Publications by authors named "He Wang"

1,441 Publications

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Widespread aberrant functional connectivity throughout the whole brain in obstructive sleep apnea.

Front Neurosci 2022 1;16:920765. Epub 2022 Aug 1.

College of Precision Instrument and Optoelectronics Engineering, Tianjin University, Tianjin, China.

Objective: Obstructive sleep apnea (OSA) is a sleep-related breathing disorder with high prevalence and is associated with cognitive impairment. Previous neuroimaging studies have reported abnormal brain functional connectivity (FC) in patients with OSA that might contribute to their neurocognitive impairments. However, it is unclear whether patients with OSA have a characteristic pattern of FC changes that can serve as a neuroimaging biomarker for identifying OSA.

Methods: A total of 21 patients with OSA and 21 healthy controls (HCs) were included in this study and scanned using resting-state functional magnetic resonance imaging (fMRI). The automated anatomical labeling (AAL) atlas was used to divide the cerebrum into 90 regions, and FC between each pair of regions was calculated. Univariate analyses were then performed to detect abnormal FCs in patients with OSA compared with controls, and multivariate pattern analyses (MVPAs) were applied to classify between patients with OSA and controls.

Results: The univariate comparisons did not detect any significantly altered FC. However, the MVPA showed a successful classification between patients with OSA and controls with an accuracy of 83.33% ( = 0.0001). Furthermore, the selected FCs were associated with nearly all brain regions and widely distributed in the whole brain, both within and between, many resting-state functional networks. Among these selected FCs, 3 were significantly correlated with the apnea-hypopnea index (AHI) and 2 were significantly correlated with the percentage of time with the saturation of oxygen (SaO) below 90% of the total sleep time (%TST < 90%).

Conclusion: There existed widespread abnormal FCs in the whole brain in patients with OSA. This aberrant FC pattern has the potential to serve as a neurological biomarker of OSA, highlighting its importance for understanding the complex neural mechanism underlying OSA and its cognitive impairment.
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http://dx.doi.org/10.3389/fnins.2022.920765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377518PMC
August 2022

Predict the Progression of Cervical Intraepithelial Neoplasia by a Novel Marker Folate Combine with FRα, p16 and Ki-67.

Int J Gen Med 2022 9;15:6529-6538. Epub 2022 Aug 9.

Department of Gynecology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People's Republic of China.

Purpose: To study the expression of serum folate and red blood cell (RBC) folate, folate receptor α (FRα), p (p16), and Ki-67 at different levels of cervical intraepithelial neoplasia (CIN) and then analyze their role in the progression of CIN and their value as an early warning indicator of CIN progression.

Patients And Methods: We randomly collected the data of patients at the Department of Gynecology in Guangxi Medical University Affiliated Cancer Hospital from January 2016 to December 2018: Normal controls (149 cases), CIN1 (150 cases), CIN2 (100 cases), and CIN3 (101 cases). [Ethical approval by Ethics Committee of the Second Hospital of Shanxi Medical University. (2013) No. (001-1)]. The expression of serum folate and RBC folate was detected by the chemiluminescence method, while the expression of FRα, p16, and Ki-67 was detected by Streptavidin-Perosidase (SP) immunohistochemistry.

Results: There was no statistically significant difference in serum folate levels between different grades of CIN (P=0.784), but the RBC folate levels were statistically significant (P=0.015), and there was a negative correlation between RBC folate levels and CIN lesion grades (P<0.05). The FRα, p16, and Ki-67 levels in the CIN group were significantly different from those in the normal control group (P <0.01), and a positive correlation was found (P <0.01); FRα positivity (P=0.000), Ki-67 positivity (P=0.000), and low-level RBC folate (P=0.000) were independent risk factors for the progression of CIN; these indicators were combined to establish a random forest (RF) model in which the Ki-67+FRα model was used as the early warning model of CIN progression.

Conclusion: RBC folate, FRα, p16, and Ki-67 can be used as valuable clinical test indicators for predicting the progression of CIN; the combined detection model of Ki-67+FRα can be used as an early warning model for predicting the progression of CIN.
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http://dx.doi.org/10.2147/IJGM.S362685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375578PMC
August 2022

Potentials and challenges of chromosomal microarray analysis in prenatal diagnosis.

Front Genet 2022 26;13:938183. Epub 2022 Jul 26.

Department of Medical Genetics, West China Second University Hospital, Sichuan University, Chengdu, China.

For decades, conventional karyotyping analysis has been the gold standard for detecting chromosomal abnormalities during prenatal diagnosis. With the development of molecular cytogenetic methods, this situation has dramatically changed. Chromosomal microarray analysis (CMA), a method of genome-wide detection with high resolution, has been recommended as a first-tier test for prenatal diagnosis, especially for fetuses with structural abnormalities. Based on the primary literature, this review provides an updated summary of the application of CMA for prenatal diagnosis. In addition, this review addresses the challenges that CMA faces with the emergence of genome sequencing techniques, such as copy number variation sequencing, genome-wide cell-free DNA testing, and whole exome sequencing. The CMA platform is still suggested as priority testing methodology in the prenatal setting currently. However, pregnant women may benefit from genome sequencing, which enables the simultaneous detection of copy number variations, regions of homozygosity and single-nucleotide variations, in near future.
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http://dx.doi.org/10.3389/fgene.2022.938183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360565PMC
July 2022

Interfacial Modulation on CoFeO Epitaxial Thin Films for Anomalous Hall Sensor Applications.

ACS Appl Mater Interfaces 2022 Aug 11. Epub 2022 Aug 11.

School of Microelectronics, Xi'an Jiaotong University, Xi'an 710049, China.

Magnetic oxide films with a strong anomalous Hall effect (AHE) have attracted much attention due to their strong sensitivity and high polarization for magnetic sensor applications. However, the linearity of the anomalous Hall sensors still needs improving. In this work, we propose to use the interface regulation to improve the linearity of the AHE. We grow spinel ferrite CoFeO (CoFeO) thin films on MgAlO (MAO) substrates and alter their interfacial properties by inserting a graphene layer between the MAO substrate and the CoFeO film. Through a detailed structure and performance analysis, it reveals that the insertion of graphene has not broken the epitaxial nature of the films but endows the film with a nanopillar-like structure. A series of electrical tests show that the Hall resistance signal of our thin film system has high sensitivity and high linearity to the magnetic field. Reduced hysteresis and better linearity of the anomalous Hall resistance were found in the graphene-inserted heterostructure due to differences in the nanostructure and possibly interfacial coupling. These results suggest that interfacial engineering offers a pathway to tune the performance of ferrite thin film systems for sensor applications.
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http://dx.doi.org/10.1021/acsami.2c07575DOI Listing
August 2022

[Lysosomal enzyme analysis of mucolipidosis type II α/β and type III α/β in two Chinese pedigrees].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 Aug;39(8):829-835

Department of Medical Genetics and Prenatal Diagnosis Center, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

Objective: To analyze the characteristics of lysosomal enzymes in mucolipidosis (ML) type II α/β and type III α/β for the choice of enzyme evaluating indicators.

Methods: Multiple lysosomal enzymes including α-iduronidase (IDUA), α -N-acetylglucosaminidase (NAGLU), β-galactosidase-1 (GLB1), β-glucuronidase (GUSB), α-galactosidase A (GLA), glucocerebrosidase (GBA) and arylsulphatase A (ASA) in plasma and leukocyte of two Chinese pedigrees with ML type II α/β and type III α/β and healthy controls were determined. Previous publications on ML type II α/β and type III α/β during the last five years were retrieved from PubMed, CNKI and WanFang databases by using "mucolipidosis" as key word.

Results: The activities of several lysosomal enzymes were increased in the plasma of both patients: ASA, IDUA (20-fold) > GUSB (10-fold) > GLB1, GLA (5-fold) > NAGLU (2-fold), whilst there was no significant change in GBA. The activities of several lysosomal enzymes in the leukocyte of the two patients were normal. 15 lysosomal enzymes have been used in 22 previous studies, the most frequently used were hexosaminidase A and B (Hex A+B) (12 papers), α-mannosidase (α-man) (11 papers) and GUSB (10 papers). The degree of Hex A+B and α-man elevation was most obvious (24.4-fold and 24.7-fold on average respectively), followed by ASA (22.4-fold on average), GUSB is 18.8-fold on average.

Conclusion: Based on the lysosomal enzyme analysis of the two cases and literature review, ASA, GUSB, Hex A+B and α-man are recommended as the evaluating indicators for lysosomal enzyme analysis of ML type II α/β and type III α/β.
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http://dx.doi.org/10.3760/cma.j.cn511374-20210830-00706DOI Listing
August 2022

Widespread protein N-phosphorylation in organism revealed by [email protected] beads based mild-acidic enrichment method.

Talanta 2022 Jul 16;251:123740. Epub 2022 Jul 16.

CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R & A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.

Protein phosphorylation is one of the most commonly studied and ubiquitous post-translational modifications (PTMs), and defining site-specific phosphorylation is essential to understand basic and disease biology. However, the chemical properties and biological activities hamper the detection of non-canonical N-phosphorylation from biological samples, and the study of N-phosphorylation over the last half century has lagged behind canonical O-phosphorylation. Here, a mild-acidic method based-on [email protected] beads was developed for protein N-phosphorylation sites identification. The method was verified as an effective complement for neutral enrichment science the stability of N-phosphorylation varied with the protein context. We firstly verified the feasibility of the mild-acidic enrichment strategy by standard peptides. Totally, 301 and 1476 N-phosphorylation sites were identified from E. coli and HeLa, respectively, verifying the robust of the method. The results greatly enriched N-phosphorylation site database. Furthermore, the method provided the peptide sequence motif of the N-phosphorylation sites and the biological functions of the identified proteins. The work represented an important step forward in studying the role of N-phosphorylation and other labile phosphorylation.
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http://dx.doi.org/10.1016/j.talanta.2022.123740DOI Listing
July 2022

Coherent vibrational dynamics of Au(SR) nanoclusters.

Chem Sci 2022 Jul 17;13(27):8124-8130. Epub 2022 Jun 17.

Hefei National Research Center for Physical Sciences at the Microscale, Department of Chemical Physics, University of Science and Technology of China Hefei Anhui 230026 China

The coherent vibrational dynamics of gold nanoclusters (NCs) provides important information on the coupling between vibrations and electrons as well as their mechanical properties, which is critical for understanding the evolution from a metallic state to a molecular state with diminishing size. Coherent vibrations have been widely explored in small-sized atomically precise gold NCs, while it remains a challenge to observe them in large-sized gold NCs. In this work, we report the coherent vibrational dynamics of atomically precise Au(SR) NCs temperature-dependent femtosecond transient absorption (TA) spectroscopy. The population dynamics of Au(SR) consists of three relaxation processes: internal conversion, core-shell charge transfer and relaxation to the ground state. After removing the population dynamics from the TA kinetics, fast Fourier transform analysis on the residual oscillation reveals distinct vibrational modes at 1.5 THz (50 cm) and 2 THz (67 cm), which arise from the wavepacket motions along the ground-state and excited-state potential energy surfaces (PES), respectively. These results are helpful for understanding the physical properties of gold nanostructures with a threshold size that lies in between those of molecular-like NCs and metallic-state nanoparticles.
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http://dx.doi.org/10.1039/d2sc02246jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278113PMC
July 2022

Individualized and clinically friendly helmet-type coil positioning method (I-Helmet) for transcranial magnetic stimulation.

Brain Stimul 2022 Jul 31;15(5):1023-1025. Epub 2022 Jul 31.

Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China; Neuroscience Center, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, China. Electronic address:

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http://dx.doi.org/10.1016/j.brs.2022.07.045DOI Listing
July 2022

A novel CLCNKB variant in a Chinese family with classic Bartter syndrome and prenatal genetic diagnosis.

Mol Genet Genomic Med 2022 Aug 1:e2027. Epub 2022 Aug 1.

Department of Obstetrics & Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.

Background: Type III Bartter syndrome (BS), often known as classic Bartter syndrome is caused by variants in CLCNKB gene, which encoding the basolateral chloride channel protein ClC-Kb, and is characterized by renal salt wasting, hypokalemia, metabolic alkalosis, increased renin, and aldosterone levels.

Methods: A 2-year-old boy presented severe malnutrition, severe metabolic alkalosis and severe hypokalemia and was clinically diagnosed with BS. The trio exome sequencing (ES) was performed to discover the genetic cause of this patient, followed by validation using Sanger sequencing and quantitative polymerase chain reaction subsequently.

Results: The genetic analysis indicated that this patient with a compound heterozygous variants of CLCNKB gene including a novel nonsense variant c.876 T > A and a whole-gene deletion. The two variants were inherited from his parents, respectively. Subsequently, target sequencing of CLCNKB gene was performed for next pregnancy, and prenatal genetic diagnosis was provided for the family.

Conclusions: The results of current study identified the compound heterozygous variants in a patient with classic BS. The novel variant expands the spectrum of CLCNKB variants in BS. Our study also indicates that ES is an alternative tool to simultaneously detect single-nucleotide variants and copy-number variants.
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http://dx.doi.org/10.1002/mgg3.2027DOI Listing
August 2022

Recognition between CD147 and cyclophilin A deciphered by accelerated molecular dynamics simulations.

Phys Chem Chem Phys 2022 Aug 10;24(31):18905-18914. Epub 2022 Aug 10.

MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, School of Physics, Xi'an Jiaotong University, Xi'an 710049, China.

CD147 functions as the receptor of extracellular cyclophilin A (CypA) in various diseases, and CD147-CypA binding ulteriorly underlies the pathological process of various viral infections including HIV-1, SARS, and SARS-CoV-2. Although CyPA has been identified as a key intermediate pro-inflammatory factor, the mechanism by which CD147 cooperates with CypA in the development of the cytokine storm remains largely unknown, and the binding profile of CD147 with CypA remains to be elucidated as well. Here, we prepared three binding models of the CD147-CypA complex, including the active site of CypA severally binding to the groove bound by the Ig1 and Ig2 domains (model-0), P180-G181 (model-1), and P211 (model-2) of CD147, as well as introducing mutations P180A-G181A and P211A individually in each model. All systems were studied using accelerated molecular dynamics simulations and the molecular mechanics generalized Born surface area (MM/GBSA) method. For model-0, CypA bound to the ectodomain of CD147 with the highest binding affinity. Moreover, mutations P180A-G181A of CD147 in model-0 decreased the binding affinity and weakened the dynamic correlation between CD147 and CypA, which resulted in CypA shifting from the initial binding location. Other residue mutations of CD147 did not significantly affect the CD147-CypA binding, as reflected by the energy and structural analyses. Compared with surface plasmon resonance results and nuclear magnetic resonance shift signals, CypA should tend to reciprocally bind to the groove of CD147, and the binding process might be modulated by P180-G181 rather than P211. Besides, residue R201 of CD147 is critical for CD147-CypA binding and needs further experimental verification. These findings further our understanding of the recruitment between CD147 and CypA and its potential role in the development of inflammation and viral infection.
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http://dx.doi.org/10.1039/d2cp01975bDOI Listing
August 2022

Imaging Mass Cytometry Analysis of immune Checkpoint Inhibitor-Related Pneumonitis: A Case Report.

Front Immunol 2022 15;13:899971. Epub 2022 Jul 15.

Department of Pathology, Peking University First Hospital, Beijing, China.

Immune checkpoint inhibitor-related pneumonitis (CIP) is a rare but well-recognized immune-related adverse event (irAE), causes 35% of irAE related deaths. However, the mechanism of CIP remains unclear and no evidence-based treatment except for glucocorticoids is available. Herein, we report the case of a patient with metastatic bladder cancer who received tislelizumab and was diagnosed with CIP. The patient underwent transbronchial cryobiopsy. The patient was treated with glucocorticoid, but CIP recurred when the glucocorticoid tapering. The paraffine-embedded lung tissue was sectioned, stained with 31 heavy-metal tagged antibodies, and analyzed using imaging mass cytometry (IMC) technology. We identified multiple immune cell subsets in the lung tissue and observed the infiltration of memory T cells and the CD4 DC subset. The data indicated the great potential of IMC technology in the identification and characterization of irAEs. Further investigation is warranted to identify the mechanism of action of CIP.
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http://dx.doi.org/10.3389/fimmu.2022.899971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335486PMC
August 2022

Decoding transcriptional signatures of the association between free water and macroscale organizations in healthy adolescents.

Neuroimage 2022 Jul 25;261:119514. Epub 2022 Jul 25.

Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, PR China; Human Phenome Institute, Fudan University, Shanghai, PR China; Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China. Electronic address:

We leveraged a novel index of diffusion MRI to investigate the relationships among cortical free water, macro-organizations and gene expression in healthy adults. Few research has been conducted to investigate the role of free water in the healthy adults due to it can easily be affected also by aging diseases. High quality data of 350 subjects from Human Connectome Project were used in our study. Cortical free water was estimated by using a bi-tensor model. The free water was high in the limbic, insular and somatosensory cortex, while being lower in motor and association cortex. The negative correlation between the free water and cortical thickness has been consistently identified in almost all the cortical regions. Negative correlation between the cortical free water and structural covariance (rho=-0.38, p=0.005) revealed the free water was sensitive to cortical heterogeneity. Using human gene expression dataset, we found the gene expression pattern of the relationship between the free water and cortical thickness spatially coupled with primary gradient of structural covariance network (rho=0.40, p=0.004). Our findings indicated the free water was sensitive to the cortical cellular status. The relationship between free water and macroscale organization also reflected hierarchal structures of cerebral cortex.
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http://dx.doi.org/10.1016/j.neuroimage.2022.119514DOI Listing
July 2022

Modified constraint-induced movement therapy enhances cortical plasticity in a rat model of traumatic brain injury: a resting-state functional MRI study.

Neural Regen Res 2023 Feb;18(2):410-415

Center of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine; Institute of Rehabilitation Medicine, School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine; Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, China.

Modified constraint-induced movement therapy (mCIMT) has shown beneficial effects on motor function improvement after brain injury, but the exact mechanism remains unclear. In this study, amplitude of low frequency fluctuation (ALFF) metrics measured by resting-state functional magnetic resonance imaging was obtained to investigate the efficacy and mechanism of mCIMT in a control cortical impact (CCI) rat model simulating traumatic brain injury. At 3 days after control cortical impact model establishment, we found that the mean ALFF (mALFF) signals were decreased in the left motor cortex, somatosensory cortex, insula cortex and the right motor cortex, and were increased in the right corpus callosum. After 3 weeks of an 8-hour daily mCIMT treatment, the mALFF values were significantly increased in the bilateral hemispheres compared with those at 3 days postoperatively. The mALFF signal values of left corpus callosum, left somatosensory cortex, right medial prefrontal cortex, right motor cortex, left postero dorsal hippocampus, left motor cortex, right corpus callosum, and right somatosensory cortex were increased in the mCIMT group compared with the control cortical impact group. Finally, we identified brain regions with significantly decreased mALFF values at 3 days postoperatively. Pearson correlation coefficients with the right forelimb sliding score indicated that the improvement in motor function of the affected upper limb was associated with an increase in mALFF values in these brain regions. Our findings suggest that functional cortical plasticity changes after brain injury, and that mCIMT is an effective method to improve affected upper limb motor function by promoting bilateral hemispheric cortical remodeling. mALFF values correlate with behavioral changes and can potentially be used as biomarkers to assess dynamic cortical plasticity after traumatic brain injury.
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http://dx.doi.org/10.4103/1673-5374.344832DOI Listing
February 2023

Long non-coding RNA tumor protein 73 antisense RNA 1 influences an interaction between lysine demethylase 5A and promoter of tumor protein 73 to enhance the malignancy of colorectal cancer.

Hum Cell 2022 Sep 27;35(5):1512-1520. Epub 2022 Jul 27.

Gastrointestinal Cancer Ward, The third Department of Oncology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping district, Shenyang, 110004, Liaoning, People's Republic of China.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. The aim of the present study was to explore the expression level of tumor protein 73 (TP73) in highly malignant CRC tumors and how the long non-coding RNA tumor protein 73 antisense RNA 1 (TP73-AS1) influences that transcription. We found that TP73-AS1 was highly expressed in malignant CRC samples in The Cancer Genome Atlas (TCGA) database. We also demonstrated TP73-AS1 was expressed in thirty samples of CRC tissues collected from China Medical University patients as well as in HCT116, RKO and SW480 CRC cell lines but not in HCoEpiC or CCD-18Co normal colon cells. Only wild-type TP73-AS1, but not any of its alternate splicing isoforms, was positively correlated with tumor malignancy. TP73-AS1 transcripts were shown to be located in cell nuclei especially in close proximity to the TP73 promoter in CRC cells, but not in normal colon cells. In addition, an interaction between lysine demethylase 5A (KDM5A) and TP73-AS1 in CRC cells, but not normal colon cells, and KDM5A localization on the TP73 promoter were influenced by TP73-AS1. Interestingly, the H3K4me3 level on the TP73 promoter was reduced, but was elevated by TP73-AS1 knockdown in CRC cells. In conclusion, these results suggest a novel epigenetic role of TP73-AS1 on histone demethylation that influences TP73 transcription, and shed light on malignancy in CRC.
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http://dx.doi.org/10.1007/s13577-022-00740-2DOI Listing
September 2022

Ultralow Laser Power Three-Dimensional Superresolution Microscopy Based on Digitally Enhanced STED.

Biosensors (Basel) 2022 Jul 20;12(7). Epub 2022 Jul 20.

Shenzhen Key Laboratory of Photonics and Biophotonics, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China.

The resolution of optical microscopes is limited by the optical diffraction limit; in particular, the axial resolution is much lower than the lateral resolution, which hinders the clear distinction of the three-dimensional (3D) structure of cells. Although stimulated emission depletion (STED) superresolution microscopy can break through the optical diffraction limit to achieve 3D superresolution imaging, traditional 3D STED requires high depletion laser power to acquire high-resolution images, which can cause irreversible light damage to biological samples and probes. Therefore, we developed an ultralow laser power 3D STED superresolution imaging method. On the basis of this method, we obtained lateral and axial resolutions of 71 nm and 144 nm, respectively, in fixed cells with 0.65 mW depletion laser power. This method will have broad application prospects in 3D superresolution imaging of living cells.
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http://dx.doi.org/10.3390/bios12070539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351679PMC
July 2022

Genetic inhibition of PDK1 robustly reduces plaque deposition and ameliorates gliosis in the 5×FAD mouse model of Alzheimer's disease.

Neuropathol Appl Neurobiol 2022 Jul 26:e12839. Epub 2022 Jul 26.

MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China.

Aims: Abundant recent evidence has shown that 3-phosphoinositide-dependent protein kinase 1 (PDK1) is activated in Alzheimer's disease (AD). However, it remains unknown whether inhibition of PDK1 in neurons may affect AD-like pathology in animal models of AD. Here, we aim to examine the effects of specific inactivation of neuronal PDK1 on pathology and behaviour in 5×FAD mice and to identify the underlying molecular mechanisms.

Methods: The Cre-loxP system was employed to generate Pdk1 cKO/5×FAD mice, in which PDK1 is inactivated in excitatory neurons in the adult forebrain. Cellular and behavioural techniques were used to examine plaque burden, inflammatory responses and spatial working memory in mice. Biochemical and molecular analyses were conducted to investigate relevant mechanisms.

Results: First, Aβ deposition was massively decreased and gliosis was highly attenuated in Pdk1 cKO/5×FAD mice compared with 5×FAD mice. Second, memory deficits were significantly improved in Pdk1 cKO/5×FAD mice. Third, APP levels were notably decreased in Pdk1 cKO/5×FAD mice. Fourth, mammalian target of rapamycin (mTOR) signalling and ribosome biogenesis were reduced in Pdk1 cKO/5×FAD mice.

Conclusions: Neuron-specific deletion of PDK1 robustly ameliorates AD-like pathology and improves spatial working memory in 5×FAD mice. We propose that genetic approach to inhibit PDK1 may be an effective strategy to slow AD.
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http://dx.doi.org/10.1111/nan.12839DOI Listing
July 2022

Multiple B-Value Model-Based Residual Network (MORN) for Accelerated High-Resolution Diffusion-Weighted Imaging.

IEEE J Biomed Health Inform 2022 Jul 25;PP. Epub 2022 Jul 25.

Single-Shot Echo Planar Imaging (SSEPI) based Diffusion Weighted Imaging (DWI) has shortcomings such as low resolution and severe distortions. In contrast, Multi-Shot EPI (MSEPI) provides optimal spatial resolution but increases scan time. This study proposed a Multiple b-value mOdel-based Residual Network (MORN) model to reconstruct multiple b-value high-resolution DWI from undersampled k-space data simultaneously. We incorporated Parallel Imaging (PI) into a residual U-net to reconstruct multiple b-value multi-coil data with the supervision of MUltiplexed Sensitivity-Encoding (MUSE) reconstructed Multi-Shot DWI (MSDWI). Moreover, asymmetric concatenations among different b-values and the combined loss to back propagate helped the feature transfer. After training and validation of the MORN in a dataset of 32 healthy cases, additional assessments were performed on 6 patients with different tumor types. The experimental results demonstrated that the MORN model outperformed conventional PI reconstruction (i.e. SENSE) and two state-of-the-art deep learning methods (SENSE-GAN and VSNet) in terms of PSNR (Peak Signal-to-Noise Ratio), SSIM (Structual SIMilarity) and apparent diffusion coefficient maps. In addition, using the pre-trained model under DWI, the MORN achieved consistent fractional anisotrophy and mean diffusivity reconstructed from multiple diffusion directions. Hence, the proposed method shows potential in clinical application according to the observations on tumor patients as well as images of multiple diffusion directions.
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http://dx.doi.org/10.1109/JBHI.2022.3193299DOI Listing
July 2022

miR167d-ARFs Module Regulates Flower Opening and Stigma Size in Rice.

Rice (N Y) 2022 Jul 25;15(1):40. Epub 2022 Jul 25.

State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University, Chengdu, 611130, China.

Flower opening and stigma exertion are two critical traits for cross-pollination during seed production of hybrid rice (Oryza sativa L.). In this study, we demonstrate that the miR167d-ARFs module regulates stigma size and flower opening that is associated with the elongation of stamen filaments and the cell arrangement of lodicules. The overexpression of miR167d (OX167d) resulted in failed elongation of stamen filaments, increased stigma size, and morphological alteration of lodicule, resulting in cleistogamy. Blocking miR167d by target mimicry also led to a morphological alteration of the individual floral organs, including a reduction in stigma size and alteration of lodicule cell morphology, but did not show the cleistogamous phenotype. In addition, the four target genes of miR167d, namely ARF6, ARF12, ARF17, and ARF25, have overlapping functions in flower opening and stigma size. The loss-of-function of a single ARF gene did not influence the flower opening and stigma size, but arf12 single mutant showed a reduced plant height and aborted apical spikelets. However, mutation in ARF12 together with mutation in either ARF6, ARF17, or ARF25 led to the same defective phenotypes that were observed in OX167d, including the failed elongation of stamen filaments, increased stigma size, and morphological alteration of lodicule. These findings indicate that the appropriate expression of miR167d is crucial and the miR167d-ARFs module plays important roles in the regulation of flower opening and stigma size in rice.
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http://dx.doi.org/10.1186/s12284-022-00587-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314575PMC
July 2022

Radiogenomic analysis reveals tumor heterogeneity of triple-negative breast cancer.

Cell Rep Med 2022 Jul;3(7):100694

Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, No. 270 Dong'an Road, Shanghai 200032, China. Electronic address:

Triple-negative breast cancer (TNBC) is a subset of breast cancer with an adverse prognosis and significant tumor heterogeneity. Here, we extract quantitative radiomic features from contrast-enhanced magnetic resonance images to construct a breast cancer radiomic dataset (n = 860) and a TNBC radiogenomic dataset (n = 202). We develop and validate radiomic signatures that can fairly differentiate TNBC from other breast cancer subtypes and distinguish molecular subtypes within TNBC. A radiomic feature that captures peritumoral heterogeneity is determined to be a prognostic factor for recurrence-free survival (p = 0.01) and overall survival (p = 0.004) in TNBC. Combined with the established matching TNBC transcriptomic and metabolomic data, we demonstrate that peritumoral heterogeneity is associated with immune suppression and upregulated fatty acid synthesis in tumor samples. Collectively, this multi-omic dataset serves as a useful public resource to promote precise subtyping of TNBC and helps to understand the biological significance of radiomics.
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http://dx.doi.org/10.1016/j.xcrm.2022.100694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381418PMC
July 2022

Systematic simulation of the interactions of pleckstrin homology domains with membranes.

Sci Adv 2022 Jul 6;8(27):eabn6992. Epub 2022 Jul 6.

Astbury Centre for Structural and Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK.

Pleckstrin homology (PH) domains can recruit proteins to membranes by recognition of phosphatidylinositol phosphate (PIP) lipids. Several family members are linked to diseases including cancer. We report the systematic simulation of the interactions of 100 mammalian PH domains with PIP-containing membranes. The observed PIP interaction hotspots recapitulate crystallographic binding sites and reveal a number of insights: (i) The β1 and β2 strands and their connecting loop constitute the primary PIP interaction site but are typically supplemented by interactions at the β3-β4 and β5-β6 loops; (ii) we reveal exceptional cases such as the Exoc8 PH domain; (iii) PH domains adopt different membrane-bound orientations and induce clustering of anionic lipids; and (iv) beyond family-level insights, our dataset sheds new light on individual PH domains, e.g., by providing molecular detail of secondary PIP binding sites. This work provides a global view of PH domain/membrane association involving multivalent association with anionic lipids.
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http://dx.doi.org/10.1126/sciadv.abn6992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258823PMC
July 2022

Disrupted Topological Organization of White Matter Network in Angelman Syndrome.

J Magn Reson Imaging 2022 Jul 20. Epub 2022 Jul 20.

Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.

Background: Angelman syndrome (AS) is a genetic disorder that affects neurodevelopment. The investigation of changes in the brain white matter network, which would contribute to a better understanding of the pathogenesis of AS brain, was lacking.

Purpose: To investigate both local and global alterations of white matter in patients with AS.

Study Type: Prospective.

Subjects: A total of 29 AS patients (6.6 ± 1.4 years, 15 [52%] females) and 19 age-matched healthy controls (HC) (7.0 ± 1.5 years, 10 [53%] females).

Field Strength/sequence: A 3-T, three-dimensional (3D) T1-weighted imaging by using gradient-echo-based sequence, single shell diffusion tensor imaging by using spin-echo-based echo-planar imaging.

Assessment: Network metrics including global efficiency (E ), local efficiency (E ), small world coefficient (Swc), rich-club coefficient (Φ), and nodal degree (ND) were estimated from diffusion MR (dMR) data. Connections among highly connected (hub) regions and less connected (peripheral) regions were also assessed. Correlation between the topological parameters and age for each group was also calculated to assess the development of the brain.

Statistical Tests: Linear regression model, permutation test. P values estimated from the regression model for each brain region were adjusted by false discovery rate (FDR) correction.

Results: AS patients showed significantly lower E and higher swc compared to HC. Φ significantly increased at higher k-levels in AS patients. In addition, the connections among hub regions and peripheral regions were significantly interrupted in AS patients.

Data Conclusion: The AS brain showed diminished connectivity, reflected by reduced network efficiency compared to HC. Compared to densely connected regions, less connected regions were more vulnerable in AS.

Evidence Level: 2 TECHNICAL EFFICACY: Stage 3.
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http://dx.doi.org/10.1002/jmri.28360DOI Listing
July 2022

Photoactivation Properties of Self-n-Doped Perylene Diimides: Concentration-dependent Radical Anion and Dianion Formation.

ACS Mater Au 2022 Jul 22;2(4):482-488. Epub 2022 Apr 22.

Department of Chemistry, University of Utah, Salt Lake City, Utah 84112, United States.

Perylene diimides (PDIs) have garnered attention as organic photocatalysts in recent years for their ability to drive challenging synthetic transformations, such as aryl halide reduction and olefin iodoperfluoroalkylation. Previous work in this area employs spectator pendant groups attached to the imide nitrogen positions of PDIs that are only added to impart solubility. In this work, we employ electron-rich ammonium iodide or ammonium hydroxide pendant groups capable of self-n-doping the PDI core to form radical anions ( ) and dianions ( ). We observe formation is favored at low concentrations where aliphatic linkers are able to freely rotate, while formation is favored at elevated concentrations likely due to Coulombic stabilization between adjacent chromophores in a similar manner to that of Kasha exciton stabilization. Cyclic voltammetric measurements are consistent with steric encumbrance increasing the Lewis basicity of anions through Coulombic destabilization. However, sterics also inhibit dianion formation by disrupting aggregation. Finally, femtosecond transient absorption measurements reveal that low wavelength excitation (400 nm) preferentially favors the excitation of to the strongly reducing doublet excited state [ ]*. In contrast, higher wavelength excitation (520 nm) favors the formation of the singlet excited state []*. These findings highlight the importance of dopant architecture, counterion selection, excitation wavelength, and concentration on and formation, which has substantial implications for future photocatalytic applications. We anticipate these findings will enable more efficient systems based on self-n-doped PDIs.
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http://dx.doi.org/10.1021/acsmaterialsau.2c00019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284616PMC
July 2022

Psychological Resilience and Career Success of Female Nurses in Central China: The Mediating Role of Craftsmanship.

Front Psychol 2022 29;13:915479. Epub 2022 Jun 29.

Nursing Department of People's Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China.

Background: Nurses' career success is an important factor affecting the quality of nursing services and the stability of the nursing workforce, and enhancing nurses' career success level is of key significance to the development of the nursing discipline. As psychological resilience and craftsmanship are important spiritual traits in the process of nurses' career development, it is important to understand the mechanism of their effects on nurses' career success level.

Objective: To explore the current situation of craftsmanship, psychological resilience and career success levels of female nurses in central China, and to verify the mediating role of craftsmanship between psychological resilience and female career success using structural equation model.

Methods: A cross-sectional study was conducted among 2359 female nurses from three hospitals in central China through an online questionnaire, including craftsmanship, psychological resilience and career success scale. The data were analyzed by -test and Spearman rank correlation with SPSS 23.0 statistical software, and the mechanism of the effect of craftsmanship and psychological resilience on career success was completed by AMOS 23.0 statistical software.

Results: The scores of career success, psychological resilience, and craftsmanship of female nurses in central China were 68.00 (61.00, 75.00), 74.00 (64.00, 84.00), and 83.00 (79.00, 95.25). Spearman rank correlation analysis showed that Chinese female nurses' career success was positively correlated with craftsmanship ( = 0.511, < 0.01) and psychological resilience ( = 0.595, < 0.01). Craftsmanship played a mediating role between psychological resilience and career success, accounting for 39.3% of the total effect ratio.

Conclusion: The scores of career success and psychological resilience of female nurses in central China are at a moderate level, and craftsmanship plays a mediating role between psychological resilience and career success. It is suggested that nursing managers should pay attention to the importance of career success to nurses' self-development and nursing team stability, and improve their sense of career success by effectively improving nurses' psychological resilience and craftsmanship.
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http://dx.doi.org/10.3389/fpsyg.2022.915479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278649PMC
June 2022

Prognostic Value of Modified Model for End-Stage Liver Disease Score in Patients Undergoing Isolated Tricuspid Valve Replacement.

Front Cardiovasc Med 2022 1;9:932142. Epub 2022 Jul 1.

Department of Cardiovascular Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.

Objective: Though the prognostic value of the model for end-stage liver disease (MELD) score in tricuspid surgery was confirmed, the unstable international normalized ratio (INR) may affect the evaluation effectiveness of the MELD score for isolated tricuspid valve replacement (ITVR). The aim of the study was to assess the prognostic value of modified MELD for ITVR.

Methods And Results: A total of 152 patients who underwent ITVR were evaluated. The adverse outcome was defined as in-hospital mortality after surgery. The receiver operating characteristic (ROC) curve analysis demonstrated that a modified MELD score with albumin replacing INR (MELD-albumin) score presented well prognostic value [area under the curve (AUC) = 0.731, = 0.006] for in-hospital mortality. Through Cox regression and further interval validation, the MELD-albumin score was identified as an independent predictor for in-hospital mortality. The optimal cutoff value of MELD-albumin was identified as 8.58 through maximally selected log-rank statistics. In addition, restricted cubic spline analysis demonstrated the linear inverse relationship between MELD-albumin and hazard ratio (HR) for in-hospital mortality. Kaplan-Meier analysis illustrated that in-hospital mortality was increased significantly in the high MELD-albumin (MELD-albumin ≥8.58) group than in the low MELD-albumin group (MELD-albumin <8.58; < 0.001). Furthermore, high MELD-albumin was associated with lower body mass index (BMI), the incidence of lower extremities edema and moderate drinking history, and the MELD-albumin score was correlated with the value of aspartate transaminase (AST), alanine transaminase (ALT), and albumin. Furthermore, the incidence of renal failure ( = 0.003) and pulmonary infection ( = 0.042) was increased significantly in the high MELD-albumin group.

Conclusion: The MELD-albumin score could provide prognostic value for ITVR. In addition, the MELD-albumin score was useful in risk stratification and patient selection for patients with tricuspid regurgitation (TR) prior to ITVR.
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http://dx.doi.org/10.3389/fcvm.2022.932142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283717PMC
July 2022

ASO Visual Abstract: A Multiomics Signature Highlights Alterations Underlying Homologous Recombination Deficiency in Triple-Negative Breast Cancer.

Ann Surg Oncol 2022 Jul 15. Epub 2022 Jul 15.

Department of Radiology, Fudan University Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

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http://dx.doi.org/10.1245/s10434-022-12010-4DOI Listing
July 2022

Comparison of flash-free and conventional bonding systems: A systematic review and meta-analysis.

Angle Orthod 2022 Jul 14. Epub 2022 Jul 14.

Objectives: To review the literature systematically to compare the performance of adhesive precoated flash-free bonding systems with conventional adhesive precoated (APC) and operator-coated (OPC) bonding systems.

Materials And Methods: PubMed, Cochrane Library, Web of Science, and Embase were searched for potential eligible studies. Study selection and data collection were conducted independently. Statistical analysis was performed by Review Manager 5.3. The Cochran Q test was used to test heterogeneity in the included studies. Risk of bias was evaluated using Cochrane RoB 2.0 tool for randomized controlled trials.

Results: Six studies were included and the overall risk-of-bias judgment was low risk of bias to some concerns. The results of the meta-analyses showed that flash-free required significantly less bonding time than APC (mean difference [MD]: -1.56; 95% confidence intervals [CIs]: -2.56 to -0.56), and no significant differences were found in bond failure rates (risk ratio [RR]: 1.54; 95% Cis: 0.27 to 8.89) and adhesive remnant index (ARI) (MD: -0.50; 95% CIs: -1.14 to 0.14) between them. Qualitative analysis showed that flash-free might have a positive effect on enamel demineralization compared to APC but the quantity of plaque did not differ between them.

Conclusions: The flash-free bonding system significantly reduced bonding time and it had comparable bond failure rates with APC. So far, there is not enough evidence to support its positive effect on reducing enamel demineralization and the pathogenic bacteria around brackets. In summary, flash-free might be a better choice for clinical bracket bonding.
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http://dx.doi.org/10.2319/122221-932.1DOI Listing
July 2022

Morphological Changes of Frontal Areas in Male Individuals With HIV: A Deformation-Based Morphometry Analysis.

Front Neurol 2022 27;13:909437. Epub 2022 Jun 27.

Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China.

Objective: Previous studies on HIV-infected (HIV+) individuals have revealed brain structural alterations underlying HIV-associated neurocognitive disorders. Most studies have adopted the widely used voxel-based morphological analysis of T1-weighted images or tracked-based analysis of diffusion tensor images. In this study, we investigated the HIV-related morphological changes using the deformation-based morphometry (DBM) analysis of T1-weighted images, which is another useful tool with high regional sensitivity.

Materials And Methods: A total of 157 HIV+ (34.7 ± 8.5 years old) and 110 age-matched HIV-uninfected (HIV-) (33.7 ± 10.1 years old) men were recruited. All participants underwent neurocognitive assessments and brain scans, including high-resolution structural imaging and resting-state functional imaging. Structural alterations in HIV+ individuals were analyzed using DBM. Functional brain networks connected to the deformed regions were further investigated in a seed-based connectivity analysis. The correlations between imaging and cognitive or clinical measures were examined.

Results: The DBM analysis revealed decreased values (i.e., tissue atrophy) in the bilateral frontal regions in the HIV+ group, including bilateral superior frontal gyrus, left middle frontal gyrus, and their neighboring white matter tract, superior corona radiata. The functional connectivity between the right superior frontal gyrus and the right inferior temporal region was enhanced in the HIV+ group, the connectivity strength of which was significantly correlated with the global deficit scores ( = 0.214, = 0.034), and deficits in learning ( = 0.246, = 0.014) and recall ( = 0.218, = 0.031). Increased DBM indexes (i.e., tissue enlargement) of the right cerebellum were also observed in the HIV+ group.

Conclusion: The current study revealed both gray and white matter volume changes in frontal regions and cerebellum in HIV+ individuals using DBM, complementing previous voxel-based morphological studies. Structural alterations were not limited to the local regions but were accompanied by disrupted functional connectivity between them and other relevant regions. Disruptions in neural networks were associated with cognitive performance, which may be related to HIV-associated neurocognitive disorders.
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http://dx.doi.org/10.3389/fneur.2022.909437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271794PMC
June 2022

Carrying both COL1A2 and FBN2 gene heterozygous mutations results in a severe skeletal clinical phenotype: an affected family.

BMC Med Genomics 2022 07 8;15(1):154. Epub 2022 Jul 8.

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

Background: Osteogenesis imperfecta (OI) is the most common monogenic disease of the skeletal system and is usually caused by mutations in the COL1A1 or COL1A2 genes. Congenital contractural arachnodactyly syndrome (CCA) is an autosomal dominant hereditary disease of connective tissue. To date, the FBN2 gene is the only gene reported to cause CCA. Researchers found that COL1A2 and FBN2 are both involved in the extracellular matrix organization pathway. These findings suggest that these two genes play an important role in a similar mechanism and may trigger a synergistic effect.

Methods: Trio-whole-exome sequencing (Trio-WES) was performed to analyse the underlying genetic cause of a proband with OI in a Chinese family. Sanger sequencing was used to validate the mutations in 3 members of the family with OI with varying degrees of severity of skeletal abnormalities and the members with no clinical signs.

Result: A c.3304G > C mutation in the COL1A2 gene (p.Gly1102Arg) and a novel c.4108G > T mutation in the FBN2 gene (p.Glu1370*) were detected in the proband, an affected member of the family. The affected individuals with both mutations present a more severe phenotype, while affected individuals present a milder phenotype if only the mutation in COL1A2 is detected (c.3304G > C). The unaffected individual in this family did not have any mutations in the COL1A2 gene or FBN2 gene.

Conclusion: Our study is the first clinical report to indicate that patients carrying concomitant mutations in both the COL1A2 and FBN2 genes may present with more severe skeletal abnormalities. Furthermore, our study suggests the possibility of synergistic effects between the COL1A2 and FBN2 genes.
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http://dx.doi.org/10.1186/s12920-022-01296-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9270787PMC
July 2022

Circulating cytokine profile and modulation of regulatory T cells in chronic hepatitis B patients with type 2 diabetes mellitus.

Bosn J Basic Med Sci 2022 Jul 7. Epub 2022 Jul 7.

Department of Endocrinology, Xi'an No.1 Hospital, Xi'an, Shaanxi Province, China.

The risk of hepatitis B virus (HBV) infection is higher in patients with diabetes mellitus, and diabetes mellitus is one of the metabolic complications of HBV infection. However, the cytokine profile of chronic hepatitis B (CHB) patients with type 2 diabetes mellitus (T2DM) is not fully understood. The aim of this study was to investigate the cytokine expression profile in CHB patients with T2DM, and to assess the regulatory function of cytokines to regulatory T cells (Tregs). Forty-four T2DM patients, 39 CHB patients, 17 patients with CHB and T2DM, and 21 control subjects were enrolled. Cytokine levels in the plasma were measured by Luminex multiplex assay. CD4+CD25+CD127dim/- Tregs were detected by flow cytometry. Tregs were purified and stimulated with recombinant human interleukin-15 (IL-15). The regulation of IL-15 on Tregs function was investigated by measuring cell number, IL-10/IL-35 secretion, and mRNA expression of immune checkpoint molecules in a Tregs+PBMC co-culture system. We found that levels of IL-1α, IL-6, and IL-33 were upregulated, while IFN-α, IL-2, IL-7, and IL-15 were downregulated in T2DM and CHB patients. CHB patients with T2DM had even lower plasma IL-7 and IL-15 levels. Tregs percentage was elevated in T2DM and CHB patients. CHB patients with T2DM had increased levels of Tregs, which correlated negatively with IL-15. Tregs showed stronger inhibitory activity in CHB patients with T2DM than in controls, T2DM, and CHB patients, which presented as reduction in cellular proliferation and induction of IL-10/IL-35 secretion. IL-15 suppressed Tregs function and inhibited the expression of immune checkpoint molecules in Tregs. The current data suggest that insufficient IL-15 levels and decreased responsiveness of Tregs to IL-15 signaling might contribute to strong immune dysfunction in CHB patients with T2DM.
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http://dx.doi.org/10.17305/bjbms.2022.7525DOI Listing
July 2022
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