Publications by authors named "Yuanchao Zhang"

94 Publications

Tunable Photoluminescence Properties of Microcrystalline Cellulose with Gradually Changing Crystallinity and Crystal Form.

Macromol Rapid Commun 2021 Sep 6;42(17):e2100321. Epub 2021 Aug 6.

Engineering Research Center for Eco-Dyeing and Finishing of Textiles, Key Laboratory of Advanced Textile Materials and Manufacturing Technology, Ministry of Education, College of Textile Science and Engineering (International Institute of Silk), Zhejiang Sci-Tech University, 928 Second Avenue, Hangzhou, Zhejiang, 310018, China.

Nonconventional luminogens with persistent room temperature phosphoresce (p-RTP) are attracting increasing attention owing to their momentous significance and diverse technical applications in optoelectronic and biomedical. So far, the p-RTP emission of some amorphous powders or single crystals has been studied in depth. The p-RTP emission of amorphous and fully crystalline states and their emission properties are widely divergent, while the difference of their p-RTP emission mechanism is still controversial. The relevance between crystallinity change and p-RTP properties is rarely studied. Furthermore, there is almost no research on the photoluminescence (PL) property change and emission mechanism under the crystal form transformation of semi-crystalline polymer. Herein, microcrystalline cellulose (MCC) is chosen as a model compound to explore its crystallinity and the change in luminescence during the crystal form transformation to make up for this gap. By precisely adjusting the crystallinity and crystal cellulose conversion of MCC, the changing trend of quantum efficiency, and p-RTP lifetime is consistent with the change of crystallinity, and the cellulose I may be more beneficial to PL emission than cellulose II. Clustering-triggered emission mechanism can reasonably explain these interesting photophysical processes, which also can be supported by single-crystal analysis and theoretical calculations.
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http://dx.doi.org/10.1002/marc.202100321DOI Listing
September 2021

Connectional asymmetry of the inferior parietal lobule shapes hemispheric specialization in humans, chimpanzees, and rhesus macaques.

Elife 2021 07 2;10. Epub 2021 Jul 2.

Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.

The inferior parietal lobule (IPL) is one of the most expanded cortical regions in humans relative to other primates. It is also among the most structurally and functionally asymmetric regions in the human cerebral cortex. Whether the structural and connectional asymmetries of IPL subdivisions differ across primate species and how this relates to functional asymmetries remain unclear. We identified IPL subregions that exhibited positive allometric in both hemispheres, scaling across rhesus macaque monkeys, chimpanzees, and humans. The patterns of IPL subregions asymmetry were similar in chimpanzees and humans, but no IPL asymmetries were evident in macaques. Among the comparative sample of primates, humans showed the most widespread asymmetric connections in the frontal, parietal, and temporal cortices, constituting leftward asymmetric networks that may provide an anatomical basis for language and tool use. Unique human asymmetric connectivity between the IPL and primary motor cortex might be related to handedness. These findings suggest that structural and connectional asymmetries may underlie hemispheric specialization of the human brain.
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http://dx.doi.org/10.7554/eLife.67600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257252PMC
July 2021

Promoter-sequence determinants and structural basis of primer-dependent transcription initiation in .

Proc Natl Acad Sci U S A 2021 Jul;118(27)

Department of Genetics, Rutgers University, Piscataway, NJ 08854;

Chemical modifications of RNA 5'-ends enable "epitranscriptomic" regulation, influencing multiple aspects of RNA fate. In transcription initiation, a large inventory of substrates compete with nucleoside triphosphates for use as initiating entities, providing an ab initio mechanism for altering the RNA 5'-end. In cells, RNAs with a 5'-end hydroxyl are generated by use of dinucleotide RNAs as primers for transcription initiation, "primer-dependent initiation." Here, we use massively systematic transcript end readout (MASTER) to detect and quantify RNA 5'-ends generated by primer-dependent initiation for ∼4 (∼1,000,000) promoter sequences in The results show primer-dependent initiation in involves any of the 16 possible dinucleotide primers and depends on promoter sequences in, upstream, and downstream of the primer binding site. The results yield a consensus sequence for primer-dependent initiation, YNNW, where TSS is the transcription start site, NN is the primer binding site, Y is pyrimidine, and W is A or T. Biochemical and structure-determination studies show that the base pair (nontemplate-strand base:template-strand base) immediately upstream of the primer binding site (Y:R, where R is purine) exerts its effect through the base on the DNA template strand (R) through interchain base stacking with the RNA primer. Results from analysis of a large set of natural, chromosomally encoded promoters support the conclusions from MASTER. Our findings provide a mechanistic and structural description of how TSS-region sequence hard-codes not only the TSS position but also the potential for epitranscriptomic regulation through primer-dependent transcription initiation.
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http://dx.doi.org/10.1073/pnas.2106388118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271711PMC
July 2021

A joint deep learning model enables simultaneous batch effect correction, denoising, and clustering in single-cell transcriptomics.

Genome Res 2021 Oct 25;31(10):1753-1766. Epub 2021 May 25.

Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Recent developments of single-cell RNA-seq (scRNA-seq) technologies have led to enormous biological discoveries. As the scale of scRNA-seq studies increases, a major challenge in analysis is batch effects, which are inevitable in studies involving human tissues. Most existing methods remove batch effects in a low-dimensional embedding space. Although useful for clustering, batch effects are still present in the gene expression space, leaving downstream gene-level analysis susceptible to batch effects. Recent studies have shown that batch effect correction in the gene expression space is much harder than in the embedding space. Methods such as Seurat 3.0 rely on the mutual nearest neighbor (MNN) approach to remove batch effects in gene expression, but MNN can only analyze two batches at a time, and it becomes computationally infeasible when the number of batches is large. Here, we present CarDEC, a joint deep learning model that simultaneously clusters and denoises scRNA-seq data while correcting batch effects both in the embedding and the gene expression space. Comprehensive evaluations spanning different species and tissues showed that CarDEC outperforms Scanorama, DCA + Combat, scVI, and MNN. With CarDEC denoising, non-highly variable genes offer as much signal for clustering as the highly variable genes (HVGs), suggesting that CarDEC substantially boosted information content in scRNA-seq. We also showed that trajectory analysis using CarDEC's denoised and batch-corrected expression as input revealed marker genes and transcription factors that are otherwise obscured in the presence of batch effects. CarDEC is computationally fast, making it a desirable tool for large-scale scRNA-seq studies.
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http://dx.doi.org/10.1101/gr.271874.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494213PMC
October 2021

Association of Gyrification Pattern, White Matter Changes, and Phenotypic Profile in Patients With Parkinson Disease.

Neurology 2021 05 25;96(19):e2387-e2394. Epub 2021 Mar 25.

From the Key Laboratory for NeuroInformation of Ministry of Education (X.T., Y.Z.), School of Life Science and Technology, University of Electronic Science and Technology of China; and Department of Radiology (D.L., Y.H., L.J., J.Z.), Chongqing University Cancer Hospital, Chongqing Cancer Institute, and Chongqing Cancer Hospital, China.

Objective: To investigate the cortical gyrification changes as well as their relationships with white matter (WM) microstructural abnormalities in the akinetic-rigid (AR) and tremor-dominant (TD) subtypes of Parkinson disease (PD).

Methods: Sixty-four patients with the AR subtype, 26 patients with the TD subtype, and 56 healthy controls (HCs) were included in this study. High-resolution T1-weighted and diffusion-weighted images were acquired for each participant. We computed local gyrification index (LGI) and fractional anisotropy (FA) to identify the cortical gyrification and WM microstructural changes in the AR and TD subtypes.

Results: Compared with HCs, patients with the AR subtype showed decreased LGI in the precentral, postcentral, inferior and superior parietal, middle and superior frontal/temporal, anterior and posterior cingulate, orbitofrontal, supramarginal, precuneus, and some visual cortices, and decreased FA in the corticospinal tract, inferior and superior longitudinal fasciculus, inferior fronto-occipital fasciculus, forceps minor/major, and anterior thalamic radiation. Decreases in LGI and FA of the AR subtype were found to be tightly coupled. LGIs of the left inferior and middle frontal gyrus correlated with Mini-Mental State Examination and Hoehn & Yahr scores of patients with the AR subtype. Patients with the TD subtype showed no significant change in the LGI and FA compared with patients with the AR subtype and HCs.

Conclusions: Our results suggest that cortical gyrification changes in PD are motor phenotype-specific and are possibly mediated by the microstructural abnormalities of the underlying WM tracts.
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http://dx.doi.org/10.1212/WNL.0000000000011894DOI Listing
May 2021

New Trajectory of Clinical and Biomarker Changes in Sporadic Alzheimer's Disease.

Cereb Cortex 2021 06;31(7):3363-3373

Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.

Identifying dynamic changes in biomarkers and clinical profiles is essential for understanding the progression of Alzheimer's disease (AD). The relevant studies have primarily relied on patients with autosomal dominant AD; however, relevant studies in sporadic AD are poorly understood. Here, we analyzed longitudinal data from 665 participants (mean follow-up 4.90 ± 2.83 years). By aligning normal cognition (CN) baseline with a clinical diagnosis of mild cognitive impairment (MCI) or AD, we studied the progression of AD using a linear mixed model to estimate the clinical and biomarker changes from stable CN to MCI to AD. The results showed that the trajectory of hippocampal volume and fluorodeoxyglucose (FDG) was consistent with the clinical measures in that they did not follow a hypothetical sigmoid curve but rather showed a slow change in the initial stage and accelerated changes in the later stage from MCI conversion to AD. Dramatic hippocampal atrophy and the ADAS13 increase were, respectively, 2.5 and 1 years earlier than the MCI onset. Besides, cognitively normal people with elevated and normal amyloid showed no significant differences in clinical measures, hippocampal volume, or FDG. These results reveal that pre-MCI to pre-AD may be a better time window for future clinical trial design.
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http://dx.doi.org/10.1093/cercor/bhab017DOI Listing
June 2021

Structural and functional underpinnings of precentral abnormalities in amyotrophic lateral sclerosis.

Eur J Neurol 2021 05 1;28(5):1528-1536. Epub 2021 Feb 1.

Department of Radiology, Chongqing University Cancer Hospital, Chongqing Cancer Institute, and Chongqing Cancer Hospital, Chongqing, China.

Background And Purpose: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the loss of both upper and lower motor neurons. Studies using various magnetic resonance imaging (MRI) analytical approaches have consistently identified significant precentral abnormalities in ALS, whereas their structural and functional underpinnings remain poorly understood.

Methods: Using cortical thickness, fractional anisotropy (FA), and effective connectivity, we performed a multimodal MRI study to examine the structural and functional alterations associated with precentral abnormalities in patients with ALS (n = 60) compared with healthy controls (n = 60).

Results: Cortical thickness analysis revealed significant cortical thinning in the right precentral gyrus (PCG), superior frontal gyrus, and superior temporal gyrus in patients with ALS. Tractwise white matter microstructure analyses revealed decreased FA in the tracts connected to the PCG cluster in patients with ALS involving the right corticospinal tract and the middle posterior body of the corpus callosum. Additionally, the cortical thickness of the PCG cluster was found to be positively correlated with FA of the tracts connected to the PCG cluster, suggesting that these two structural features are tightly coupled. Using spectral dynamic causal modelling, effective connectivity analysis among the three regions with cortical thinning revealed decreased self-inhibitory influence in the PCG cluster in patients with ALS, which might be an endophenotypic manifestation of an imbalance in inhibitory and excitatory neurotransmitters in this region.

Conclusions: The present data shed new light on the structural and functional underpinnings of precentral abnormalities in ALS.
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http://dx.doi.org/10.1111/ene.14717DOI Listing
May 2021

Fiber-specific white matter reductions in amyotrophic lateral sclerosis.

Neuroimage Clin 2020 2;28:102516. Epub 2020 Dec 2.

Department of Radiology, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing 400030, PR China. Electronic address:

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the loss of both upper and lower motor neurons. Studies using metrics derived from the diffusion tensor model have documented decreased fractional anisotropy (FA) and increased mean diffusivity in the corticospinal tract (CST) and the corpus callosum (CC) in ALS. These studies, however, only focused on microstructural white matter (WM) changes, while the macrostructural alterations of WM tracts in ALS remain unknown. Moreover, studies conducted based on the diffusion tensor model cannot provide information related to specific fiber bundles and fail to clarify which biological characteristics are changing. Using a novel fixel-based analytical method that can characterize the fiber density (FD) and the fiber-bundle cross-section (FC), this study investigated both microstructural and macrostructural changes in the WM in a large cohort of patients with ALS (N = 60) compared with demographically matched healthy controls (N = 60). Compared with healthy controls, we found decreased FD, FC and fiber density and cross-section (FDC, a combined measure of the FD and FC) values in the bilateral CST and the middle posterior body of the CC in patients with ALS, suggesting not only microstructural but also macrostructural abnormalities in these fiber bundles. Additionally, we found that the mean FD and FDC values in the bilateral CST were positively correlated with the revised ALS Functional Rating Scale, indicating that these two indices may serve as potential markers for assessing the clinical severity of ALS. Thus, these findings provide initial evidence for the existence of microstructural and macrostructural abnormalities of the fiber bundles in ALS.
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http://dx.doi.org/10.1016/j.nicl.2020.102516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724379PMC
June 2021

Aberrant Brain Network Integration and Segregation in Diabetic Peripheral Neuropathy Revealed by Structural Connectomics.

Front Neurosci 2020 4;14:585588. Epub 2020 Dec 4.

Department of Radiology, Xiangya Hospital, Central South University, Changsha, China.

Diabetic peripheral neuropathy (DPN) is one of the most common forms of peripheral neuropathy, and its incidence has been increasing. Mounting evidence has shown that patients with DPN have been associated with widespread alterations in the structure, function and connectivity of the brain, suggesting possible alterations in large-scale brain networks. Using structural covariance networks as well as advanced graph-theory-based computational approaches, we investigated the topological abnormalities of large-scale brain networks for a relatively large sample of patients with DPN ( = 67) compared to matched healthy controls (HCs; = 88). Compared with HCs, the structural covariance networks of patients with DPN showed an increased characteristic path length, clustering coefficient, sigma, transitivity, and modularity, suggestive of inefficient global integration and increased local segregation. These findings may improve our understanding of the pathophysiological mechanisms underlying alterations in the central nervous system of patients with DPN from the perspective of large-scale structural brain networks.
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http://dx.doi.org/10.3389/fnins.2020.585588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746555PMC
December 2020

Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact.

Cell 2020 11;183(5):1185-1201.e20

The University of North Carolina at Chapel Hill, NC 27599, USA.

Spaceflight is known to impose changes on human physiology with unknown molecular etiologies. To reveal these causes, we used a multi-omics, systems biology analytical approach using biomedical profiles from fifty-nine astronauts and data from NASA's GeneLab derived from hundreds of samples flown in space to determine transcriptomic, proteomic, metabolomic, and epigenetic responses to spaceflight. Overall pathway analyses on the multi-omics datasets showed significant enrichment for mitochondrial processes, as well as innate immunity, chronic inflammation, cell cycle, circadian rhythm, and olfactory functions. Importantly, NASA's Twin Study provided a platform to confirm several of our principal findings. Evidence of altered mitochondrial function and DNA damage was also found in the urine and blood metabolic data compiled from the astronaut cohort and NASA Twin Study data, indicating mitochondrial stress as a consistent phenotype of spaceflight.
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http://dx.doi.org/10.1016/j.cell.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870178PMC
November 2020

Structural and functional brain signatures of endurance runners.

Brain Struct Funct 2021 Jan 7;226(1):93-103. Epub 2020 Nov 7.

Department of Physical Education, Shenzhen University, Shenzhen, 518060, China.

Although endurance running (ER) seems to be a simple repetitive exercise, good ER performance also requires and relies on multiple cognitive and motor control processes. Most of previous neuroimaging studies on ER were conducted using a single MRI modality, yet no multimodal study to our knowledge has been performed in this regard. In this study, we used multimodal MRI data to investigate the brain structural and functional differences between endurance runners (n = 22; age = 26.27 ± 6.07 years; endurance training = 6.23 ± 2.41 years) and healthy controls (HCs; n = 20; age = 24.60 ± 4.14 years). Compared with the HCs, the endurance runners showed greater gray matter volume (GMV) and cortical surface area in the left precentral gyrus, which at the same time had higher functional connectivity (FC) with the right postcentral and precentral gyrus. Subcortically, the endurance runners showed greater GMV in the left hippocampus and regional inflation in the right hippocampus. Using the bilateral hippocampi as seeds, further seed-based FC analyses showed higher hippocampal FC with the supplementary motor area, middle cingulate cortex, and left posterior lobe of the cerebellum. Moreover, compared with the HCs, the endurance runners also showed higher fractional anisotropy in several white matter regions, involving the corpus callosum, left internal capsule, left corona radiata, left external capsule, left posterior lobe of cerebellum and bilateral precuneus. Taken together, our findings provide several lines of evidence for the brain structural and functional differences between endurance runners and HCs. The current data suggest that these brain characteristics may have arisen as a result of regular ER training; however, whether they represent the neural correlates underlying the good ER performances of the endurance runners requires further investigations.
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http://dx.doi.org/10.1007/s00429-020-02170-yDOI Listing
January 2021

XACT-Seq Comprehensively Defines the Promoter-Position and Promoter-Sequence Determinants for Initial-Transcription Pausing.

Mol Cell 2020 09 3;79(5):797-811.e8. Epub 2020 Aug 3.

Department of Genetics, Rutgers University, Piscataway, NJ 08854, USA; Waksman Institute, Rutgers University, Piscataway, NJ 08854, USA. Electronic address:

Pausing by RNA polymerase (RNAP) during transcription elongation, in which a translocating RNAP uses a "stepping" mechanism, has been studied extensively, but pausing by RNAP during initial transcription, in which a promoter-anchored RNAP uses a "scrunching" mechanism, has not. We report a method that directly defines the RNAP-active-center position relative to DNA with single-nucleotide resolution (XACT-seq; "crosslink-between-active-center-and-template sequencing"). We apply this method to detect and quantify pausing in initial transcription at 4 (∼4,000,000) promoter sequences in vivo in Escherichia coli. The results show initial-transcription pausing can occur in each nucleotide addition during initial transcription, particularly the first 4 to 5 nucleotide additions. The results further show initial-transcription pausing occurs at sequences that resemble the consensus sequence element for transcription-elongation pausing. Our findings define the positional and sequence determinants for initial-transcription pausing and establish initial-transcription pausing is hard coded by sequence elements similar to those for transcription-elongation pausing.
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http://dx.doi.org/10.1016/j.molcel.2020.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484426PMC
September 2020

Scedar: A scalable Python package for single-cell RNA-seq exploratory data analysis.

PLoS Comput Biol 2020 04 27;16(4):e1007794. Epub 2020 Apr 27.

Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.

In single-cell RNA-seq (scRNA-seq) experiments, the number of individual cells has increased exponentially, and the sequencing depth of each cell has decreased significantly. As a result, analyzing scRNA-seq data requires extensive considerations of program efficiency and method selection. In order to reduce the complexity of scRNA-seq data analysis, we present scedar, a scalable Python package for scRNA-seq exploratory data analysis. The package provides a convenient and reliable interface for performing visualization, imputation of gene dropouts, detection of rare transcriptomic profiles, and clustering on large-scale scRNA-seq datasets. The analytical methods are efficient, and they also do not assume that the data follow certain statistical distributions. The package is extensible and modular, which would facilitate the further development of functionalities for future requirements with the open-source development community. The scedar package is distributed under the terms of the MIT license at https://pypi.org/project/scedar.
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http://dx.doi.org/10.1371/journal.pcbi.1007794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217489PMC
April 2020

Brain Functional Specialization Is Enhanced Among Tai Chi Chuan Practitioners.

Arch Phys Med Rehabil 2020 07 25;101(7):1176-1182. Epub 2020 Feb 25.

Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China. Electronic address:

Objective: To investigate the effect of long-term Tai Chi Chuan (TCC) practice on practitioners' brain functional specialization compare with the TCC novices.

Design: A cross-sectional study.

Setting: A psychology Institute.

Participants: TCC practitioners (N=22) (52.4±6.8y; 7 men; educated years: 12.18±3.03y) and 18 healthy adults (54.8±6.8y; 8 men; education years: 11.78±2.90y) matched by age, sex, and education were enrolled.

Main Outcome Measures: Participants underwent functional magnetic resonance imaging scanning and cognitive test to measure the differences in functional specialization and cognitive function. Functional specialization was evaluated by voxel-mirrored homotopic connectivity (VMHC) method.

Results: Lower middle frontal gyrus VMHC in TCC practitioners compared to controls. For TCC practitioners, the longer they practice, the lower their VMHC in precentral and precuneus. TCC practitioners showed better cognition performance.

Conclusions: Changed VMHC indicated that TCC practice could enhance functional specialization in the middle frontal cortex of practitioners, which may be associated with higher-order cognitive ability.
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http://dx.doi.org/10.1016/j.apmr.2020.02.005DOI Listing
July 2020

Sensorimotor and pain-related alterations of the gray matter and white matter in Type 2 diabetic patients with peripheral neuropathy.

Hum Brain Mapp 2020 02 29;41(3):710-725. Epub 2019 Oct 29.

Department of Radiology, Xiangya Hospital, Central South University, Changsha, China.

Although diabetic peripheral neuropathy (DPN) has long been considered a disease of the peripheral nervous system, recent neuroimaging studies have shown that alterations in the central nervous system may play a crucial role in its pathogenesis. Here, we used surface-based morphometry (SBM) and tract-based spatial statistics (TBSS) to investigate gray matter (GM) and white matter (WM) differences between patients with DPN (n = 67, 44 painless and 23 painful) and healthy controls (HCs; n = 88). Compared with HCs, patients with DPN exhibited GM abnormalities in the pre- and postcentral gyrus and in several deep GM nuclei (caudate, putamen, medial pallidum, thalamus, and ventral nuclear). They also exhibited altered WM tracts (corticospinal tract, spinothalamic tract, and thalamocortical projecting fibers). These findings suggest impaired motor and somatosensory pathways in DPN. Further, patients with DPN (particularly painful DPN) exhibited morphological differences in the cingulate, insula, prefrontal cortex, and thalamus, as well as impaired WM integrity in periaqueductal WM and internal and external capsules. This suggests pain-perception/modulation pathways are altered in painful DPN. Intermodal correlation analyses found that the morphological indices of the brain regions identified by the SBM analysis were significantly correlated with the fractional anisotropy of brain regions identified by the TBSS analysis, suggesting that the GM and WM alterations were tightly coupled. Overall, our study showed sensorimotor and pain-related GM and WM alterations in patients with DPN, which might be involved in the development of DPN.
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http://dx.doi.org/10.1002/hbm.24834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268085PMC
February 2020

Chemotherapy Potentially Facilitates the Occurrence of Radiation Encephalopathy in Patients With Nasopharyngeal Carcinoma Following Radiotherapy: A Multiparametric Magnetic Resonance Imaging Study.

Front Oncol 2019 3;9:567. Epub 2019 Jul 3.

Department of Radiology, Xiangya Hospital, Central South University, Changsha, China.

Radiation encephalopathy (RE) is deemed to be a disease induced only by radiotherapy (RT), with the effects of chemotherapeutic agents on the brains of nasopharyngeal carcinoma (NPC) patients being largely overlooked. In this study, we investigated structural and functional brain alterations in NPC patients following RT with or without chemotherapy. Fifty-six pre-RT, 37 post-RT, and 108 post-CCRT (concomitant chemo-radiotherapy) NPC patients were enrolled in this study. A surface-based local gyrification index (LGI) was obtained from high resolution MRI and was used to evaluate between-group differences in cortical folding. Seed-based functional connectivity (FC) analysis of resting-state fMRI data was also conducted to investigate the functional significance of the cortical folding alterations. Compared with the Pre-RT group, patients in the Post-CCRT group showed LGI reductions in widespread brain regions including the bilateral temporal lobes, insula, frontal lobes, and parietal lobes. Compared with the Post-RT group, patients in the Post-CCRT group showed LGI reductions in the right insula, which extended to the adjacent frontal lobe. Seed-based FC analysis showed that patients in the Post-CCRT group had lower FC between the insula and the left middle frontal gyrus than patients in the Pre-RT group. The follow-up results showed that patients in the Post-CCRT group had a much higher RE incidence rate (20.4%) than patients in the Post-RT group (2.7%; = 0.01). These findings indicate that chemotherapy potentially facilitated the occurrence of RE in NPC patients who underwent radiotherapy.
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http://dx.doi.org/10.3389/fonc.2019.00567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6618298PMC
July 2019

DNA-Functionalized Metal-Organic Framework: Cell Imaging, Targeting Drug Delivery and Photodynamic Therapy.

Inorg Chem 2019 May 10;58(10):6593-6596. Epub 2019 May 10.

Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, School of Chemistry and Chemical Engineering , Linyi University , Linyi 276000 , Shandong , P. R. China.

Here, DNA-functionalized nanoscale PCN-224 is established with the aptamer of A549 lung cancer cells. The aptamer was modified with carboxyl and fluorescein at the two terminals. When touching the A549 cells, [email protected] can trace tumor cells and present good targeting therapy by the combination of chemotherapy and photodynamic therapy. This facile aptamer functionalization of PCN-224 offers an opportunity to develop metal-organic framework-based target-directed therapy and biosensors.
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http://dx.doi.org/10.1021/acs.inorgchem.9b00734DOI Listing
May 2019

Precentral degeneration and cerebellar compensation in amyotrophic lateral sclerosis: A multimodal MRI analysis.

Hum Brain Mapp 2019 08 24;40(12):3464-3474. Epub 2019 Apr 24.

Department of Radiology, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing, People's Republic of China.

Amyotrophic lateral sclerosis (ALS) is a progressive and intractable neurodegenerative disease of human motor system characterized by progressive muscular weakness and atrophy. A considerable body of research has demonstrated significant structural and functional abnormalities of the primary motor cortex in patients with ALS. In contrast, much less attention has been paid to the abnormalities of cerebellum in this disease. Using multimodal magnetic resonance imagining data of 60 patients with ALS and 60 healthy controls, we examined changes in gray matter volume (GMV), white matter (WM) fractional anisotropy (FA), and functional connectivity (FC) in patients with ALS. Compared with healthy controls, patients with ALS showed decreased GMV in the left precentral gyrus and increased GMV in bilateral cerebellum, decreased FA in the left corticospinal tract and body of corpus callosum, and decreased FC in multiple brain regions, involving bilateral postcentral gyrus, precentral gyrus and cerebellum anterior lobe, among others. Meanwhile, we found significant intermodal correlations among GMV of left precentral gyrus, FA of altered WM tracts, and FC of left precentral gyrus, and that WM microstructural alterations seem to play important roles in mediating the relationship between GMV and FC of the precentral gyrus, as well as the relationship between GMVs of the precentral gyrus and cerebellum. These findings provided evidence for the precentral degeneration and cerebellar compensation in ALS, and the involvement of WM alterations in mediating the relationship between pathologies of the primary motor cortex and cerebellum, which may contribute to a better understanding of the pathophysiology of ALS.
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http://dx.doi.org/10.1002/hbm.24609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865414PMC
August 2019

The Pediatric Cell Atlas: Defining the Growth Phase of Human Development at Single-Cell Resolution.

Dev Cell 2019 04 28;49(1):10-29. Epub 2019 Mar 28.

Environmental Genomics and Systems Biology Division, E. O. Lawrence Berkeley National Laboratory, Berkeley, CA, USA.

Single-cell gene expression analyses of mammalian tissues have uncovered profound stage-specific molecular regulatory phenomena that have changed the understanding of unique cell types and signaling pathways critical for lineage determination, morphogenesis, and growth. We discuss here the case for a Pediatric Cell Atlas as part of the Human Cell Atlas consortium to provide single-cell profiles and spatial characterization of gene expression across human tissues and organs. Such data will complement adult and developmentally focused HCA projects to provide a rich cytogenomic framework for understanding not only pediatric health and disease but also environmental and genetic impacts across the human lifespan.
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http://dx.doi.org/10.1016/j.devcel.2019.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616346PMC
April 2019

Abnormal topological organization of structural covariance networks in amyotrophic lateral sclerosis.

Neuroimage Clin 2019 30;21:101619. Epub 2018 Nov 30.

Department of Radiology, Chongqing University Cancer Hospital, Chongqing Cancer Institute, Chongqing Cancer Hospital, Chongqing 400030, PR China; Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing Cancer Institute, Chongqing Cancer Hospital, Chongqing 400044, PR China. Electronic address:

Neuroimaging studies of patients with amyotrophic lateral sclerosis (ALS) have shown widespread alterations in structure, function, and connectivity in both motor and non-motor brain regions, suggesting multi-systemic neurobiological abnormalities that might impact large-scale brain networks. Here, we examined the alterations in the topological organization of structural covariance networks of ALS patients (N = 60) compared with normal controls (N = 60). We found that structural covariance networks of ALS patients showed a consistent rearrangement towards a regularized architecture evidenced by increased path length, clustering coefficient, small-world index, and modularity, as well as decreased global efficiency, suggesting inefficient global integration and increased local segregation. Locally, ALS patients showed decreased nodal degree and betweenness in the gyrus rectus and/or Heschl's gyrus, and increased betweenness in the supplementary motor area, triangular part of the inferior frontal gyrus, supramarginal gyrus and posterior cingulate cortex. In addition, we identified a different number and distribution of hubs in ALS patients, showing more frontal and subcortical hubs than in normal controls. In conclusion, we reveal abnormal topological organization of structural covariance networks in ALS patients, and provide network-level evidence for the concept that ALS is a multisystem disorder with a cerebral involvement extending beyond the motor areas.
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http://dx.doi.org/10.1016/j.nicl.2018.101619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411656PMC
December 2019

CapZyme-Seq Comprehensively Defines Promoter-Sequence Determinants for RNA 5' Capping with NAD.

Mol Cell 2018 05 19;70(3):553-564.e9. Epub 2018 Apr 19.

Department of Genetics and Waksman Institute, Rutgers University, Piscataway, NJ 08854, USA. Electronic address:

Nucleoside-containing metabolites such as NAD can be incorporated as 5' caps on RNA by serving as non-canonical initiating nucleotides (NCINs) for transcription initiation by RNA polymerase (RNAP). Here, we report CapZyme-seq, a high-throughput-sequencing method that employs NCIN-decapping enzymes NudC and Rai1 to detect and quantify NCIN-capped RNA. By combining CapZyme-seq with multiplexed transcriptomics, we determine efficiencies of NAD capping by Escherichia coli RNAP for ∼16,000 promoter sequences. The results define preferred transcription start site (TSS) positions for NAD capping and define a consensus promoter sequence for NAD capping: HRRASWW (TSS underlined). By applying CapZyme-seq to E. coli total cellular RNA, we establish that sequence determinants for NCIN capping in vivo match the NAD-capping consensus defined in vitro, and we identify and quantify NCIN-capped small RNAs (sRNAs). Our findings define the promoter-sequence determinants for NCIN capping with NAD and provide a general method for analysis of NCIN capping in vitro and in vivo.
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http://dx.doi.org/10.1016/j.molcel.2018.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935523PMC
May 2018

I radiolabeled immune albumin nanospheres loaded with doxorubicin for in vivo combinatorial therapy.

J Labelled Comp Radiopharm 2018 04 6;61(4):362-369. Epub 2018 Feb 6.

Nuclear Medicine Department, the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, China.

For the purpose of providing new insights for high-efficiency radiochemotherapy of hepatoma, a radioimmunotherapy and chemotherapy combinatorial therapy albumin nanospheres I-antiAFPMcAb-DOX-BSA-NPs was designed and prepared. It was obtained in a high radiolabeling yield approximately 65% with the radiochemical purity of over 98%. The transmission electron microscope showed that the nanospheres obtained in good monodispersion with a diameter of approximately 230 nm. The doxorubicin (DOX) loading capacity of the DOX-BSA-NPs nanoparticles was determined to be approximately 180 μg/mg and 95.79 ± 3.89%. DOX was released gradually in 6 days. In vivo tumor-growth inhibition experiments showed that after treating with I-antiAFPMcAb-DOX-BSA-NPs for 14 days, the tumor volume decreased more obvious than that of other 2 time points and the control groups. All the results indicated that the radiolabeled immune albumin nanospheres I-antiAFPMcAb-DOX-BSA-NPs could significantly inhibit the hepatoma tumor growth with the strategy of combinatorial radioimmunotherapy and chemotherapy.
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http://dx.doi.org/10.1002/jlcr.3593DOI Listing
April 2018

Structural and functional abnormalities of the insular cortex in trigeminal neuralgia: a multimodal magnetic resonance imaging analysis.

Pain 2018 03;159(3):507-514

Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People's Republic of China.

Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by intense, lancinating attacks of facial pain. Increasing evidence suggests that TN is accompanied by abnormalities in brain morphology, white matter microstructure, and function. However, whether these abnormalities are linked or reflect independent etiologies remains unknown. Using multimodal magnetic resonance imaging data of 20 patients with TN and 21 healthy controls, we investigated cortical gyrification abnormalities, their relationships with abnormalities of the underlying white matter microstructure and gray matter morphology, as well as their functional significance in TN. Compared with controls, patients with TN showed significant local gyrification index (LGI) reductions predominantly in the left insular cortex, which were negatively correlated with pain intensity. In this cluster, patients with TN had concurrent cortical thickness reductions but unaltered cortical surface area. Meanwhile, LGI of this cluster was not correlated with overlying cortical thickness or surface area but was positively correlated with the fractional anisotropy of 2 nearby white matter clusters, suggesting that insular LGI reductions may be primarily driven by microstructural abnormalities of the underlying white matter tracts, rather than by abnormalities in cortical thickness and surface area. In addition, patients with TN exhibited increased insula functional connectivity to the left posterior cingulate cortex and thalamus, which was positively correlated with disease duration. These findings provide new evidence for the involvement of insular abnormalities in the pathophysiology of TN.
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http://dx.doi.org/10.1097/j.pain.0000000000001120DOI Listing
March 2018

Label-free Electrochemical Detection of ATP Based on Amino-functionalized Metal-organic Framework.

Sci Rep 2017 07 26;7(1):6500. Epub 2017 Jul 26.

Shandong Province Key Laboratory of Detection Technology for Tumor Makers, College of Chemistry and Chemical Engineering, Linyi University, Linyi, 276000, China.

A sensitive, selective and recyclable electrochemical sensor is designed for ATP detection based on amino-functionalized metal-organic framework. The functional MOF as the sensor is constructed by one-step synthesis Ce-MOF and sequentially modified on the Au electrode and conjugated with the aptamer of ATP. The presence of target ATP leads to the conformational change of aptamer strands and strong electrochemical impedance. The electrochemical sensor can detect ATP down to 5.6 nM with the linear range of 10 nm to 1000 μM. The present study is the first report on the use of MOF as an electrochemical sensor for ATP at nM level. This strategy has been successfully applied in detection of ATP in serum of cancer patients, which reveals its potential application in clinical diagnosis.
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http://dx.doi.org/10.1038/s41598-017-06858-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529508PMC
July 2017

Abnormal cortical-basal ganglia network in amyotrophic lateral sclerosis: A voxel-wise network efficiency analysis.

Behav Brain Res 2017 08 1;333:123-128. Epub 2017 Jul 1.

Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address:

Evidence suggests that dysfunctional cortical-basal ganglia (CBG) network plays important roles in the motor symptoms in amyotrophic lateral sclerosis (ALS). However, little effort has been made to investigate the functional abnormalities of CBG network in ALS. Here, we constructed voxel-wise CBG networks using the resting-state fMRI data of 20 patients with ALS and 21 normal controls, and characterized the differences of their efficiency parameters between the two groups. Compared to normal controls, patients with ALS exhibited decreased nodal efficiency in the right thalamus (THA), the left caudate (CAU) and the right precentral gyrus (preCG), and increased nodal efficiency in the left preCG. In the patient group, we observed a significant negative correlation between the nodal efficiency of the right preCG and disease progression rate. These results demonstrate that both ineffective information transfer and compensatory mechanisms are involved in the pathophysiological mechanism underlying the motor dysfunctions in patients with ALS. In summary, the present study provides a novel perspective on pathophysiological explanation for the motor symptoms in patients with ALS.
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http://dx.doi.org/10.1016/j.bbr.2017.06.050DOI Listing
August 2017

Size-dependent Effects of Gold Nanoparticles on Osteogenic Differentiation of Human Periodontal Ligament Progenitor Cells.

Theranostics 2017 6;7(5):1214-1224. Epub 2017 Mar 6.

Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.

Gold nanoparticles (AuNPs) have been reported to promote osteogenic differentiation of mesenchymal stem cells and osteoblasts, but little is known about their effects on human periodontal ligament progenitor cells (PDLPs). In this study, we evaluated the effects of AuNPs with various diameters (5, 13 and 45 nm) on the osteogenic differentiation of PDLPs and explored the underlying mechanisms. 5 nm AuNPs reduced the alkaline phosphatase activity, mineralized nodule formation and expression of osteogenic genes, while 13 and 45 nm AuNPs increased these osteogenic markers. Compared with 13 nm, 45 nm AuNPs showed more effective in promoting osteogenic differentiation. Meanwhile, autophagy was up-regulated by 13 and 45 nm AuNPs but blocked by 5 nm AuNPs, which corresponded with their effects on osteogenic differentiation and indicated that autophagy might be involved in this process. Furthermore, the osteogenesis induced by 45 nm AuNPs could be reversed by autophagy inhibitors (3-methyladenine and chloroquine). These findings revealed that AuNPs affected the osteogenic differentiation of PDLPs in a size-dependent manner with autophagy as a potential explanation, which suggested AuNPs with defined size could be a promising material for periodontal bone regeneration.
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http://dx.doi.org/10.7150/thno.17252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399588PMC
January 2018

Abnormalities in Structural Covariance of Cortical Gyrification in Parkinson's Disease.

Front Neuroanat 2017 7;11:12. Epub 2017 Mar 7.

Key Laboratory for Neuroinformation of the Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of ChinaChengdu, China; Center for Information in Medicine, University of Electronic Science and Technology of ChinaChengdu, China.

Although abnormal cortical morphology and connectivity between brain regions (structural covariance) have been reported in Parkinson's disease (PD), the topological organizations of large-scale structural brain networks are still poorly understood. In this study, we investigated large-scale structural brain networks in a sample of 37 PD patients and 34 healthy controls (HC) by assessing the structural covariance of cortical gyrification with local gyrification index (lGI). We demonstrated prominent small-world properties of the structural brain networks for both groups. Compared with the HC group, PD patients showed significantly increased integrated characteristic path length and integrated clustering coefficient, as well as decreased integrated global efficiency in structural brain networks. Distinct distributions of hub regions were identified between the two groups, showing more hub regions in the frontal cortex in PD patients. Moreover, the modular analyses revealed significantly decreased integrated regional efficiency in lateral Fronto-Insula-Temporal module, and increased integrated regional efficiency in Parieto-Temporal module in the PD group as compared to the HC group. In summary, our study demonstrated altered topological properties of structural networks at a global, regional and modular level in PD patients. These findings suggests that the structural networks of PD patients have a suboptimal topological organization, resulting in less effective integration of information between brain regions.
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http://dx.doi.org/10.3389/fnana.2017.00012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339339PMC
March 2017

Prefrontal dysconnectivity links to working memory deficit in first-episode schizophrenia.

Brain Imaging Behav 2018 Apr;12(2):335-344

Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.

Working memory (WM) deficit is a core feature of schizophrenia and is characterized by abnormal functional integration in the prefrontal cortex, including the dorsolateral prefrontal cortex (dLPFC), dorsal anterior cingulate cortex (dACC), and ventrolateral prefrontal cortex (vLPFC). However, the specific mechanism by which the abnormal neuronal circuits that involve these brain regions contribute to this deficit is still unclear. Therefore, this study focused on these regions and sought to answer which abnormal causal relationships in these regions can be linked to impaired WM in schizophrenia. We used spectral dynamic causal modeling to estimate directed (effective) connectivity between these regions based on resting-state functional magnetic resonance imaging data from healthy control (HC) subjects and patients with first-episode schizophrenia (FES). By comparing these effective connections in the controls and patients, we found that the effective connectivity from the dACC to the dLPFC and from the right dLPFC to the left vLPFC was weaker in the FES group than in the HC group. Furthermore, these effective connections displayed a positive correlation with WM performance in the HCs. However, in the FES patients, the effective connectivity from the dACC to the dLPFC was not correlated with WM performance, and the effective connectivity from the right dLPFC to the left vLPFC was negatively correlated with WM performance. These results could be explained by an aberrant top-down mechanism of WM processing and provide new evidence for the dysconnectivity hypothesis of schizophrenia.
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http://dx.doi.org/10.1007/s11682-017-9692-0DOI Listing
April 2018

NLRP3 p.Q705K and CARD8 p.C10X single nucleotide polymorphisms are not associated with susceptibility to rheumatoid arthritis: a meta-analysis.

Int J Rheum Dis 2017 Oct 9;20(10):1481-1491. Epub 2017 Feb 9.

Department of Immunology, Shandong University School of Medicine, Ji'nan, China.

Aim: Genetic factors have a substantial contribution to the pathogenesis of rheumatoid arthritis (RA). Single nucleotide polymorphisms of NLRP3 p.Q705K and CARD8 p.C10X are two gene mutations that have been linked to many diseases. Here we carried out a meta-analysis to identify their association with susceptibility to RA.

Method: Relevant studies were identified from databases, including PubMed, Cochrane Library, EMBase, Elsevier Science Direct, Web of Science, SpringerLink, and so on. Data extracted from selected studies were analyzed using the Version 12.0 STATA software. Pooled odds ratios (ORs) were calculated as the effect sizes for comparisons.

Results: In total, six case-control studies from five articles that contained 2705 RA patients and 2711 healthy controls were included. (i) The NLRP3 p.Q705K polymorphism in allelic model (OR = 0.908), genotypic models (OR1 = 0.786; OR2 = 0.916; OR3 = 0.729), dominant (OR = 0.909) and recessive models (OR = 0.778) were not associated with the risk of RA (all P > 0.05). (ii) The CARD8 p.C10X polymorphism in allelic model (OR = 0.995,), genotypic models (OR1 = 0.997; OR2 = 1.052; OR3 = 0.950), dominant (OR = 1.033) and recessive models (OR = 0.963) were not associated with the risk of RA (all P > 0.05). (iii) When compared with combined genotype CARD8/NLRP3 AA/CC, none of the other combined genotypes had significant pooled ORs (all P > 0.05). (iv) Individuals carrying at least one variant allele at each of the two loci showed no more susceptibility to RA than those carrying only wild-type alleles at both the NLRP3 p.Q705K and CARD8 p.C10X loci (OR = 1.056, P > 0.05).

Conclusion: NLRP3 p.Q705K and CARD8 p.C10X polymorphisms were not associated with the susceptibility to RA, separately or in combined forms.
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http://dx.doi.org/10.1111/1756-185X.13016DOI Listing
October 2017

Anti-4-1BB monoclonal antibodies attenuate concanavalin A-induced immune-mediated liver injury in mice.

Exp Ther Med 2016 Sep 24;12(3):1263-1268. Epub 2016 Jun 24.

Department of Rheumatology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.

Effective therapies for the treatment of immune-mediated liver disease are currently lacking. As a member of the tumor necrosis factor receptor superfamily, 4-1BB has a key role in T-cell activation and has been implicated in the development of autoimmune disorders. The purpose of the present study was to evaluate the potential therapeutic or preventive function of an anti-4-1BB monoclonal antibody (mAb) in a mouse model of concanavalin (Con) A-induced immune-mediated liver injury. A mouse model of immune-mediated liver injury was established by tail vein injection of Con A (20 mg/kg). 4-1BB mAb (100 µg), with or without methylprednisolone (MEP; 3 mg/kg), was intraperitoneally injected into the tail vein 2 h prior to or 2 h following Con A injection. Con A induced marked hepatocyte necrosis, significantly reduced CD 4/CD25 T-cell levels, and increased the serum levels of aspartate transaminase (AST) and alanine transaminase (ALT), in addition to the percentage of 4-1BB T-cells, compared with the control (all P<0.05). The administration of 4-1BB mAb prior to or following Con A injection was able to attenuate Con A-induced liver tissue damage and significantly reduce serum AST and ALT levels (P<0.05). A combination of MEP and 4-1BB mAb further reduced serum AST and ALT levels, compared with either treatment alone. In addition, administration of 4-1BB mAb and MEP alone or in combination significantly increased CD4/CD25 T-cell levels, compared with the control (P<0.05). These results suggested that 4-1BB mAb was able to attenuate liver injury and preserve liver function in a mouse model of Con A-induced immune-mediated liver injury by promoting the expansion of CD4/CD25 T-cells. Furthermore, a combination of 4-1BB mAb with MEP was associated with greater beneficial effects than either treatment alone. The clinical significance of 4-1BB mAb in immune-mediated liver disease remains to be elucidated in future studies.
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http://dx.doi.org/10.3892/etm.2016.3503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998111PMC
September 2016
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