Publications by authors named "Cong Han"

127 Publications

Proteomic Profiling of Exosomes From Hemorrhagic Moyamoya Disease and Dysfunction of Mitochondria in Endothelial Cells.

Stroke 2021 Aug 2:STROKEAHA120032297. Epub 2021 Aug 2.

Department of Neurosurgery, The Fifth Medical Centre of PLA General Hospital, Beijing, China (C.H., L.D.).

Background And Purpose: Moyamoya disease (MMD) is a rare steno-occlusive and slowly progressing cerebrovascular disorder. The detailed mechanism of the underlying pathogenesis is still blurry.

Methods: Tandem Mass Tag-labeled quantitative proteomics was performed on serum-derived exosomes (SDEs) extracted from adult patients diagnosed with pure ischemic MMD or hemorrhagic MMD and healthy controls. Then mouse brain vascular endothelial cell (EC), human umbilical vein EC, neuroblastoma cell, and human hepatocyte cell were treated with exosomes, and changes of the protein expression in mouse brain vascular EC cells were identified.

Results: Proteomics analysis results showed that 859 shared proteins were detected in SDEs from ischemic and hemorrhagic MMD patients with 231 differently expressed compared with healthy controls. Bioinformatic analysis revealed dysregulated cell growth and maintenance and indicated disturbed actin dynamics in MMD, with CFL1 (Cofilin-1) and ACTR2/3 (actin-related protein 2/3; also known as ARP2/3) downregulated in ischemic and hemorrhagic patients' SDEs. We also found immunity dysfunction in hemorrhagic MMD. Following treatment with MMD SDEs, mouse brain vascular EC cells showed significantly higher levels of proliferation and more ethynyl-2-deoxyuridine-positive cells compared with the healthy control group, while there were no obvious changes in the human umbilical vein EC and human hepatocyte cell. Interestingly, we also found that SDEs from ischemic MMD promoted neuroblastoma cell proliferation. Proteomic analysis of mouse brain vascular EC cells suggested that SDEs from hemorrhagic MMD patients induced dysfunction of the mitochondria in cerebrovascular ECs.

Conclusions: This study highlighted potential molecular mechanisms underlying the pathogenesis of MMD patients, thereby providing new therapeutic strategies for MMD.
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http://dx.doi.org/10.1161/STROKEAHA.120.032297DOI Listing
August 2021

Partitioning of evapotranspiration and the influencing factors of evapotranspiration components in a shrub ecosystem dominated by and var. in the Mu Us Desert, Northwest China.

Ying Yong Sheng Tai Xue Bao 2021 Jul;32(7):2407-2414

School of Soil and Water Conservation, Beijing Forestry University, Beijing 100083, China.

Evapotranspiration (ET) is an important part of water cycle and energy flow in ecosystem. Accurate estimation of ET and its components is critical for understanding the impacts of ecophysiological processes on ecosystem water balance and plant water use strategy. Using the eddy-covariance technique and the micro-lysimeter, we measured ET, evaporation (), transpiration () of the - var. shrubland in the Mu Us Desert during May 20 to September 15, 2019, quantified the ET components, and analyzed the seasonal characteristics and influencing factors of ET and its components. The results showed that was the main component of ET in the growing season, with a /ET of 53.1%. /ET increased and /ET decreased as precipitation decreased. The partitioning of evapotranspiration was regulated by precipi-tation. At the seasonal scale, the value of was positively correlated with soil water content at 10 cm depth (SWC) and net radiation (), while SWC was the main factor influencing . The value of increased with the increases of and leaf area index (LAI), and increased first and then decreased with the increases of soil water content at 30 cm layer (SWC). was affected by SWC, and LAI. Moisture was the main influencing factor of ET. The ET/ in the growing season was 109.2% and was 250.5% in May, indicating that the water consumption of ET in early growing season was partly from the precipitation in non-growing season.
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http://dx.doi.org/10.13287/j.1001-9332.202107.015DOI Listing
July 2021

Assessment of the hydrochemistry, water quality, and human health risk of groundwater in the northwest of Nansi Lake Catchment, north China.

Environ Geochem Health 2021 Jun 15. Epub 2021 Jun 15.

801 Institute of Hydrogeology and Engineering Geology, Shandong Provincial Bureau of Geology & Mineral Resources, Jinan, 250014, China.

In this study, the formation mechanism and water quality of groundwater in the northwest of Nansi Lake Catchment (NNLC) were analyzed through mathematical statistics, hydrochemical analysis and entropy weighted water quality index (EWQI), and the human health risk of nitrate was also evaluated. To this end, 89 wells in the NNLC were sampled, and the groundwater samples were divided into three groups (I, II, and III) according to cluster analysis results and spatial distribution. The main results are as follows: Topographically, Groups I, II, and III correspond to the alluvial plains, apron plain, and low hills and its front margin, respectively. According to the Piper diagram, the hydrochemical types of Groups I and II groundwater are Na-SO·Cl and Ca·Mg-HCO, respectively, and that of Group III is more concentrated, mostly corresponding to the Ca-HCO type. Hydrochemical analysis indicated that the development of groundwater hydrochemistry is mainly attributable to water-rock interactions, with the primary process being the dissolution of minerals such as calcite, dolomite, gypsum, and albite. Evaporation exhibited an increasing trend from the northeast to the southwest. Groups I and III presented obvious effects of human activities, with Group I showing sulfate pollution and Group III mainly showing nitrate pollution. Analysis of the characteristics and causes of the groundwater hydrochemistry revealed the proposed approach has excellent performance for classification in areas with complex hydrogeological conditions. The results of EWQI showed that the overall water quality was good, following the order Group III > Group II > Group I. The overall human health risk of nitrate in groundwater was low, but the risk was slightly higher for children than for adults. Therefore, the effects of nitrate contamination should be considered when exploiting hilly and peri-urban groundwater for drinking water.
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http://dx.doi.org/10.1007/s10653-021-01011-zDOI Listing
June 2021

The effects of extruded endogenous starch on the processing properties of gluten-free Tartary buckwheat noodles.

Carbohydr Polym 2021 Sep 7;267:118170. Epub 2021 May 7.

State Key Laboratory of Food Science and Technology, Jiangnan University, 1800, Lihu Avenue, Wuxi 214122, Jiangsu Province, PR China; School of Food Science and Technology, Jiangnan University, 1800 Lihu Avenue, Wuxi 214122, Jiangsu Province, PR China; Qingdao Special Food Research Institute, Qingdao 266109, Shandong Province, PR China. Electronic address:

The lack of gluten in Tartary buckwheat has always been the main limiting factor of their development. This paper explored how to improve the processing quality of gluten-free Tartary buckwheat noodles (GF-TBNs) by introducing extruded starch into Tartary buckwheat flour (TBF) and the underlying mechanism was also elucidated. Extruded Tartary buckwheat starch (ETBS) was obtained under different extrusion conditions. The thermal properties, molecular weight, and viscosity of ETBS were examined to determine the key parameters closely related to the water distribution and rheological properties of the dough sheet, and tensile properties of GF-TBNs. The results showed that ETBS with a low molecular weight and high viscosity contributed greatly to the GF-TBNs with good tensile properties. It is proposed that ETBS with a low molecular weight and high viscosity might form a gel-entrapped network inside GF-TBNs, which was confirmed by the morphology of GF-TBNs.
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http://dx.doi.org/10.1016/j.carbpol.2021.118170DOI Listing
September 2021

Assessment of the water quality of groundwater in Bohai Rim and the controlling factors-a case study of northern Shandong Peninsula, north China.

Environ Pollut 2021 May 29;285:117482. Epub 2021 May 29.

College of Energy and Mining Engineering, Shandong University of Science and Technology, Qingdao, Shandong, 266590, China. Electronic address:

This study collected 184 groundwater (GW) samples from 92 wells during the dry and wet seasons, respectively to understand the hydrochemical characteristics, water quality, and risk of GW nitrate (NO) to human health in northern Shandong Peninsula (NSP), China. The results showed that GW in the NSP is weakly alkaline and classified as hard fresh water. The mean concentration of NO in GW exceeded 100 mg·L, total hardness exceeded 450 mg·L, and total dissolved solids (TDS) was less than 1000 mg·L. A Piper diagram showed that the water chemistry of GW in the NSP was mainly of the SO·Cl-Ca·Mg type. A Gibbs diagram and ion ratio analysis indicated that the weathering of silicate rocks and agricultural production were the dominant factors affecting the hydrochemical characteristics of GW in the NSP, with cation exchange, dissolution of salt rock, and weathering of carbonate rock also making contributions. Na and Cl in GW are significantly affected by seawater aerosols in coastal areas. During the wet season, the hydrodynamic conditions of the aquifer are improved, agricultural activities are strengthened, and GW becomes generally homogenized. The water quality index classified the GW quality of the NSP as mainly of medium quality. There was a relatively consistent spatial distribution of water quality during different periods. Water samples of poor water quality were mainly distributed in the lower reaches of the Huangshui River. In addition, total hardness and NO concentrations were the main variables affecting the quality of GW in the NSP. The assessment of the risk NO in GW in the NSP to human health through the ingestion of drinking water demonstrated a significant risk (infants > children > adults). These results indicate the need for local management measures to reduce the potential health risks of GW quality in the NSP.
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http://dx.doi.org/10.1016/j.envpol.2021.117482DOI Listing
May 2021

Photoluminescence, optical transition properties and temperature-induced shift of charge transfer band and temperature sensing property of GdNbTiO: Sm phosphors.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Nov 12;260:119951. Epub 2021 May 12.

School of Science, Dalian Maritime University, Dalian, Liaoning 116026, PR China. Electronic address:

GdNbTiO: Sm phosphors with various Sm concentrations were prepared via a high temperature solid-state reaction method. The crystal structure of the samples was characterized by means of X-ray diffraction (XRD) and the as-prepared samples were confirmed to be orthorhombic phase GdNbTiO. Photoluminescence properties were investigated by measuring the concentration- and temperature-dependent photoluminescence spectra. Concentration-dependent luminescence quenching and luminescent thermal quenching behaviors were observed and they were respectively ascribed to the electric dipole-dipole interaction between Sm ions and the cooperation of energy transfer and crossover process. The chromatic characteristics were found to be dependent on the excitation wavelength and Sm concentration. In addition, temperature-induced redshift of charge transfer band of GdNbTiO host was found in temperature-dependent excitation spectra and the opposite variations of different excitation peaks were utilized for optical thermometry. Finally, the optical transition property was studied on the basis of the diffuse reflectance spectra and Judd-Ofelt (J-O) theory, meanwhile, its accuracy was evaluated by the result of emission spectra.
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http://dx.doi.org/10.1016/j.saa.2021.119951DOI Listing
November 2021

Clinical and Genetic Risk Factors of Long-Term Outcomes after Encephaloduroarteriosynangiosis in Moyamoya Disease in China.

J Stroke Cerebrovasc Dis 2021 Jul 13;30(7):105847. Epub 2021 May 13.

Department of Neurosurgery, The Fifth Medical Centre, Chinese PLA General Hospital (Former 307th Hospital of the PLA), Beijing China. Electronic address:

Objectives: This retrospective study was conducted to analyze the associations between ring finger protein 213 p.R4810K variant, clinical features and long-term outcomes in patients with moyamoya disease (MMD) after encephaloduroarteriosynangiosis treatment.

Materials And Methods: A total of 2,545 patients with MMD in China were included in this study (median of follow-up duration: 32.00 months). Multiple Cox regression models were used to assess the associations between p.R4810K variant, clinical features and long-term outcomes.

Results: For all patients, in multivariate Cox analysis, no association was observed between p.R4810K and long-term outcomes. Pediatric onset (HR, 0.38; 95%CI, 0.25-0.59) and headache (HR, 0.26; 95%CI, 0.08-0.83) were inversely and hypertension (HR, 1.43 95%CI, 1.06-1.94), diabetes (HR, 1.55; 95%CI, 1.00-2.40), bilateral lesions (HR, 2.73; 95%CI, 1.12-6.65) and posterior cerebral artery involvement (HR, 1.44; 95%CI, 1.08-1.90) were positively associated with follow-up stroke (all P < 0.05). Pediatric onset (HR, 0.46; 95%CI, 0.26-0.82) was inversely and hyperlipidemia (HR, 1.83; 95%CI, 1.23-2.73), smoking (HR, 1.86; 95%CI, 1.13-3.07), high Suzuki angiographic stage (HR, 1.71, 95%CI, 1.09-2.70), poor admission neurologic status (HR, 8.93; 95%CI, 6.49-12.29) and follow-up stroke (HR, 8.31; 95%CI, 6.01-11.49) were positively associated with poor neurologic outcome at the last follow-up visit (all P < 0.05). The factors were not consistent in the different groups of age at onset.

Conclusions: In our study, p.R4810K may play no role in long-term outcomes in Chinese MMD. Clinical features including age at onset, initial symptoms, risk factors of stroke, imaging, poor admission neurologic status were associated with poor outcomes in MMD after EDAS.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105847DOI Listing
July 2021

Porcine circovirus type 2 infection attenuates the K63-linked ubiquitination of STING to inhibit IFN-β induction via p38-MAPK pathway.

Vet Microbiol 2021 Jul 4;258:109098. Epub 2021 May 4.

College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, China. Electronic address:

Porcine circovirus 2 (PCV2) has been proved to increase the risk of other pathogens infection via immunosuppression. Although the co-infection of PCV2 and porcine parvovirus (PPV) is commonly observed in worldwide, the relative immune mechanisms promoting PPV infection in PCV2-infected piglets are currently unknown. Herein, we found that PCV2 infection suppressed IFN-β expression and promoted PPV infection in the piglets. Consistent with this finding, we confirmed that PCV2 infection significantly inhibited the induction of IFN-β to promote PPV replication in cell level. Furthermore, PCV2 infection attenuated the K63-linked ubiquitination of STING induced by PPV, blocked the formation of complex of STING, TBK1 and IRF3, and further prevented the phosphorylation of TBK1 and IRF3, resulting in a decreased IFN-β transcription response to PPV infection. Consistently, using cGAMP to direct stimulate STING also appeared a reduced STING-K63 ubiquitination and IFN-β induction in PCV2-infected cells. However, we noted that knockdown of p38-MAPK signaling could markedly attenuate the inhibitory effect of PCV2 on STING-K63 ubiquitination, and improve the induction of IFN-β in PCV2-infected whenever theses cells were challenged with PPV infection or cGAMP stimulation. Meanwhile, we found that PCV2 infection promoted the phosphorylation of USP21 to inhibit the K63 ubiquitination of STING and the transcription of IFN-β via activation of p38-MAPK signaling. Taken together, our results demonstrate that PCV2 infection activates the p38-MAPK signaling pathway-mediated USP21 phosphorylation to inhibit the K63 ubiquitination of STING, which prevents the phosphorylation and transportation to the nucleus of IRF3, leading to an increase risk for PPV infection.
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http://dx.doi.org/10.1016/j.vetmic.2021.109098DOI Listing
July 2021

Association of intracranial vessel wall enhancement and cerebral hemorrhage in moyamoya disease: a high-resolution magnetic resonance imaging study.

J Neurol 2021 May 6. Epub 2021 May 6.

Department of Radiology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, 100853, China.

Background And Purpose: This study aimed to investigate the enhancement characteristics of vessel wall in patients with moyamoya disease (MMD) using 3D high-resolution magnetic resonance (MR) imaging and their relationship with initial and recurrent intracranial hemorrhage.

Methods: Consecutive patients with MMD were retrospectively analyzed and classified as intracranial hemorrhagic and non-hemorrhagic groups according to the CT or MR images. The clinical features and vessel wall characteristics were compared between the two groups. Logistic regression was performed to relate the vessel wall characteristics to the initial hemorrhage in MMD patients. Patients in hemorrhagic group were followed up after surgery to evaluate the relationship between vessel wall characteristics and recurrent hemorrhage.

Results: A total of 507 MMD patients including 79 hemorrhagic and 428 non-hemorrhagic MMD patients were recruited in the study. We found that hemorrhagic group had more patients with vessel wall enhancements (40.5% vs. 25.7%, p = 0.009) and more eccentric enhanced lesions (17.7% vs. 6.5%, p = 0.001) compared to those in non-hemorrhage group and vessel wall enhancements were independently associated with ipsilateral initial hemorrhage after adjusted for clinical factors (OR = 1.99, CI 1.20-3.28, p = 0.007). Furthermore, three recurrent intracranial hemorrhagic episodes in the present study were all observed in MMD patients with vessel wall enhancement during the long-term follow-up after surgery.

Conclusions: Wall enhancement of intracranial vessels was significantly associated with intracranial hemorrhage in MMD patients. Our findings suggest that vessel wall enhancement may serve as a marker of intracranial hemorrhage.
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http://dx.doi.org/10.1007/s00415-021-10587-6DOI Listing
May 2021

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

Cell Death Dis 2021 05 4;12(5):442. Epub 2021 May 4.

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

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

Aptamers: The Powerful Molecular Tools for Virus Detection.

Chem Asian J 2021 Jun 1;16(11):1298-1306. Epub 2021 May 1.

State Key Laboratory of Medicinal Chemical biology, College of Life Sciences, Nankai University, Tianjin, 300350, P. R. China.

Aptamers are short single-stranded DNA or RNA oligonucleotides selected by the technique of systematic evolution of ligands by exponential enrichment (SELEX). Aptamers have been demonstrated to bind various targets from small-molecule to cells or even tissues in the way of antibodies. Thus, they are called chemical antibodies. We summarize and evaluate recent developments in aptamer-based sensors (for short aptasensors) for virus detection in this review. These aptasensors are mainly classified into optical and electronic aptasensors based on the type of transducer. Nowadays, the smartphone has become the most widely used mobile device with billions of users worldwide. Considering the ongoing COVID-19 outbreak, smartphone-based aptasensors for a portable and point-of-care test (POCT) of COVID-19 detection will be of great importance in the future.
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http://dx.doi.org/10.1002/asia.202100242DOI Listing
June 2021

Prenatal diagnosis of fetal congenital mesoblastic nephroma by ultrasonography combined with MR imaging: A case report and literature review.

Medicine (Baltimore) 2021 Jan;100(3):e24034

Department of Center for Reproductive Medicine and Center for Prenatal Diagnosis, The First Hospital of Jilin University, Changchun, Jilin, P.R. China.

Rationale: Fetal congenital mesoblastic nephroma (CMN) is a rare renal tumor, characterized by polyhydramnios, premature birth, and neonatal hypertension. In the prenatal stage, it is particularly difficult to diagnose CMN either by ultrasonography or magnetic resonance imaging (MRI). Thus, CMN is frequently detected in the third trimester in the clinical scenario.

Patient Concerns: A 29-year-old G2P0 pregnant woman took routine prenatal examinations in our hospital. The fetal right kidney abnormality was not observed after 2 systematical ultrasonic examinations (at 24 and 31 weeks of gestation respectively), and only an increase was noticed in the amniotic fluid index (from 19.3 to 20.8 cm).

Diagnosis: CMN was detected by antenatal ultrasonography and MRI as a fetal right renal mass at 35 weeks of gestation in our hospital.

Interventions: The pregnant woman was admitted at a gestational age of 38 weeks and 5 days due to alterations in renal function. Further, the pregnant woman was administered with "oxytocin" to promote delivery, and the neonate underwent a right nephrectomy on the 9th day after birth.

Outcomes: The pathological examination confirmed a cellular type of right CMN. The neonate recovered well after operation without adjuvant treatment. During 6 months of follow-up, the neonate grew well and showed no signs of recurrence or metastasis.

Conclusion: Polyhydramnios detected during prenatal examination required attention due to the risk of malformation of fetal urinary system. Prenatal ultrasonography combined with MRI could not only clearly identify the origin of the tumor, but also distinguish the correlation between the tumor and adjacent structures, thereby leading to early diagnosis and favorable prognosis.
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http://dx.doi.org/10.1097/MD.0000000000024034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837828PMC
January 2021

Learning Speech Production and Perception through Sensorimotor Interactions.

Cereb Cortex Commun 2021 27;2(1):tgaa091. Epub 2020 Nov 27.

Department of Electrical Engineering, Columbia University, New York, NY 10027, USA.

Action and perception are closely linked in many behaviors necessitating a close coordination between sensory and motor neural processes so as to achieve a well-integrated smoothly evolving task performance. To investigate the detailed nature of these sensorimotor interactions, and their role in learning and executing the skilled motor task of speaking, we analyzed ECoG recordings of responses in the high-γ band (70-150 Hz) in human subjects while they listened to, spoke, or silently articulated speech. We found elaborate spectrotemporally modulated neural activity projecting in both "forward" (motor-to-sensory) and "inverse" directions between the higher-auditory and motor cortical regions engaged during speaking. Furthermore, mathematical simulations demonstrate a key role for the forward projection in "learning" to control the vocal tract, beyond its commonly postulated predictive role during execution. These results therefore offer a broader view of the functional role of the ubiquitous forward projection as an important ingredient in learning, rather than just control, of skilled sensorimotor tasks.
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http://dx.doi.org/10.1093/texcom/tgaa091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811190PMC
November 2020

Validation of choroidal anastomosis on high-resolution magnetic resonance imaging as an imaging biomarker in hemorrhagic moyamoya disease.

Eur Radiol 2021 Jul 14;31(7):4548-4556. Epub 2021 Jan 14.

Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Objectives: This study aimed to investigate the association between dilation and proliferation and anastomosis of perforating arteries, and intracranial hemorrhage in moyamoya disease (MMD) patients, using high-resolution magnetic resonance imaging (HRMRI).

Methods: Adult patients with MMD at advanced stages were prospectively enrolled and underwent HRMRI exams. Dilation and proliferation of the lenticulostriate artery (LSA), medullary artery, and anterior or posterior choroidal arteries (AChA or PChA) were assessed. Abnormal anastomoses were identified between (1) the LSA and the medullary or insular arteries; (2) the thalamo-geniculate, thalamo-tuberal, or thalamo-perforating arteries and the medullary or insular arteries; and (3) the AChA or PChA and the medullary or insular arteries. The association between these variables and hemorrhagic events was calculated using univariate and multivariate analyses.

Results: Fifty patients (14 men; mean age, 35.4 ± 9.7 years) were finally analyzed, including 17 hemorrhagic patients and 33 non-hemorrhagic patients. The inter-rater agreement for the qualitative evaluation of perforating arteries was good. Dilation and proliferation of the AChA or PChA (88.2% versus 54.5%, p = 0.027), and choroidal anastomosis (64.7% versus 18.2%, p = 0.002) were more frequently observed in patients with hemorrhage. Multivariate logistic regression showed that choroidal anastomosis remained significantly associated with hemorrhage (odds ratio = 5.95, 95% confidence interval = 1.21-29.25, p = 0.028).

Conclusions: Choroidal anastomosis is independently associated with hemorrhagic events in adult patients with MMD at advanced stages. HRMRI can provide detailed information on both the anatomies and abnormal collaterals in MMD, which facilitates risk estimates of bleeding in MMD.

Key Points: • High-resolution magnetic resonance imaging allows for the evaluation of perforating arteries in patients with moyamoya disease. • Choroidal anastomosis is associated with hemorrhagic events in patients with moyamoya disease. • High-resolution magnetic resonance imaging might facilitate further grading and classification of moyamoya vessels.
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http://dx.doi.org/10.1007/s00330-020-07479-0DOI Listing
July 2021

Novel variants in CIITA caused type II bare lymphocyte syndrome: A case report.

Asian Pac J Allergy Immunol 2021 Jan 2. Epub 2021 Jan 2.

Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Background: Type II bare lymphocyte syndrome (BLS II) group A is a rare primary severe immunodeficiency caused by defects in CIITA, one of genes encoding transcriptional regulatory factors for MHC II molecules.

Objective: To report a Chinese boy with mutation of CIITA.

Methods: By reviewing the clinical data of the child and performing a literature search of BLS II group A.

Results: The patient was presented with persistent pneumonia, chronic diarrhea, urinary tract infection, rash, failure to thrive and special facial characteristics. The patient carried novel mutations in CIITA (c.1243delC, p.R415fs*2 and c.3226C>T, p.R1076W) which were identified by next-generation sequencing and confirmed by Sanger sequencing.

Conclusions: This study found novel mutations in the CIITA gene of BLS II, which complemented the mutation spectrum and contributed to the diagnosis, treatment, genetic counseling and prenatal diagnosis of BLS II.
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http://dx.doi.org/10.12932/AP-020720-0898DOI Listing
January 2021

Astragalus membranaceus and Salvia miltiorrhiza ameliorates cyclosporin A-induced chronic nephrotoxicity through the "gut-kidney axis".

J Ethnopharmacol 2021 Apr 28;269:113768. Epub 2020 Dec 28.

Shandong University of Traditional Chinese Medicine, Jinan, 250014, China.

Ethnopharmacological Relevance: The combination of Astragalus membranaceus and Salvia miltiorrhiza (AS) is an effective prescription that is widely used to treat chronic kidney disease (CKD) clinically in traditional Chinese medicine. Our previous studies have shown that AS can alleviate early CKD through the "gut-kidney axis", but the regulatory role of AS in the "gut-kidney axis" in the middle and late stages of CKD caused by cyclosporin A-induced chronic nephrotoxicity (CICN) has remained unclear.

Aim Of The Study: To explore the protective effect of AS by regulating the intestinal flora to further control the miRNA-mRNA interaction profiles in CICN.

Materials And Methods: Thirty-two mice were divided into four groups: Normal (N) (olive oil), Model (M) (CsA, 30 mg kg d), AS (CsA + AS, 30 + 8.4 g kg d) and FMT-AS (CsA + Faeces of AS group, 30 mg + 10 mL kg d). The mice were treated for 6 weeks. Changes in renal function related metabolites were detected, pathological changes in the colon and kidney were observed, and 16S rDNA sequencing was performed on mouse faeces. In addition, miRNA and mRNA sequencing were performed on the kidney to construct differential expression (DE) profiles of the other 3 groups compared with group M. The target mRNAs among the DE miRNAs were then predicted, and an integrated analysis was performed with the DE mRNAs to annotate gene function by KEGG. DE miRNAs and DE mRNAs related to CICN in the overlapping top 20 KEGG pathways were screened and verified.

Results: Eight metabolites that could worsen renal function were increased in group M, accompanied by thickening of the glomerular basement membrane, vacuolar degeneration of renal tubules, and proliferation of collagen fibres, while AS and FMT-AS intervention amended these changes to varying degrees. Simultaneously, intestinal permeability increased, the abundance and diversity of the flora decreased, and the ratio of Firmicum to Bacteroides (F/B) increased in group M. The AS and FMT-AS treatments reversed the flora disorder and increased probiotics producing butyric acid and lactic acid, especially Akkermansia and Lactobacillus, which might regulate the 12 overlapping top 20 KEGG pathways, such as Butanoate metabolism, Tryptophan metabolism and several RF-related pathways, leading to the remission of renal metabolism. Finally, 15 DE miRNAs and 45 DE mRNAs were screened as the therapeutic targets, and the results coincided with the sequencing results.

Conclusion: AS could alleviate renal fibrosis and metabolism caused by CICN through the "gut-kidney axis". Probiotics such as Akkermansia and Lactobacillus were the primary driving factors, and the miRNA-mRNA interaction profiles, especially Butanoate metabolism and Tryptophan metabolism, may be an important subsequent response and regulatory mechanism.
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http://dx.doi.org/10.1016/j.jep.2020.113768DOI Listing
April 2021

Eradication of T-ALL Cells by CD7-targeted Universal CAR-T Cells and Initial Test of Ruxolitinib-based CRS Management.

Clin Cancer Res 2021 Mar 24;27(5):1242-1246. Epub 2020 Nov 24.

920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, Kunming, Yunnan, P.R. China.

Purpose: Although chimeric antigen receptor T-cell (CAR-T) therapy development for B-cell malignancies has made significant progress in the last decade, broadening the success to treating T-cell acute lymphoblastic leukemia (T-ALL) has been limited. We conducted two clinical trials to verify the safety and efficacy of GC027, an "off-the-shelf" allogeneic CAR-T product targeting T-cell antigen, CD7. Here, we report 2 patients as case reports with relapsed/refractory T-ALL who were treated with GC027.

Patients And Methods: Both the trials reported here were open-label and single-arm. A single infusion of GC027 was given to each patient after preconditioning therapy.

Result: Robust expansion of CAR-T cells along with rapid eradication of CD7 T lymphoblasts were observed in the peripheral blood, bone marrow, and cerebrospinal fluid. Both patients achieved complete remission with no detectable minimal residual disease. At data cutoff, 30 September 2020, 1 of the 2 patients remains in ongoing remission for over 1 year after CAR T-cell infusion. Grade 3 cytokine release syndrome (CRS) occurred in both patients and was managed by a novel approach with a ruxolitinib-based CRS management. Ruxolitinib showed promising activity in a preclinical study conducted at our center. No graft-versus-host disease was observed.

Conclusions: The two case reports demonstrate that a standalone therapy with this novel CD7-targeted "off-the-shelf" allogeneic CAR-T therapy may provide deep and durable responses in select patients with relapsed/refractory T-ALL. GC027 might have a potential to be a promising new approach for treating refractory/relapsed T-ALL. Further studies are warranted.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-1271DOI Listing
March 2021

Hamartin: An Endogenous Neuroprotective Molecule Induced by Hypoxic Preconditioning.

Front Genet 2020 30;11:582368. Epub 2020 Sep 30.

Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.

Hypoxic/ischemic preconditioning (HPC/IPC) is an innate neuroprotective mechanism in which a number of endogenous molecules are known to be involved. Tuberous sclerosis complex 1 (TSC1), also known as hamartin, is thought to be one such molecule. It is also known that hamartin is involved as a target in the rapamycin (mTOR) signaling pathway, which functions to integrate a variety of environmental triggers in order to exert control over cellular metabolism and homeostasis. Understanding the role of hamartin in ischemic/hypoxic neuroprotection will provide a novel target for the treatment of hypoxic-ischemic disease. Therefore, the proposed molecular mechanisms of this neuroprotective role and its preconditions are reviewed in this paper, with emphases on the mTOR pathway and the relationship between the expression of hamartin and DNA methylation.
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http://dx.doi.org/10.3389/fgene.2020.582368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556298PMC
September 2020

Genome-Wide Identification of Long Non-coding RNAs in the Gravid Ectoparasite .

Front Genet 2020 16;11:575680. Epub 2020 Oct 16.

Apicultural Research Institute, College of Animal Science and Technology, Yangzhou University, Yangzhou, China.

Long non-coding RNAs (lncRNAs) emerge as critical regulators across a wide variety of biological functions in living organisms. However, to date, no systematic characterization of lncRNAs has been investigated in the ectoparasitic mite , the most severe biotic threat to honey bees worldwide. Here, we performed an initial genome-wide identification of lncRNAs in via high-throughput sequencing technology and reported, for the first time, the transcriptomic landscape of lncRNAs in the devastating parasite. By means of a lncRNA identification pipeline, 6,645 novel lncRNA transcripts, encoded by 3,897 gene loci, were identified, including 2,066 sense lncRNAs, 2,772 lincRNAs, and 1,807 lncNATs. Compared with protein-coding mRNAs, lncRNAs are shorter in terms of full length, as well as of the ORF length, contain less exons, and express at lower level. GO term and KEGG pathway enrichment analyses of the lncRNA target genes demonstrated that these predicted lncRNAs may be potentially responsible for the regulatory functions of cellular and biological progresses in the reproductive phase of . To our knowledge, this is the first catalog of lncRNA profile in the parasitiformes species, providing a valuable resource for genetic and genomic studies. Understanding the characteristics and features of lncRNAs in would promote sustainable parasite control.
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http://dx.doi.org/10.3389/fgene.2020.575680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596327PMC
October 2020

LRRC31 inhibits DNA repair and sensitizes breast cancer brain metastasis to radiation therapy.

Nat Cell Biol 2020 10 1;22(10):1276-1285. Epub 2020 Oct 1.

Department of Neurosurgery, Yale University, New Haven, CT, USA.

Breast cancer brain metastasis (BCBM) is a devastating disease. Radiation therapy remains the mainstay for treatment of this disease. Unfortunately, its efficacy is limited by the dose that can be safely applied. One promising approach to overcoming this limitation is to sensitize BCBMs to radiation by inhibiting their ability to repair DNA damage. Here, we report a DNA repair suppressor, leucine-rich repeat-containing protein 31 (LRRC31), that was identified through a genome-wide CRISPR screen. We found that overexpression of LRRC31 suppresses DNA repair and sensitizes BCBMs to radiation. Mechanistically, LRRC31 interacts with Ku70/Ku80 and the ataxia telangiectasia mutated and RAD3-related (ATR) at the protein level, resulting in inhibition of DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) recruitment and activation, and disruption of the MutS homologue 2 (MSH2)-ATR module. We demonstrate that targeted delivery of the LRRC31 gene via nanoparticles improves the survival of tumour-bearing mice after irradiation. Collectively, our study suggests LRRC31 as a major DNA repair suppressor that can be targeted for cancer radiosensitizing therapy.
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http://dx.doi.org/10.1038/s41556-020-00586-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962994PMC
October 2020

Remote Ischemic Conditioning Improves Attention Network Function and Blood Oxygen Levels in Unacclimatized Adults Exposed to High Altitude.

Aging Dis 2020 Jul 23;11(4):820-827. Epub 2020 Jul 23.

1Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.

Remote ischemic conditioning (RIC) confers protection on major organs from hypoxic/ischemic injuries; however, its impacts on attention network function and blood oxygen levels in unacclimatized adults exposed to high altitudes have yet to be elucidated. In this study, we recruited 120 healthy male volunteers, of which one was exposed to high altitude and the other was exposed to low altitude. The two cohorts were further divided into RIC and sham control groups. The attentional network test (ANT) was performed to evaluate cognitive function before and after RIC treatment. Other outcomes such as heart rate, blood pressure, blood oxygen saturation, cerebral tissue oxygenation index (CTOI), and cerebrovascular hemodynamic indices were also evaluated. Prior to RIC treatment, there were no significant differences in orienting or executive function between the treatment and control arms of either cohort. Alerting function was significantly lower in the high-altitude cohort than in the low-altitude cohort. There were significant reductions in both blood oxygen and CTOI in the high-altitude cohort relative to the low-altitude cohort, while the pulse index (PI) of the former cohort was significantly increased. After RIC treatment, there was a significant difference in alerting function between the high-altitude RIC group and its associated control. The CTOI of the treatment group increased from 60.39±3.40% to 62.78±4.40%, and blood oxygenation also improved. Furthermore, this group showed a significant reduction in its PI. Exposure to high-altitude environments had a significant impact on alerting function, blood oxygen, CTOI, and PI. RIC ameliorated changes in attentional function, as well as blood oxygen and CTOI, suggesting that it potentially alters cerebrovascular compliance upon exposure to high altitude.
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http://dx.doi.org/10.14336/AD.2019.0605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390527PMC
July 2020

HOXD3 was negatively regulated by YY1 recruiting HDAC1 to suppress progression of hepatocellular carcinoma cells via ITGA2 pathway.

Cell Prolif 2020 Aug 17;53(8):e12835. Epub 2020 Jun 17.

Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.

Objectives: HOXD3 is associated with progression of multiple types of cancer. This study aimed to identify the association of YY1 with HOXD3-ITGA2 axis in the progression of hepatocellular carcinoma.

Materials And Methods: Bioinformatics assay was used to identify the effect of YY1, HOXD3 and ITGA2 expression in HCC tissues. The function of YY1 and HOXD3 in HCCs was determined by qRT-PCR, MTT, apoptosis, Western blotting, colony formation, immunohistochemistry, and wound-healing and transwell invasion assays. The relationship between YY1 and HOXD3 or HOXD3 and ITGA2 was explored by RNA-Seq, ChIP-PCR, dual luciferase reports and Pearson's assays. The interactions between YY1 and HDAC1 were determined by immunofluorescence microscopy and Co-IP.

Results: Herein, we showed that the expression of YY1, HOXD3 and ITGA2 associated with the histologic and pathologic stages of HCC. Moreover, YY1, recruiting HDAC1, can directly target HOXD3 to regulate progression of HCCs. The relationship between YY1 and HOXD3 was unknown until uncovered by our present investigation. Furthermore, HOXD3 bound to promoter region of ITGA2 and up-regulated the expression, thus activating the ERK1/2 signalling and inducing HCCs proliferation, metastasis and migration in the vitro and vivo.

Conclusions: Therefore, HOXD3, a target of YY1, facilitates HCC progression via activation of the ERK1/2 signalling by promoting ITGA2. This finding provides a new whole way to HCC therapy by serving YY1-HOXD3-ITGA2 regulatory axis as a potential therapeutic target for HCC therapy.
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http://dx.doi.org/10.1111/cpr.12835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445403PMC
August 2020

The research on propagation characteristics of acoustic emission signals in stiffened plates based on the multipath propagation model.

Ultrasonics 2020 Dec 22;108:106177. Epub 2020 May 22.

College of Mechanical and Electrical Engineering, Beijing University of Chemical Technology, Beijing 100029, China.

Mechanical equipment with the stiffener has a strong interference with the propagation of acoustic emission (AE) signals from faults, reducing the accuracy of fault detection. This paper conducts an in-depth study of the interaction between AE signals and the stiffener. The installation constraints, that can separate the direct signal, signals scattered from the stiffener and signals reflected from the boundary in the time domain, for sensors are deduced based on the multipath propagation model of AE signals in the stiffened plate. On this basis, the scattering characteristics of AE signals with different frequencies in different height stiffened plates are predicted by simulations. Moreover, the reflection and transmission coefficients are calculated to quantify the scattering characteristics. The results show that the signal, undergoing a "T-shaped" transformation at the stiffener, generates various modes, among which the transmission signal accounted for the largest proportion. In addition, experiments are performed to verify the numerical simulations, and the results are in good agreement with the numerical simulations. This work clarifies the propagation characteristics of AE signals in stiffened plates, and the research can optimize the spatial arrangement for sensors.
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http://dx.doi.org/10.1016/j.ultras.2020.106177DOI Listing
December 2020

Porcine DNAJB6 promotes PCV2 replication via enhancing the formation of autophagy in host cells.

Vet Res 2020 May 7;51(1):61. Epub 2020 May 7.

College of Veterinary Medicine, Northwest A&F University, Yangling, China.

Hsp40/DnaJ family proteins play important roles in the infection process of various viruses. Porcine DNAJB6 (pDNAJB6) is a major member of this family, but its role in modulating the replication of porcine circovirus type 2 (PCV2) is still unclear. In the present study, pDNAJB6 was found to be significantly upregulated by PCV2 infection, and confirmed to be interacted with PCV2 capsid (Cap) protein and co-localized at both cytoplasm and nucleus in the PCV2-infected cells. Knockout of pDNAJB6 significantly reduced the formation of autophagosomes in PCV2-infected cells or in the cells expressing Cap protein, whereas overexpression of pDNAJB6 showed an opposite effect. In addition, the domain mapping assay showed that the J domain of pDNAJB6 (amino acids (aa) 1-99) and the C terminus of Cap (162-234 aa) were required for the interaction of pDNAJB6 with Cap. Notably, the interaction of pDNAJB6 with Cap was very important to promoting the formation of autophagosomes induced by PCV2 infection or Cap expression and enhancing the replication of PCV2. Taken together, the results presented here show a novel function of pDNAJB6 in regulation of porcine circovirus replication that pDNAJB6 enhances the formation of autophagy to promote viral replication through interacting with viral capsid protein during PCV2 infection.
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http://dx.doi.org/10.1186/s13567-020-00783-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203849PMC
May 2020

MicroRNA and mRNA analysis of angiotensin II-induced renal artery endothelial cell dysfunction.

Exp Ther Med 2020 Jun 19;19(6):3723-3737. Epub 2020 Mar 19.

Department of Clinical Chinese Medicine integrated with Western Medicine, First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P.R. China.

Continuous activation of angiotensin II (Ang II) induces renal vascular endothelial dysfunction, inflammation and oxidative stress, all of which may contribute to renal damage. MicroRNAs (miRs/miRNAs) play a crucial regulatory role in the pathogenesis of hypertensive nephropathy (HN). The present study aimed to assess the differential expression profiles of potential candidate genes involved in Ang II-induced rat renal artery endothelial cell (RRAEC) dysfunction and explore their possible functions. In the present study, the changes in energy metabolism and autophagy function in RRAECs were evaluated using the Seahorse XF Glycolysis Stress Test and dansylcadaverine/transmission electron microscopy following exposure to Ang II. Subsequently, mRNA-miRNA sequencing experiments were performed to determine the differential expression profiles of mRNAs and miRNAs. Integrated bioinformatics analysis was applied to further explore the molecular mechanisms of Ang II on endothelial injury induced by Ang II. The present data supported the notion that Ang II upregulated glycolysis levels and promoted autophagy activation in RRAECs. The sequencing data demonstrated that 443 mRNAs and 58 miRNAs were differentially expressed (DE) in response to Ang II exposure, where 66 mRNAs and 55 miRNAs were upregulated, while 377 mRNAs and 3 miRNAs were downregulated (fold change >1.5 or <0.67; P<0.05). Functional analysis indicated that DE mRNA and DE miRNA target genes were mainly associated with cell metabolism (metabolic pathways), differentiation (Th1 and Th2 cell differentiation), autophagy (autophagy-animal and autophagy-other) and repair (RNA-repair). To the best of the authors' knowledge, this is the first report on mRNA-miRNA integrated profiles of Ang II-induced RRAECs. The present results provided evidence suggesting that the miRNA-mediated effect on the 'mTOR signaling pathway' might play a role in Ang II-induced RRAEC injury by driving glycolysis and autophagy activation. Targeting miRNAs and their associated pathways may provide valuable insight into the clinical management of HN and may improve patient outcome.
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http://dx.doi.org/10.3892/etm.2020.8613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185074PMC
June 2020

Predictive role of heterozygous p.R4810K of in the phenotype of Chinese moyamoya disease.

Neurology 2020 02 16;94(7):e678-e686. Epub 2020 Jan 16.

From the Department of Nutrition and Food Hygiene, School of Public Health (Y.W., Q.Z., L.Y., M.S., M.M., Q.L., K.Z., S.L., M.L., F.Z., F.N., W.L.), China Medical University, Shenyang; Department of Neurosurgery (Z. Zhang, Z. Zou, D.L., C.H., X.B., F.H., H.W., L.D.), the Fifth Medical Centre, Chinese PLA General Hospital (Former 307th Hospital of the PLA), Beijing; and Department of Neurology (L.W., K.W.), the First Affiliated Hospital of Anhui Medical University, Hefei, China.

Objective: Precise genetic analyses were conducted with ring finger protein 213 () in relation to a particular clinical phenotype in Chinese patients with moyamoya disease (MMD) to determine whether heterozygosity is responsible for the early-onset and severe form of this disease.

Methods: A case-control study for p.R4810K involving 1,385 Chinese patients with MMD and 2,903 normal control participants was performed. Correlation analyses between genotype and phenotype or different clinical features were also statistically explored.

Results: An obvious trend was observed: the carrying rate of p.R4810K gradually decreased when moving from coastal cities in northeast, north, and east China to southern cities or inland areas. Higher frequencies of p.R4810K were observed in patients with MMD compared with control participants (odds ratio, 48.1; 95% confidence interval, 29.1-79.6; = 1.6 × 10). In addition, the onset age of all patients with the GA and AA genotypes were lower than with the GG genotype, and the median onset age was 40.0, 36.0, and 11.5 years with GG, GA, and AA, respectively, thereby confirming that those with GA or AA could acquire MMD during early life stages. Patients with MMD with the GA genotype were more susceptible to posterior cerebral artery (PCA) involvement compared to those with the GG genotype (38.4% vs 23.3%, = 8.3 × 10).

Conclusions: Strong evidence suggests that the carrying rate of p.R4810K is closely related MMD risk in China and has given rise to an earlier onset age and more severe PCA involvement.
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http://dx.doi.org/10.1212/WNL.0000000000008901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176299PMC
February 2020

MicroRNA-200c-3p inhibits proliferation and migration of renal artery endothelial cells by directly targeting ZEB2.

Exp Cell Res 2020 02 25;387(2):111778. Epub 2019 Dec 25.

Nephropathy Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250014, China.

Continuous activation of angiotensin II (Ang II) induces renal vascular endothelial dysfunction, inflammation, and oxidative stress, all of which may contribute to renal damage. It is well established that microRNAs (miRNAs) play crucial regulatory roles in the pathogenesis of hypertensive renal damage. However, the detailed mechanisms and regulatory roles of miRNAs as therapeutic targets underlying Ang II-induced renal artery endothelial cell dysfunction in hypertensive renal damage have yet to be fully elucidated. The present study aimed to explore the expression status and putative role of miRNA-200c-3p in mediating the progression of hypertensive renal damage. We carried out real-time quantitative PCR (RT-qPCR) to detect the expression of miRNA-200c-3p in rat renal artery endothelial cells (RRAECs) induced by Ang II. MTT and transwell assays were utilized to evaluate the effects of miRNA-200c-3p on cell proliferation and migration, respectively. The present results revealed that the expression of miRNA-200c-3p was significantly upregulated in RRAECs exposed to Ang II compared with that of normal cells. miRNA-200c-3p overexpression markedly inhibited cell proliferation and migration of Ang II-induced RRAECs. Furthermore, bioinformatics predictions and dual-luciferase reporter assays indicated that zinc finger E-box-binding homeobox 2 (ZEB2) was a direct target gene of miRNA-200c-3p and that ZEB2 expression was inversely correlated with the levels of miRNA-200c-3p in RRAECs after exposure to Ang II. The effects of ZEB2 silencing were similar to the inhibitory effects observed following miRNA-200c-3p overexpression, and recovered ZEB2 expression reversed the anti-proliferative and anti-migratory influence of miRNA-200c-3p upregulation in RRAECs induced by Ang II. The present study indicated that miRNA-200c-3p might suppress the proliferation and migration of Ang II-induced RRAECs by targeting ZEB2. The miRNA-200c-3p/ZEB2 axis will provide valuable insights into the clinical management of hypertension-related kidney disease.
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http://dx.doi.org/10.1016/j.yexcr.2019.111778DOI Listing
February 2020

Clinical characteristics and leptomeningeal collateral status in pediatric and adult patients with ischemic moyamoya disease.

CNS Neurosci Ther 2020 01 13;26(1):14-20. Epub 2019 Apr 13.

Department of Neurosurgery, The Fifth Medical Center of Chinese PLA General Hospital, The 307th Hospital of the Chinese People's Liberation Army, Academy of Military Medical Science, Beijing, China.

Aim: Previous studies have found significant differences in clinical characteristics between pediatric and adult moyamoya disease (MMD) patients, but few studies have focused on the factors underlying these differences. We aimed to investigate the differences in leptomeningeal collateral (LMC) status between pediatric and adult MMD patients and to analyze the effects of LMCs on clinical characteristics and therapeutic prognosis.

Methods: We retrospectively analyzed 214 MMD patients from January 2014 to January 2016. Clinical characteristics and LMC status were compared between the pediatric and adult patients. LMC status was graded as good or poor depending on the retrograde flow from the posterior cerebral artery (PCA) on digital subtraction angiography (DSA).

Results: A total of 83 pediatric and 131 adult (1:1.6) MMD patients were analyzed. Pediatric patients were more likely to experience a transient ischemic attack (81%), whereas adult patients were more likely to experience infarction (51%). Regarding the different MMD stages (the early, medium, and advanced stages corresponded to Suzuki stages 1-2, 3-4, and 5-6, respectively), the prevalence of good LMC status was higher for pediatric patients than for adult patients in the early stage (P = 0.047) and the medium stage (P = 0.001), but there were no differences between these patient groups in the advanced stage (P = 0.547). Worse postoperative angiographic outcomes (P = 0.017) were found in adult patients than in pediatric patients in the medium stage. Poor LMC status had strong correlations with infarction (P < 0.001 and P = 0.017) and poor postoperative outcomes (P = 0.003 and P = 0.043) in both pediatric and adult patients.

Conclusions: Pediatric MMD patients have greater patency and a greater ability to establish good LMC status than adult patients, and poor LMC status has a strong correlation with severe clinical symptoms and poor postoperative outcomes. LMC status may be an important factor in the differences in clinical characteristics and prognosis between pediatric and adult MMD patients.
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http://dx.doi.org/10.1111/cns.13130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930821PMC
January 2020

Porcine Circovirus Type 2 Rep Enhances IL-10 Production in Macrophages via Activation of p38-MAPK Pathway.

Viruses 2019 12 10;11(12). Epub 2019 Dec 10.

College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.

Porcine circovirus type 2 (PCV2) is one of the major threats to pig farms worldwide. Although PCV2 has been identified to promote IL-10 production, the detailed regulatory roles of PCV2 Rep for IL-10 production remain unclear. Herein, we first found that PCV2 Rep, rather than PCV1 Rep, enhanced IL-10 expression at the later phase of PCV2 infection in porcine alveolar macrophages (PAMs). Furthermore, we found that PCV2 Rep directly activated the p38-MAPK pathway to promote transcription factors NF-κB p50 and Sp1 binding to the promoter, but PCV1 Rep did not. During PCV2 infection, however, PCV2 Rep promoted the binding activities of NF-κB p50 and Sp1 with the promoter only at the later phase of PCV2 infection, since Rep proteins only expressed at the later phase of the infection. Moreover, silence of the thymine DNA glycosylase (TDG), a Rep-binding protein, significantly reduced the binding activities of NF-κB p50 and Sp1 with promoter, resulting in the reduction of IL-10 production in PCV2-inoculated PAMs at the later phase of infection. Taken together, our results demonstrate that Rep proteins enhance IL-10 production during PCV2 infection of PAMs via activation of p38-MAPK pathways, in which host TDG is a critical mediator.
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http://dx.doi.org/10.3390/v11121141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950681PMC
December 2019

On the Validation of a Multiple-Network Poroelastic Model Using Arterial Spin Labeling MRI Data.

Front Comput Neurosci 2019 3;13:60. Epub 2019 Sep 3.

Department of Mechanical Engineering, University College London, London, United Kingdom.

The Multiple-Network Poroelastic Theory (MPET) is a numerical model to characterize the transport of multiple fluid networks in the brain, which overcomes the problem of conducting separate analyses on individual fluid compartments and losing the interactions between tissue and fluids, in addition to the interaction between the different fluids themselves. In this paper, the blood perfusion results from MPET modeling are partially validated using cerebral blood flow (CBF) data obtained from arterial spin labeling (ASL) magnetic resonance imaging (MRI), which uses arterial blood water as an endogenous tracer to measure CBF. Two subjects-one healthy control and one patient with unilateral middle cerebral artery (MCA) stenosis are included in the validation test. The comparison shows several similarities between CBF data from ASL and blood perfusion results from MPET modeling, such as higher blood perfusion in the gray matter than in the white matter, higher perfusion in the periventricular region for both the healthy control and the patient, and asymmetric distribution of blood perfusion for the patient. Although the partial validation is mainly conducted in a qualitative way, it is one important step toward the full validation of the MPET model, which has the potential to be used as a testing bed for hypotheses and new theories in neuroscience research.
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http://dx.doi.org/10.3389/fncom.2019.00060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733888PMC
September 2019
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