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UHRF1 as a member of RING-finger type E3 ubiquitin ligases family, is an epigenetic regulator with five structural domains. It has been involved in the regulation of a series of biological functions, such as DNA replication, DNA methylation, and DNA damage repair. Additionally, aberrant overexpression of UHRF1 has been observed in ove r ten cancer types, indicating that UHRF1 is a typical oncogene. The overexpression of UHRF1 repressed the transcription of such tumor-suppressor genes as CDKN2A BRCA1 and CDH1 through DNMT1-mediated DNA methylation. In addition to the upstream transcription factors regulating gene transcription, post-translational modifications (PTMs) also contribute to abnormal overexpression of UHRF1 in cancerous tissues. The types of PTM include phosphorylation, acetylation, methylationand ubiquitination, which regulate protein stability, histone methyltransferase activity, intracellular localization and the interaction with binding partners. Recently, several novel PTM types of UHRF1 have been reported, but the detailed mechanisms remain unclear. This comprehensive review summarized the types of UHRF1 PTMs, as well as their biological functions. A deep understanding of these crucial mechanisms of UHRF1 is pivotal for the development of novel UHRF1-targeted anti-cancer therapeutic strategies in the future.

Jian Jiang,1,2,* Xiaoyan Hou,1,* Lili Gu,3 Xian Liu,1 Huiting Lv,1 Jiaxin Xiong,1 Hongmei Kuang,1,2 Xiaofeng Jiang,1 Shunda Hong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, People’s Republic of China; 2Jiangxi Medical Imaging Research Institute, Nanchang, People’s Republic of China; 3Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shunda Hong, Department of Radiology, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86-791-88693825, Email dyfy05441@ncu.edu.cnPurpose: This study aimed to explore the abnormal changes in short- and long-range functional connectivity density (FCD) in patients with herpes zoster (HZ) and postherpetic neuralgia (PHN).Patients and Methods: Twenty HZ patients, 22 PHN patients, and 19 well-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging scans. We used FCD mapping, a data-driven graph theory method, to investigate local and global functional connectivity patterns. Both short- and long-range FCD were calculated and compared among the PHN, HZ, and HC groups. Then, the abnormal regions were used to calculate seed-based functional connectivity. Finally, correlation analyses were performed between the altered FCD values and clinical datas.Results: Compared with HCs, HZ patients showed significantly increased long-range FCD of the bilateral cerebellum, thalamus, parahippocampal gyrus, superior temporal gyrus and lingual gyrus. HZ patients also displayed significantly decreased short-range FCD of the bilateral posterior cingulate gyrus, median cingulate/paracingulate gyri, and left precuneus. Compared with HCs, PHN patients displayed significantly decreased long-range FCD of the bilateral superior frontal gyrus and de

Xian Liu,1,* Lili Gu,2,* Jiaqi Liu,3 Shunda Hong,1 Qing Luo,1 Ying Wu,1 Jiaojiao Yang,1 Jian Jiang1 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Radiology, The Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi, 330006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Jiang, Department of Radiology, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, People’s Republic of China, Tel +86 791 8869 3825, Email jij2002cn@126.comObjective: To measure the changes in cerebral cortical thickness in patients with herpes zoster (HZ) and postherpetic neuralgia (PHN) by surface-based morphometry (SBM) and further estimate its correlation with clinical scores.Materials and Methods: Twenty-nine HZ patients, 30 PHN patients and 30 well-matched healthy controls (HCs) were included. Magnetic resonance imaging (MRI) data from all subjects were collected and then analyzed by SBM. The changes in cortical thickness among the HZ, PHN and HC groups were analyzed by ANOVA and correlated with clinical scores.Results: The thickness of the bilateral primary visual cortex (V1, V2) and right primary visual cortex (V3), left somatosensory cortex (L3A), right anterior cingulate gyrus and medial prefrontal cortex (RS32) increased in PHN group, and the thickness the left insular and frontal opercular cortex (LFOP4), left motor cortex (L3B), and right superior temporal visual cortex (RSTV) were decreased in the HZ and PHN groups compared to the HC group. The thickness measurements of RS32, LFOP4, and (L3B) in HZ and PHN patients were correlated with the duration of disease. In HZ and PHN patients, the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Sc

This paper offers an extensive review of publications dealing with the modeling, the design and the experimental investigation of grooved dynamic gas lubricated bearings. Recent years have witnessed a rise in small-scale and high-speed turbomachinery applications. Besides the well-known gas foil bearings, grooved bearings offer attractive advantages, which unveil their potential in particular at small scale due to the structural simplicity as well as satisfying predictability. This paper starts with a general background of the application of gas lubricated bearings and introduces and compares the different gas bearing topologies. Further, the state-of-the-art modeling of grooved gas lubricated bearings is introduced in a systematic way assessing the advantages and inconveniences of two major approaches, the Narrow Groove Theory (NGT) and direct discretization method. Since NGT method is an elegant and efficient approach to model the complex effects of periodic grooves, a critical section is dedicated to the Narrow Groove Theory. In a second phase different models to include additional physical phenomena such as real gas lubrication, rarefaction or turbulence effects are reviewed. The paper concludes with a critical assessment of the state-of-the-art and indicates potential fields of research that would allow to shed more light into the understanding of these bearings, as well as with some thoughts on the integrated design methodologies of gas bearing supported rotors.

This paper offers an extensive review of publications dealing with the modeling, the design and the experimental investigation of grooved dynamic gas lubricated bearings. Recent years have witnessed a rise in small-scale and high-speed turbomachinery applications. Besides the well-known gas foil bearings, grooved bearings offer attractive advantages, which unveil their potential in particular at small scale due to the structural simplicity as well as satisfying predictability. This paper starts with a general background of the application of gas lubricated bearings and introduces and compares the different gas bearing topologies. Further, the state-of-the-art modeling of grooved gas lubricated bearings is introduced in a systematic way assessing the advantages and inconveniences of two major approaches, the Narrow Groove Theory (NGT) and direct discretization method. Since NGT method is an elegant and efficient approach to model the complex effects of periodic grooves, a critical section is dedicated to the Narrow Groove Theory. In a second phase different models to include additional physical phenomena such as real gas lubrication, rarefaction or turbulence effects are reviewed. The paper concludes with a critical assessment of the state-of-the-art and indicates potential fields of research that would allow to shed more light into the understanding of these bearings, as well as with some thoughts on the integrated design methodologies of gas bearing supported rotors.

Jiaqi Liu,1,* Lili Gu,2,* Qing Huang,1 Shunda Hong,1 Xianjun Zeng,1 Daying Zhang,2 Fuqing Zhou,1 Jian Jiang1 1Department of Radiology, 2Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this study was to measure brain alterations in patients with herpes zoster (HZ) and postherpetic neuralgia (PHN) and compare their differences using a voxel-based morphometry (VBM) technique. Materials and methods: Thirty-three patients with HZ, 22 patients with PHN, and 28 well-matched healthy controls (HCs) were recruited. Magnetic resonance imaging data were acquired for all subjects and analyzed using the VBM method. The changes in gray matter volume (GMV) in HZ and PHN groups were compared with those in HC group, and the GMV differences were also compared between the PHN and HZ groups. Further correlation analysis and receiver operating characteristic curves were used to confirm the significance of GMV changes in various brain regions. Results: Compared with HCs, decreased GMV was found in the bilateral insular lobes and increased GMV was found in the bilateral thalamus in the HZ group. In the PHN group, GMV decreased in the bilateral insula lobes, right middle frontal gyrus, bilateral precentral gyrus, and left postcentral gyrus and increased in the left cerebellar posterior lobe, right parahippocampal gyrus, and right lentiform nucleus. In addition, the PHN group exhibited increased GMV in the left cerebellar tonsil, culmen, and left lentiform nucleus and decreased GMV in the right precentral gyrus compared with the HZ group. Further correlation analysis and receiver operating characteristic curves revalidate the significance of most of these abnormal brain regions. Conclusion: The VBM method revealed widespread GMV abnormalities in HZ and PHN patients. The brains of PHN patients have broader abnormalities in nonpain-related regions

Lili Gu,1,* Shunda Hong,2,* Jian Jiang,2 Jiaqi Liu,2 Xintian Cao,1 Qing Huang,2 Xianjun Zeng,2 Fuqing Zhou,2 Daying Zhang1 1Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China 2Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Purpose: Postherpetic neuralgia (PHN) detrimentally affects brain function. Recent studies have suggested that frequency-dependent changes in electroencephalography in chronic pain patients and blood oxygenation level dependent (BOLD) fluctuations can reflect neuronal activity in different frequencies. The current study aimed to investigate PHN-related brain oscillatory activity in a specific frequency band by using the amplitude of low-frequency fluctuation (ALFF) method.Materials and methods: ALFF changes were analyzed across different frequencies (slow-4 band: 0.027–0.073 Hz; slow-5 band: 0.01–0.027 Hz; and typical band: 0.01–0.08 Hz) in the brains of PHN patients and compared with those in the brains of healthy controls (HCs) during resting-state fMRI. Eighteen HCs and PHN patients underwent fMRI scanning.Results: In the typical band, compared with HCs, PHN patients showed prominently decreased ALFF in the right prefrontal cortex (Brodmann area 10/46) and increased ALFF in the bilateral brain stem/cerebellum anterior lobe (BS/CAL). In the slow-4 band, PHN patients exhibited significantly decreased ALFF in the bilateral cuneus/lingual gyrus and the right prefrontal cortex. In the slow-5 band, PHN patients presented significantly increased ALFF in the bilateral BS/CAL and left parieto-occipital cortex. Moreover, the increased ALFF in the left parieto-occipital cortex in the slow-5 band was positively correlated with VAS scores (P=0.022), and the increased ALFF in the bilateral BS/CAL in the slow-5 band was po

Shunda Hong,1,* Lili Gu,2,* Fuqing Zhou,1 Jiaqi Liu,1 Muhua Huang,1 Jian Jiang,1 Laichang He,1 Honghan Gong,1 Xianjun Zeng1 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this study was to explore intrinsic functional connectivity patterns in patients with herpes zoster (HZ) and postherpetic neuralgia (PHN). Patients and methods: Thirty-three right-handed HZ patients (13 males; mean age 57.15±9.30 years), 22 right-handed PHN patients (9 males; mean age 66.13±6.77 years), and 28 well-matched healthy controls (HC) (9 males; mean age 54.21±7.72 years) underwent resting-state functional magnetic resonance imaging for intrinsic functional connectivity analyses. Functional connectivity density (FCD) was calculated and compared among the PHN, HZ, and HC groups. In addition, the Pearson correlation coefficient was calculated to compare various clinical indices in the regions with abnormal FCD values. Results: Compared with the HC, both HZ and PHN patients showed significantly decreased FCD in the precuneus, and patients with HZ displayed significantly increased FCD in the brainstem/limbic lobe/parahippocampalgyrus, whereas patients with PHN displayed significantly increased FCD in the hippocampus (correlation thresholds r=0.25, voxel level of P<0.01 and Gaussian random field theory at a cluster level of P<0.05). However, the FCD was not significantly different between the PHN and HZ patients. Furthermore, the decreased FCD in the precuneus was positively correlated with the visual analog scale score in the PHN group (r=0.672; P=0.001). Conclusion: Decreased connectivity of the precuneus occurred in both HZ and PHN patients, indicating a disrupted d

Fuqing Zhou,1,2 Lili Gu,3 Shunda Hong,1,2 Jiaqi Liu,1,2 Jian Jiang,1,2 Muhua Huang,1,2 Yong Zhang,3 Honghan Gong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Neuroradiology Laboratory, Jiangxi Province Medical Imaging Research Institute, Nanchang, Jiangxi, People’s Republic of China; 3Department of Pain Clinic, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China Objective: The aim of this study was to explore the amplitude of intrinsic low-frequency oscillations (LFOs) in patients with discogenic low-back and leg pain (LBLP).Participants and methods: We obtained and compared the LFO amplitude from 25 right-handed discogenic LBLP patients (13 males; mean age 55.16±1.83 years) and 27 well-matched healthy controls (15 males; mean age 52.96±1.63 years). The LFO amplitude was examined using the voxel-wise amplitude of low-frequency fluctuations (ALFFs), and partial correlation analysis was performed to determine the relationship between the regions with altered ALFF values and clinical parameters in discogenic LBLP patients.Results: Compared with healthy controls, the patients with discogenic LBLP showed a significant increase in ALFF in the affective system of the pain matrix (left anterior cingulate cortex, right anterior insula/frontal operculum, and bilateral orbitofrontal cortex) and information-processing regions (middle occipital/temporal gyrus). In addition, a significant decrease in ALFF was observed in the default mode network (DMN; inferior parietal lobule (IPL) and medial prefrontal cortex [mPFC]) and the processing system of the pain matrix (basal ganglia/thalamus/midbrain, postcentral gyrus [PoCG], and fusiform gyrus). Several regions with altered ALFF were associated with disease duration, visual analog scale scores, Barthel index, and fine sensory modality me

The human DEAD-box helicase 3 (DDX3) has been shown to contribute to type I interferon induction downstream of anti-viral pattern recognition receptors (PRRs). It binds to TANK-binding kinase 1 (TBK1) and IB-kinase- (IKK, the two key kinases mediating activation of Interferon regulatory factor (IRF) 3 and IRF7. We previously demonstrated that DDX3 facilitates IKK activation downstream of RIG-I and then links the activated kinase to IRF3. In this study, we probed the interactions between DDX3 and other key signalling molecules in the RIG-I pathway and identified a novel direct interaction between DDX3 and TRAF3 mediated by a TRAF-interaction motif in the N-terminus of DDX3, which was required for TRAF3 ubiquitination. Interestingly, we observed two waves of K63-linked TRAF3 ubiquitination following RIG-I activation by Sendai Virus infection (SeV), both of which were suppressed by DDX3 knockdown. We also investigated the spatiotemporal formation of endogenous downstream signalling complexes containing the MAVS adaptor, DDX3, IKK, TRAF3 and IRF3. DDX3 was recruited to MAVS early after SeV infection, suggesting it might mediate subsequent recruitment of other molecules. Indeed, knockdown of DDX3 prevented formation of TRAF3-MAVS and TRAF3-IKKcomplexes. Based on our data, we propose that early TRAF3 ubiquitination is required for formation of a stable MAVS-TRAF3 complex, while the second wave of TRAF3 ubiquitination mediates IRF3 recruitment and activation. Our study characterises DDX3 as a multifunctional adaptor molecule that coordinates assembly of different TRAF3, IKK and IRF3-containing signalling complexes downstream of MAVS. Additionally, it provides novel insights into the role of TRAF3 in RIG-I signalling.

The human DEAD-box helicase 3 (DDX3) has been shown to contribute to type I interferon induction downstream of anti-viral pattern recognition receptors (PRRs). It binds to TANK-binding kinase 1 (TBK1) and IB-kinase- (IKK, the two key kinases mediating activation of Interferon regulatory factor (IRF) 3 and IRF7. We previously demonstrated that DDX3 facilitates IKK activation downstream of RIG-I and then links the activated kinase to IRF3. In this study, we probed the interactions between DDX3 and other key signalling molecules in the RIG-I pathway and identified a novel direct interaction between DDX3 and TRAF3 mediated by a TRAF-interaction motif in the N-terminus of DDX3, which was required for TRAF3 ubiquitination. Interestingly, we observed two waves of K63-linked TRAF3 ubiquitination following RIG-I activation by Sendai Virus infection (SeV), both of which were suppressed by DDX3 knockdown. We also investigated the spatiotemporal formation of endogenous downstream signalling complexes containing the MAVS adaptor, DDX3, IKK, TRAF3 and IRF3. DDX3 was recruited to MAVS early after SeV infection, suggesting it might mediate subsequent recruitment of other molecules. Indeed, knockdown of DDX3 prevented formation of TRAF3-MAVS and TRAF3-IKKcomplexes. Based on our data, we propose that early TRAF3 ubiquitination is required for formation of a stable MAVS-TRAF3 complex, while the second wave of TRAF3 ubiquitination mediates IRF3 recruitment and activation. Our study characterises DDX3 as a multifunctional adaptor molecule that coordinates assembly of different TRAF3, IKK and IRF3-containing signalling complexes downstream of MAVS. Additionally, it provides novel insights into the role of TRAF3 in RIG-I signalling.

Jian Jiang,1,* Lili Gu,2,* Dan Bao,2 Shunda Hong,1 Wei He,1 Yonming Tan,1 Xianjun Zeng,1 Honghan Gong,1 Daying Zhang,2 Fuqing Zhou1 1Department of Radiology, 2Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Objective: The aim of this study was to explore interhemispheric intrinsic connectivity in patients with postherpetic neuralgia (PHN). Methods: We obtained resting-state functional magnetic resonance imaging data from 18 right-handed PHN patients (11 males, 7 females; mean age, 59.67±8.41 years) and 18 well-matched healthy controls (11 males, 7 females; mean age, 38.50±7.51 years). Interhemispheric connectivity was examined using voxel-mirrored homotopic connectivity (VMHC), and seed-based functional connectivity analysis was performed. Results: Compared with the healthy controls, the patients with PHN showed abnormally decreased homotopic connectivity in the dorsolateral prefrontal cortex and the precuneus and posterior cingulate cortex (PCUN/PCC). The decreased VMHC in the PCUN/PCC was positively correlated with the visual analog scale of PHN in the PHN patient group (p=0.651; P=0.006). Receiver operating characteristic (ROC) analysis revealed that the areas under the curves for the two brain regions were 0.898 for the prefrontal cortex and 0.923 for the PCUN/PCC, which indicated that the VMHC could be used to discriminate PHN patients from healthy controls. A subsequent seed-based functional connectivity analysis revealed widely disrupted intrinsic connectivity between the regions that showed local homotopic connectivity deficits and the areas subserving the default-mode network. Conclusion: Our results indicated reduced interhemispheric functional connectivity in patients with PHN, which seems to be an important new avenue to investigate to better understand the nature of disconnection of the functional architec