), thus reducing the incidence of anaemia, necrotising enterocolitis, length of hospital stay and mortality than when ICC was performed. No significant differences were found between ICC and DCC in terms of peak bilirubin level; need for blood transfusion, mechanical ventilation (MV) and phototherapy; duration of MV and phototherapy; and incidences of intraventricular haemorrhage, retinopathy of prematurity, patent ductus arteriosus, respiratory distress syndrome, sepsis, jaundice, polycythaemia, periventricular leukomalacia and bronchopulmonary dysplasia. DCC is a safe, beneficial and feasible intervention for preterm infants. However, rigorously designed and large-scale RCTs are necessary to identify the role and ideal timing of DCC.
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http://dx.doi.org/10.1111/ijcp.14709DOI Listing
November 2021

Plastin-3 is a diagnostic and prognostic marker for pancreatic adenocarcinoma and distinguishes from diffuse large B-cell lymphoma.

Cancer Cell Int 2021 Aug 4;21(1):411. Epub 2021 Aug 4.

Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China.

Background: Altered Plastin-3 (PLS3; an actin-binding protein) expression was associated with human carcinogenesis, including pancreatic ductal adenocarcinoma (PDA). This study first assessed differentially expressed genes (DEGs) and then bioinformatically and experimentally confirmed PLS3 to be able to predict PDA prognosis and distinguish PDA from diffuse large B-cell lymphoma.

Methods: This study screened multiple online databases and revealed DEGs among PDA, normal pancreas, diffuse large B-cell lymphoma (DLBCL), and normal lymph node tissues and then focused on PLS3. These DEGs were analyzed for Gene Ontology (GO) terms, Kaplan-Meier curves, and the log-rank test to characterize their association with PDA prognosis. The receiver operating characteristic curve (ROC) was plotted, and Spearman's tests were performed. Differential PLS3 expression in different tissue specimens (n = 30) was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR).

Results: There were a great number of DEGs between PDA and lymph node, between PDA and DLBCL, and between PDA and normal pancreatic tissues. Five DEGs (NET1, KCNK1, MAL2, PLS1, and PLS3) were associated with poor overall survival of PDA patients, but only PLS3 was further verified by the R2 and ICGC datasets. The ROC analysis showed a high PLS3 AUC (area under the curve) value for PDA diagnosis, while PLS3 was able to distinguish PDA from DLBCL. The results of Spearman's analysis showed that PLS3 expression was associated with levels of KRT7, SPP1, and SPARC. Differential PLS3 expression in different tissue specimens was further validated by RT-qPCR.

Conclusions: Altered PLS3 expression was useful in diagnosis and prognosis of PDA as well as to distinguish PDA from DLBCL.
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http://dx.doi.org/10.1186/s12935-021-02117-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336331PMC
August 2021

Revisiting the Antigen-Presenting Function of β Cells in T1D Pathogenesis.

Front Immunol 2021 14;12:690783. Epub 2021 Jul 14.

The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Type 1 diabetes (T1D) is characterized by the unresolved autoimmune inflammation and islet β cell destruction. The islet resident antigen-presenting cells (APCs) including dendritic cells and macrophages uptake and process the β cell-derived antigens to prime the autoreactive diabetogenic T cells. Upon activation, those autoreactive T cells produce copious amount of IFN-γ, TNF-α and IL-1β to induce β cell stress and death. Autoimmune attack and β cell damage intertwine together to push forward this self-destructive program, leading to T1D onset. However, β cells are far beyond a passive participant during the course of T1D development. Herein in this review, we summarized how β cells are actively involved in the initiation of autoimmune responses in T1D setting. Specifically, β cells produce modified neoantigens under stressed condition, which is coupled with upregulated expression of MHC I/II and co-stimulatory molecules as well as other immune modules, that are essential properties normally exhibited by the professional APCs. At the cellular level, this subset of APC-like β cells dynamically interacts with plasmacytoid dendritic cells (pDCs) and manifests potency to activate autoreactive CD4 and CD8 T cells, by which β cells initiate early autoimmune responses predisposing to T1D development. Overall, the antigen-presenting function of β cells helps to explain the tissue specificity of T1D and highlights the active roles of structural cells played in the pathogenesis of various immune related disorders.
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http://dx.doi.org/10.3389/fimmu.2021.690783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318689PMC
November 2021

Quiescent-Interval Slice-Selective MRA Accurately Estimates Intravascular Stent Dimensions Prior to Intervention in Patients With Peripheral Artery Disease.

J Magn Reson Imaging 2022 01 29;55(1):246-254. Epub 2021 Jul 29.

Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, South Carolina, USA.

Background: Quiescent-interval slice-selective (QISS) magnetic resonance angiography (MRA) is a non-contrast alternative for the pre-procedural assessment of patients with peripheral artery disease (PAD). However, the feasibility of pre-procedural stent size estimation using QISS MRA would merit investigation.

Purpose: To evaluate the feasibility of QISS MRA for pre-procedural stent size estimation in PAD patients compared to computed tomography angiography (CTA).

Study Type: Retrospective.

Subjects: Thirty-three PAD patients (68 ± 9 years, 18 men, 15 women).

Field Strength/sequence: Two-dimensional balanced steady-state free precession QISS MRA at 1.5 T and 3 T.

Assessment: All patients received QISS MRA and CTA of the lower extremity run-off followed by interventional digital subtraction angiography (DSA). Stenotic lesion length and diameter were quantified (AMF and AVS with 3 and 13 years of experience in cardiovascular imaging, respectively) to estimate the dimensions of the stent necessary to restore blood flow in the treated arteries. Measured dimensions were adjusted to the closest stent size available.

Statistical Tests: The Friedman test with subsequent pairwise Wilcoxon signed-rank test was used to compare the estimated stent dimensions between QISS MRA, CTA, and the physical stent size used for intervention. Intra-class correlation (ICC) analysis was performed to assess inter-reader agreement. Significant differences were considered at P < 0.05.

Results: No significant difference was observed between estimated stent diameter by QISS MRA or CTA compared to physical stent diameter (8.9 ± 2.9 mm, 8.8 ± 3.0 mm, and 8.8 ± 3.8 mm, respectively; χ  = 1.45, P = 0.483). There was a significant underestimation of stent length for both QISS MRA and CTA, compared to physical stent length (45.8 ± 27.8 mm, 46.4 ± 29.3 mm, and 50.4 ± 34.0 mm, respectively; χ  = 11.96) which could be corrected when measurements were adjusted to the next available stent length (χ  = 2.38, P = 0.303). Inter-reader assessment showed good to excellent agreement between the readers (all ICC ≥0.81).

Data Conclusion: QISS MRA represents a reliable method for pre-procedural lesion assessment and stent diameter and length estimation in PAD patients.

Level Of Evidence: 3 TECHNICAL EFFICACY: Stage 2.
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http://dx.doi.org/10.1002/jmri.27864DOI Listing
January 2022

Platinum-based chemotherapy nanocarriers and co-delivery of multiple drugs.

Biomater Sci 2021 Sep 14;9(18):6023-6036. Epub 2021 Sep 14.

School of Biomedical Engineering, Sun Yat-sen University, Shenzhen 518057, China.

Platinum-based anticancer drugs can inhibit the growth of cancer cells by disrupting DNA replication, which makes them widely applicable in clinics for treating tumors and cancers. However, owing to the intrinsic or acquired drug resistance and severe side effects caused in the treatment, their successful clinical applications have been limited. Various strategies have been used to address these challenges. Nanocarriers have been used for platinum drug delivery because they can be effectively deposited in tumor tissues to reduce the damage to normal organs for an enhanced permeability and retention (EPR) effect. Furthermore, for synergizing the function of platinum-based drugs with different mechanisms to decrease the toxicities, multicomponent chemotherapy has become an imperative strategy in clinical cancer treatments. This review aims to introduce the mechanisms of action and limitations of platinum-based drugs in clinics, followed by providing the current advancement of nanocarriers including lipids, polymers, dendrimers, micelles and albumin for platinum drug delivery in cancer treatments. In addition, multicomponent chemotherapy based on platinum drugs is introduced in detail. Finally, the prospects of multicomponent chemotherapy for cancer treatment are discussed as well.
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http://dx.doi.org/10.1039/d1bm00879jDOI Listing
September 2021

A heterozygous variant in is associated with a newly named neurodevelopmental disorder Arboleda-Tham syndrome-a case report.

Transl Pediatr 2021 Jun;10(6):1748-1754

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.

Arboleda-Tham syndrome (OMIM#616268) is a newly named neurodevelopmental disorder, which is an autosomal dominant hereditary disease characterized by genetic variants. The clinical manifestations include global developmental delay, primary microcephaly, and craniofacial dysmorphism, as well as more varied features such as feeding difficulties, cardiac defects, and ocular anomalies. Currently, due to restricted knowledge of Arboleda-Tham syndrome and less specific pathological manifestations, it is difficult to diagnose at the early stages of the disease. Here, we present a case with obvious growth retardation and intellectual disability, accompanied by other manifestations including dysmorphic features of the ears, facial dysmorphism, right cryptorchidism, and inguinal hernia. Routine laboratory tests including blood-urine tandem mass spectrometry, urine gas chromatographic mass spectrometry, karyotype, echocardiography, automatic auditory brainstem responses, serum levels of calcium, phosphorus, vitamin D, creatine kinase (CK), and CK isoenzyme (CK-MB), and brain magnetic resonance imaging showed negative results. A heterozygous variant in , c.57delA (p.Val20*), was detected by trio-based whole exome sequencing and subsequent validation by Sanger sequencing in the patient, which was absent in both the parents. The patient received rehabilitation and nutritional intervention. The testis reduction and orchiopexy was scheduled when he was 1 year old. Our report extends the phenotype-genotype map of Arboleda-Tham syndrome, and also expands the mutant spectrum of the gene. Moreover, this case emphasizes the timely conduction of whole exome sequencing for the early diagnosis of Arboleda-Tham syndrome, and spares patients from meaningless examinations and ineffective treatments.
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http://dx.doi.org/10.21037/tp-21-206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261581PMC
June 2021

Sucrose transporter in rice.

Plant Signal Behav 2021 11 16;16(11):1952373. Epub 2021 Jul 16.

Jiangsu Key Laboratory of Crop Genetics and Physiology/Co-Innovation Center for Modern Production Technology of Grain Crops/Joint International Research Laboratory of Agriculture &agri-product Safety, Yangzhou University, Yangzhou, China.

Plant photosynthesis processes play vital roles in crop plant development. Understanding carbohydrate partitioning via sugar transport is one of the potential ways to modify crop biomass, which is tightly linked to plant architecture, such as plant height and panicle size. Based on the literature, we highlight recent findings to summarize phloem loading by sucrose transport in rice. In rice, sucrose transporters, (sucrose transporters) and (sugars are eventually exported transporters) import sucrose and export cells between phloem parenchyma cells and companion cells. Before sucrose transporters perform their functions, several transcription factors can induce sucrose transporter gene transcription levels, such as DNA binding with one finger 11 () and Nuclear Factor Y B1 (). In addition to native regulator genes, environmental factors, such as CO concentration, drought stress and increased temperature, also affect sucrose transporter gene transcription levels. However, more research work is needed on formation regulation webs. Elucidation of the phloem loading mechanism could improve our understanding of rice development under multiple conditions and facilitate its manipulation to increase crop productivity.
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http://dx.doi.org/10.1080/15592324.2021.1952373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525984PMC
November 2021

Myhre Syndrome Misdiagnosed as Marfan Syndrome: an Educational Presentation.

Braz J Cardiovasc Surg 2021 10 17;36(5):700-702. Epub 2021 Oct 17.

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China.

A 32-month-old girl with patent ductus arteriosus, false tendon of left ventricle, mild pulmonary hypertension, and chronic cardiac insufficiency (cardiac function level I-II) was misdiagnosed with Marfan Syndrome and there was no improvement in her physical growth after operation for this disease. The preterm baby was finally diagnosed with Myhre Syndrome by clinical phenotypes and mutation of SMAD4 gene.
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http://dx.doi.org/10.21470/1678-9741-2020-0592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597609PMC
October 2021

Corrigendum to: Autophagy in regulatory T cells: A double-edged sword in disease settings [Mol. Immunol. 109 (2019) 43-50].

Mol Immunol 2021 Sep 29;137:41. Epub 2021 Jun 29.

The Center for Biomedical Research, Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Huazhong University of Science and Technology, 1095 Jiefang Ave., Wuhan, 430030, China. Electronic address:

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http://dx.doi.org/10.1016/j.molimm.2021.03.013DOI Listing
September 2021

The MAPK dual specific phosphatase (DUSP) proteins: A versatile wrestler in T cell functionality.

Int Immunopharmacol 2021 Sep 28;98:107906. Epub 2021 Jun 28.

The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China. Electronic address:

The functional state of T cells is diverse and under dynamic control for adapting to the changes of microenvironment. Reversible protein phosphorylation represents an important post-translational modification that not only involves in the immediate early response of T cells, but also affects their functionality in the long run. Perturbation of global phosphorylation profile and/or phosphorylation of specific signaling nodes result in aberrant T cell activity. Dual specific phosphatases (DUSPs), which target MAPKs and beyond, have increasingly been emerged as a versatile regulator in T cell biology. Herein in this mini review, we sought to summarize and discuss the impact of DUSP proteins on the regulation of effector T cell activity, T cell polarization, regulatory T cell development and T cell senescence/exhaustion. Given the distinctive engagement of each DUSP member under various disease settings such as chronic infection, autoimmune disorders, cancer and age-related diseases, DUSP proteins likely hold the promise to become a druggable target other than the existing therapeutics that are predominantly by manipulating protein kinase activity.
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http://dx.doi.org/10.1016/j.intimp.2021.107906DOI Listing
September 2021
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