Publications by authors named "Shuo Han"

147 Publications

Tang Luo Ning, a Traditional Chinese Compound Prescription, Ameliorates Schwannopathy of Diabetic Peripheral Neuropathy Rats by Regulating Mitochondrial Dynamics and .

Front Pharmacol 2021 14;12:650448. Epub 2021 May 14.

School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.

Tang Luo Ning (TLN), a traditional Chinese compound prescription, has been used clinically to treat diabetic peripheral neuropathy (DPN) in China. However, the exact mechanisms remain unclear. The objective of this study is to unravel the effects of TLN on mitochondrial dynamics of DPN in streptozotocin-induced rat models and Schwann cells cultured in 150 mM glucose. Mitochondrial function was determined by Ca and ATP levels of streptozotocin (STZ)-induced DPN rats and mitochondria structure, mitochondrial membrane potential (MMP), and mtDNA of high glucose incubated SCs. Mitochondrial dynamics protein including mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), optic atrophy 1 (Opa1), and dynamin-related protein 1 (Drp1) were investigated using Western blot or immunofluorescence. Myelin basic protein (MBP), myelin protein zero (MPZ), and sex-determining region Y (SRY)-box 10 (Sox10) were measured to represent schwannopathy. Our results showed that TLN increased ATP levels (0.38 of model, 0.69 of HTLN, 0.61 of LTLN, <0.01; 0.52 of 150 mM glucose, 1.00 of 10% TLN, <0.01, 0.94 of 1% TLN, <0.05), MMP (0.56 of 150 mM glucose, <0.01, 0.75 of 10% TLN, <0.05, 0.83 of 1% TLN, <0.01), and mtDNA (0.32 of 150 mM glucose, 0.43 of 10% TLN, <0.01) while decreased Ca (1.54 of model, 1.06 of HTLN, 0.96 of LTLN, <0.01) to improve mitochondrial function and . TLN helps maintain balance of mitochondrial dynamics: it reduces the mitochondria number (1.60 of 150 mM glucose, 1.10 of 10% TLN, <0.01) and increases the mitochondria coverage (0.51 of 150 mM glucose, 0.80 of 10% TLN, 0.87 of 1% TLN, <0.01), mitochondrial network size (0.51 of 150 mM glucose, 0.95 of 10% TLN, 0.94 of 1% TLN, <0.01), and branch length (0.63 of 150 mM glucose, <0.01, 0.73 of 10% TLN, <0.05, 0.78 of 1% TLN, <0.01). Further, mitochondrial dynamics-related Mfn1 (0.47 of model, 0.82 of HTLN, 0.77 of LTLN, <0.01; 0.42 of 150 mM glucose, 0.56 of 10% TLN, 0.57 of 1% TLN, <0.01), Mfn2 (0.40 of model, 0.84 of HTLN, 0.63 of LTLN, <0.01; 0.46 of 150 mM glucose, 1.40 of 10% TLN, 1.40 of 1% TLN, <0.01), and Opa1 (0.58 of model, 0.71 of HTLN, 0.90 of LTLN, <0.01; 0.69 of 150 mM glucose, 0.96 of 10% TLN, 0.98 of 1% TLN, <0.05) were increased, while Drp1 (1.39 of model, 0.96 of HTLN, 1.18 of LTLN, <0.01; 1.70 of 150 mM glucose, 1.20 of 10% TLN, 1.10 of 1% TLN, <0.05), phosphorylated Drp1 (2.61 of model, 1.44 of HTLN, <0.05; 2.80 of 150 mM glucose, 1.50 of 10% TLN, 1.30 of 1% TLN, <0.01), and Drp1 located in mitochondria (1.80 of 150 mM glucose, 1.00 of 10% TLN, <0.05) were decreased after treatment with TLN. Additionally, TLN improved schwannopathy by increasing MBP (0.50 of model, 1.05 of HTLN, 0.94 of HTLN, <0.01; 0.60 of 150 mM glucose, 0.78 of 10% TLN, <0.01, 0.72 of 1% TLN, <0.05), Sox101 (0.41 of model, 0.99 of LTLN, <0.01; 0.48 of 150 mM glucose, 0.65 of 10% TLN, <0.05, 0.69 of 1% TLN, <0.01), and MPZ (0.48 of model, 0.66 of HTLN, 0.55 of HTLN, <0.01; 0.60 of 150 mM glucose, 0.78 of 10% TLN, <0.01, 0.75 of 1% TLN, <0.05) expressions. In conclusion, our study indicated that TLN's function on DPN may link to the improvement of the mitochondrial dynamics, which provides scientific evidence for the clinical application.
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http://dx.doi.org/10.3389/fphar.2021.650448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160508PMC
May 2021

A Anchoring Technique Using Long Bent Rods for Open Reduction of Thoracolumbar Dislocation.

Clin Spine Surg 2021 May 24. Epub 2021 May 24.

Department of Spinal Surgery, The Second Hospital of Tangshan, Tangshan, People's Republic of China.

Objective: The purpose of this study was to evaluate the effectiveness of a novel surgical open reduction method for thoracolumbar dislocation.

Materials And Methods: This study included a total of 15 patients of thoracolumbar dislocation. All patients underwent posterior thoracolumbar open reduction and fixation using this technique. Preoperative x-ray, computed tomography (CT), and magnetic resonance imaging were used to evaluate the dislocation. The American Spinal Injury Association grade of spinal cord injury before and afer the operation were record. All patients were followed up for 2 years, and x-ray, CT were used to observe postoperative reduction and fusion.

Results: Postoperative x-ray and CT images of all patients indicated good recovery of the spinal sequence, and no neurological deterioration or surgically related complications occurred. All patients were followed up for 2 years, no patients were lost to follow-up. During the follow-up period, x-ray and CT images showed no complications related to internal fixation such as fracture and loosening of screws and rods were found.

Conclusion: A anchoring technique using long bent rods is a safe, simple, accurate, and easy to replicate and implement method, which can be applied in the surgical treatment for thoracolumbar dislocation.
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http://dx.doi.org/10.1097/BSD.0000000000001198DOI Listing
May 2021

Iterative reconstruction algorithm based on discriminant adaptive-weighted TV regularization for fibrous biological tissues using in-line X-ray phase-contrast imaging.

Biomed Opt Express 2021 Apr 29;12(4):2460-2483. Epub 2021 Mar 29.

School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin 300070, China.

In-line X-ray phase-contrast computed tomography (IL-PCCT) can produce high-contrast and high-resolution images of biological samples, and it has a great advantage with regard to imaging the microstructures and morphologies of fibrous biological tissues (FBTs). Filtered back projection (FBP) is widely used in ILPCCT. However, it requires long scanning times and high radiation doses to produce high-quality CT images, and this restricts its applicability in biomedical and preclinical studies on FBTs. To solve this problem, a novel IL-PCCT reconstruction algorithm is proposed to decrease the radiation dose by reducing the number of projections and reconstruct high-quality CT images of FBTs. The proposed algorithm incorporates the FBP method into the iterative reconstruction framework. Considering the area types and anisotropic edge properties of FBTs, a discriminant adaptive-weighted total variation model is introduced to optimize the intermediate reconstructed images. A fibrous phantom simulation and real experiment were performed to assess the performance of the proposed algorithm. Simulation and experimental results demonstrated that the proposed algorithm is an effective IL-PCCT reconstruction method for FBTs with incomplete projection data, and it has a great ability to suppress artifacts and preserve the edges of fibrous structures.
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http://dx.doi.org/10.1364/BOE.418898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086461PMC
April 2021

Myocardin‑related transcription factor A nuclear translocation contributes to mechanical overload‑induced nucleus pulposus fibrosis in rats with intervertebral disc degeneration.

Int J Mol Med 2021 Jul 13;48(1). Epub 2021 May 13.

Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qing'dao, Shandong 266000, P.R. China.

Previous studies have reported that the Ras homolog family member A (RhoA)/myocardin‑related transcription factor A (MRTF‑A) nuclear translocation axis positively regulates fibrogenesis induced by mechanical forces in various organ systems. The aim of the present study was to determine whether this signaling pathway was involved in the pathogenesis of nucleus pulposus (NP) fibrosis induced by mechanical overload during the progression of intervertebral disc degeneration (IVDD) and to confirm the alleviating effect of an MRTF‑A inhibitor in the treatment of IVDD. NP cells (NPCs) were cultured on substrates of different stiffness (2.9 and 41.7 KPa), which mimicked normal and overloaded microenvironments, and were treated with an inhibitor of MRTF‑A nuclear import, CCG‑1423. In addition, bipedal rats were established by clipping the forelimbs of rats at 1 month and gradually elevating the feeding trough, and in order to establish a long‑term overload‑induced model of IVDD, and their intervertebral discs were injected with CCG‑1423 . Cell viability was determined by Cell Counting Kit‑8 assay, and protein expression was determined by western blotting, immunofluorescence and immunohistochemical staining. The results demonstrated that the viability of NPCs was not affected by the application of force or the inhibitor. In NPCs cultured on stiff matrices, MRTF‑A was mostly localized in the nucleus, and the expression levels of fibrotic proteins, including type I collagen, connective tissue growth factor and α‑smooth muscle cell actin, were upregulated compared with those in NPCs cultured on soft matrices. The levels of these proteins were reduced by CCG‑1423 treatment. In rats, 6 months of upright posture activated MRTF‑A nuclear‑cytoplasmic trafficking and fibrogenesis in the NP and induced IVDD; these effects were alleviated by CCG‑1423 treatment. In conclusion, the results of the present study demonstrated that the RhoA/MRTF‑A translocation pathway may promote mechanical overload‑induced fibrogenic activity in NP tissue and partially elucidated the molecular mechanisms underlying the occurrence of IVDD.
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http://dx.doi.org/10.3892/ijmm.2021.4956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121555PMC
July 2021

Metabolomics screening of serum biomarkers for occupational exposure of titanium dioxide nanoparticles.

Nanotoxicology 2021 May 7:1-18. Epub 2021 May 7.

Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China.

Although nanotoxicology studies have shown that respiratory exposure of titanium dioxide nanoparticles (TiO NPs) could induce adverse health effects, limited biomarkers associated with occupational exposure of TiO NPs were reported. The purpose of this study is to screen serum biomarkers among workers occupationally exposed to TiO NPs using metabolomics. Compared with the control group, a total of 296 serum metabolites were differentially expressed in the TiO NPs-exposed group, of which the relative expression of 265 metabolites increased, and the remaining 31 decreased. Three machine learning methods including random forest (RF), support vector machines (SVM), and boruta screened eight potential biomarkers and simultaneously selected a metabolite, Liquoric acid. Through multiple linear regression analysis to adjust the influence of confounding factors such as gender, age, BMI, smoking and drinking, occupational exposure to TiO NPs was significantly related to the relative expression of the eight potential biomarkers. Meanwhile, the receiver operating characteristic curves (ROCs) of these potential biomarkers had good sensitivity and specificity. These potential biomarkers were related to lipid peroxidation, and had biological basis for occupational exposure to TiO NPs. Therefore, it was demonstrated that the serum metabolites represented by Liquoric acid were good biomarkers of occupational exposure to TiO NPs.
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http://dx.doi.org/10.1080/17435390.2021.1921872DOI Listing
May 2021

Genome sequencing sheds light on the contribution of structural variants to Brassica oleracea diversification.

BMC Biol 2021 May 5;19(1):93. Epub 2021 May 5.

National Engineering Research Center for Vegetables, Beijing Academy of Agriculture and Forestry Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops (North China), Beijing Key Laboratory of Vegetable Germplasm Improvement, Beijing, 100097, China.

Background: Brassica oleracea includes several morphologically diverse, economically important vegetable crops, such as the cauliflower and cabbage. However, genetic variants, especially large structural variants (SVs), that underlie the extreme morphological diversity of B. oleracea remain largely unexplored.

Results: Here we present high-quality chromosome-scale genome assemblies for two B. oleracea morphotypes, cauliflower and cabbage. Direct comparison of these two assemblies identifies ~ 120 K high-confidence SVs. Population analysis of 271 B. oleracea accessions using these SVs clearly separates different morphotypes, suggesting the association of SVs with B. oleracea intraspecific divergence. Genes affected by SVs selected between cauliflower and cabbage are enriched with functions related to response to stress and stimulus and meristem and flower development. Furthermore, genes affected by selected SVs and involved in the switch from vegetative to generative growth that defines curd initiation, inflorescence meristem proliferation for curd formation, maintenance and enlargement, are identified, providing insights into the regulatory network of curd development.

Conclusions: This study reveals the important roles of SVs in diversification of different morphotypes of B. oleracea, and the newly assembled genomes and the SVs provide rich resources for future research and breeding.
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http://dx.doi.org/10.1186/s12915-021-01031-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097969PMC
May 2021

Evaluating the Effect of Government Emission Reduction Policy: Evidence from Demonstration Cities in China.

Int J Environ Res Public Health 2021 04 27;18(9). Epub 2021 Apr 27.

KoGuan School of Law, Shanghai Jiao Tong University, Shanghai 200030, China.

The effectiveness of government environmental policies is pivotal to environmental quality and provides the reference for further policy design. This paper estimates the effect of comprehensive demonstration of fiscal policy for ECER (Energy Conservation and Emission Reduction) on pollution emissions in Chinese cities with the sample period from 2003 to 2016, which is an important practice for policy integration. We find that this policy reduces the industrial SO (sulfur dioxide) emission by 23.8% on average and the industrial wastewater emission by 17.5% on average. This policy, implemented by Chinese government, has effectively achieved its target for emission reduction. A series of robustness checks are also conducted to verify the baseline results. Mechanism analysis indicates that this policy has the effect by the change in the industry structure and the enhancement of fiscal capacity, especially the capacity of fiscal revenue. Some policy recommendations, such as laying emphasis on the policy integration, integrating the financial resources of governments and expanding the demonstration effect, are proposed in order to facilitate green development in Chinese cities.
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http://dx.doi.org/10.3390/ijerph18094649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124879PMC
April 2021

The technical feasibility and preliminary results of minimally invasive endoscopic-TLIF based on electromagnetic navigation: a case series.

BMC Surg 2021 Mar 20;21(1):149. Epub 2021 Mar 20.

Department of Spine Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China.

Background: Uniportal full endoscopic posterolateral transforaminal lumbar interbody fusion (Endo-TLIF) with percutaneous pedicle screw fixation is a promising, minimally invasive method for the treatment of lumbar spondylolisthesis. However, repeated radiation exposure from X-rays and the steep learning curve remain to be improved.

Methods: This retrospective study explored the effects of electromagnetic navigation on improving Endo-TLIF with percutaneous pedicle screw fixation. Clinical information from 42 patients who had received Endo-TLIF with percutaneous pedicle screw fixation from May 2019 to November 2020 was analyzed retrospectively. The procedures were assisted under electromagnetic navigation. The rate of adjustment for guide wires, frequency of X-ray exposure, operative time, accuracy of pedicle screw location, and clinical outcomes were recorded.

Results: The mean follow-up for 42 patients was 11.9 ± 3.1 months. The mean age of the patients was 56.1 ± 9.26 years, with a female/male ratio of 25:17. According to postoperative CT scans and 3D reconstructions, the excellent and good rate of pedicle screws was 96.4%. The rate of adjustment for guide wires under the assistance of electromagnetic navigation was 1.78%, and the frequency of X-ray exposure was 8.27 ± 1.83. The operative time was 167.25 ± 28.16 min, including the duration of guide wire insertion (14.63 ± 5.45 min) and duration of decompression and cage placement (75.43 ± 13.97 min). The duration of hospitalization after operation was 2.59 ± 1.16 days. The preoperative VAS score was 7.51 ± 1.91, and the preoperative ODI was 82.42 ± 8.7%. At the last follow-up, the VAS score was 2.09 ± 0.59, and the ODI was 11.09 ± 3.2%. There were statistically significant improvements in the VAS score and ODI in all patients at the follow-up (p < 0.05).

Conclusions: Electromagnetic navigation can provide accurate positioning and guidance in real time, which improves the surgical efficiency of percutaneous pedicle screw placement and endoscopic decompression in Endo-TLIF with reduced radiation exposures.
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http://dx.doi.org/10.1186/s12893-021-01148-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981827PMC
March 2021

Nanoporous and Highly Thermal Conductive Thin Film of Single-Crystal Covalent Organic Frameworks Ribbons.

J Am Chem Soc 2021 Mar 25;143(10):3927-3933. Epub 2021 Feb 25.

Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, School of Chemistry, and State Key Laboratory of Optoelectronic Materials and Technologies, Sun Yat-sen University, 510275, Guangzhou, China.

Nanoporous materials are widely explored as efficient adsorbents for the storage of gases and liquids as well as for effective low-dielectric materials in large-scale integrated circuits. These applications require fast heat transfer, while most nanoporous substances are thermal insulators. Here, the oriented growth of micrometer-sized single-crystal covalent organic frameworks (COFs) ribbons with nanoporous structures at an air-water interface is presented. The obtained COFs ribbons are interconnected into a continuous and purely crystalline thin film. Due to the robust connectivity among the COFs ribbons, the entire film can be easily transferred and reliably contacted with target supports. The measured thermal conductivity amounts to ∼5.31 ± 0.37 W m K at 305 K, which is so far the highest value for nanoporous materials. These findings provide a methodology to grow and assemble single-crystal COFs into large area ensembles for the exploration of functional properties and potentially lead to new devices with COFs thin films where both porosity and thermal conductivity are desired.
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http://dx.doi.org/10.1021/jacs.0c13458DOI Listing
March 2021

Exploring urine biomarkers of early health effects for occupational exposure to titanium dioxide nanoparticles using metabolomics.

Nanoscale 2021 Feb;13(7):4122-4132

Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing, 100191, People's Republic of China.

Many experimental studies have demonstrated that titanium dioxide nanoparticles (TiO2 NPs) could induce adverse health effects in vivo and in vitro. But epidemiological evidence and biomarkers related to early health effects are still lacking. This study aimed to explore biomarkers in the urine samples of workers occupationally exposed to a relatively low concentration of TiO2 NPs. A cross-sectional study was conducted in Jinan, China, involving 132 employees of a TiO2 NP manufacturing plant, among which the exposed group and control group were 1 : 1 matched by confounding factors such as gender, age, BMI, smoking and drinking. Untargeted metabolomics was performed in urine samples using high performance liquid chromatography-mass spectrometry (HPLC-MS) technology. The differential metabolites between the TiO2 NP exposed group and the control group were analyzed and then screened for potential biomarkers using bioinformatics methods. Metabolomics found a total of 1760 differentially expressed metabolites in the TiO2 NP exposed group, of which 60 differential metabolites were simultaneously confirmed by one-dimensional and multi-dimensional statistical analysis. Among these 60 differential metabolites, the relative expression of 27 metabolites increased, and the remaining 33 decreased. Pathway enrichment analysis further found that the metabolic pathway of long chain acyl-coa dehydrogenase deficiency (Lcad) was significantly enriched. Ten differential metabolites were selected as potential biomarkers of occupational exposure to TiO2 NPs using machine learning methods, including dibenzyl ether, quassimarin, tryptophan, etc. The receiver operating characteristic curves (ROCs) of these potential biomarkers showed good sensitivity and specificity. These potential biomarkers also had biological basis for occupational exposure to TiO2 NPs. Therefore, urine metabolites represented by dibenzyl ether are considered as good biomarkers of early health effects for occupational exposure to TiO2 NPs.
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http://dx.doi.org/10.1039/d0nr08792kDOI Listing
February 2021

Structural basis for ligand recognition of the neuropeptide Y Y receptor.

Nat Commun 2021 02 2;12(1):737. Epub 2021 Feb 2.

CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai, 201203, China.

The human neuropeptide Y (NPY) Y receptor (YR) plays essential roles in food intake, bone formation and mood regulation, and has been considered an important drug target for obesity and anxiety. However, development of drugs targeting YR remains challenging with no success in clinical application yet. Here, we report the crystal structure of YR bound to a selective antagonist JNJ-31020028 at 2.8 Å resolution. The structure reveals molecular details of the ligand-binding mode of YR. Combined with mutagenesis studies, the YR structure provides insights into key factors that define antagonistic activity of diverse antagonists. Comparison with the previously determined antagonist-bound YR structures identified receptor-ligand interactions that play different roles in modulating receptor activation and mediating ligand selectivity. These findings deepen our understanding about molecular mechanisms of ligand recognition and subtype specificity of NPY receptors, and would enable structure-based drug design.
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http://dx.doi.org/10.1038/s41467-021-21030-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854658PMC
February 2021

A Novel Transcriptome Integrated Network Approach Identifies the Key Driver lncRNA Involved in Cell Cycle With Chromium (VI)-Treated BEAS-2B Cells.

Front Genet 2020 13;11:597803. Epub 2021 Jan 13.

Department of Occupational and Environmental Health Science, School of Public Health, Peking University, Beijing, China.

Hexavalent chromium [Cr(VI)] is a well-known occupational carcinogen, but the mechanisms contributing to DNA damage and cell cycle alternation have not been fully characterized. To study the dose-response effects of Cr(VI) on transcription, we exposed BEAS-2B cells to Cr(VI) at concentrations of 0.2, 0.6, and 1.8 μmol/L for 24 h. Here, we identified 1,484 differentially expressed genes (DEGs) in our transcript profiling data, with the majority of differentially expressed transcripts being downregulated. Our results also showed that these DEGs were enriched in pathways associated with the cell cycle, including DNA replication, chromatin assembly, and DNA repair. Using the differential expressed genes related to cell cycle, a weighted gene co-expression network was constructed and a key mRNA-lncRNA regulation module was identified under a scale-free network with topological properties. Additionally, key driver analysis (KDA) was applied to the mRNA-lncRNA regulation module to identify the driver genes. The KDA revealed that ARD3 (FDR = 1.46 × 10), SND1 (FDR = 5.24 × 10), and lnc-DHX32-2:1 (FDR = 1.43 × 10) were particularly highlighted in the category of G2/M, G1/S, and M phases. Moreover, several genes we identified exhibited great connectivity in our causal gene network with every key driver gene, including CDK14, POLA1, lnc-NCS1-2:1, and lnc-FOXK1-4:1 (all FDR < 0.05 in those phases). Together, these results obtained using mathematical approaches and bioinformatics algorithmics might provide potential new mechanisms involved in the cytotoxicity induced by Cr.
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http://dx.doi.org/10.3389/fgene.2020.597803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838612PMC
January 2021

CHAOS Challenge - combined (CT-MR) healthy abdominal organ segmentation.

Med Image Anal 2021 04 25;69:101950. Epub 2020 Dec 25.

Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey. Electronic address:

Segmentation of abdominal organs has been a comprehensive, yet unresolved, research field for many years. In the last decade, intensive developments in deep learning (DL) introduced new state-of-the-art segmentation systems. Despite outperforming the overall accuracy of existing systems, the effects of DL model properties and parameters on the performance are hard to interpret. This makes comparative analysis a necessary tool towards interpretable studies and systems. Moreover, the performance of DL for emerging learning approaches such as cross-modality and multi-modal semantic segmentation tasks has been rarely discussed. In order to expand the knowledge on these topics, the CHAOS - Combined (CT-MR) Healthy Abdominal Organ Segmentation challenge was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI), 2019, in Venice, Italy. Abdominal organ segmentation from routine acquisitions plays an important role in several clinical applications, such as pre-surgical planning or morphological and volumetric follow-ups for various diseases. These applications require a certain level of performance on a diverse set of metrics such as maximum symmetric surface distance (MSSD) to determine surgical error-margin or overlap errors for tracking size and shape differences. Previous abdomen related challenges are mainly focused on tumor/lesion detection and/or classification with a single modality. Conversely, CHAOS provides both abdominal CT and MR data from healthy subjects for single and multiple abdominal organ segmentation. Five different but complementary tasks were designed to analyze the capabilities of participating approaches from multiple perspectives. The results were investigated thoroughly, compared with manual annotations and interactive methods. The analysis shows that the performance of DL models for single modality (CT / MR) can show reliable volumetric analysis performance (DICE: 0.98 ± 0.00 / 0.95 ± 0.01), but the best MSSD performance remains limited (21.89 ± 13.94 / 20.85 ± 10.63 mm). The performances of participating models decrease dramatically for cross-modality tasks both for the liver (DICE: 0.88 ± 0.15 MSSD: 36.33 ± 21.97 mm). Despite contrary examples on different applications, multi-tasking DL models designed to segment all organs are observed to perform worse compared to organ-specific ones (performance drop around 5%). Nevertheless, some of the successful models show better performance with their multi-organ versions. We conclude that the exploration of those pros and cons in both single vs multi-organ and cross-modality segmentations is poised to have an impact on further research for developing effective algorithms that would support real-world clinical applications. Finally, having more than 1500 participants and receiving more than 550 submissions, another important contribution of this study is the analysis on shortcomings of challenge organizations such as the effects of multiple submissions and peeking phenomenon.
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http://dx.doi.org/10.1016/j.media.2020.101950DOI Listing
April 2021

Risk Factors for Recurrent L4-5 Disc Herniation After Percutaneous Endoscopic Transforaminal Discectomy: A Retrospective Analysis of 654 Cases.

Risk Manag Healthc Policy 2020 18;13:3051-3065. Epub 2020 Dec 18.

Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qing'dao, Shandong Province 266000, People's Republic of China.

Background: Percutaneous endoscopic lumbar discectomy (PELD) is an increasingly applied minimally invasive procedure that has several advantages in the treatment of lumbar disc herniation (LDH). However, recurrent LDH (rLDH) has become a concerning postoperative complication. It remains difficult to establish a consensus and draw reliable conclusions regarding the risk factors for rLDH.

Purpose: This retrospective study aimed to investigate the risk factors associated with rLDH at the L4-5 level after percutaneous endoscopic transforaminal discectomy (PETD).

Methods: A total of 654 patients who underwent the PETD procedure at the L4-5 level from October 2013 to January 2020 were divided into a recurrence (R) group (n=46) and a nonrecurrence (N) group (n=608). Demographic and clinical data and imaging parameters were collected and analyzed using univariate and multiple regression analyses.

Results: The current study found a 7% rate of rLDH at the L4/5 level after successful PETD. Univariate analysis showed that older age, high BMI, diabetes mellitus history, smoking, large physical load intensity, moderate disc degeneration, small muscle-disc ratio (M/D), more fat infiltration, large sagittal range of motion (sROM), scoliosis, small disc height index (DHI), small intervertebral space angle (ISA), and small lumbar lordosis (LL) were potential risk factors (P < 0.10) for LDH recurrence after PETD at the L4-5 level. Multivariate analysis suggested that high BMI, large physical load intensity, moderate disc degeneration, small M/D, more fat infiltration, large sROM, small ISA, and small LL were independent significant risk factors for recurrence of LDH after PETD.

Conclusion: Consideration of disc degeneration, M/D, fat infiltration of the paravertebral muscles, sROM, ISA, LL, BMI, and physical load intensity prior to surgical intervention may contribute to the prevention of rLDH following PETD and lead to a more satisfactory operative outcome and the development of a reasonable rehabilitation program after discharge.
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http://dx.doi.org/10.2147/RMHP.S287976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755338PMC
December 2020

Adult mesenchymal stem cell ageing interplays with depressed mitochondrial Ndufs6.

Cell Death Dis 2020 12 15;11(12):1075. Epub 2020 Dec 15.

Guangzhou Women and Children's Medical Centre, Guangzhou Medical University, Guangzhou, Guangdong, China.

Mesenchymal stem cell (MSC)-based therapy has emerged as a novel strategy to treat many degenerative diseases. Accumulating evidence shows that the function of MSCs declines with age, thus limiting their regenerative capacity. Nonetheless, the underlying mechanisms that control MSC ageing are not well understood. We show that compared with bone marrow-MSCs (BM-MSCs) isolated from young and aged samples, NADH dehydrogenase (ubiquinone) iron-sulfur protein 6 (Ndufs6) is depressed in aged MSCs. Similar to that of Ndufs6 knockout (Ndufs6) mice, MSCs exhibited a reduced self-renewal and differentiation capacity with a tendency to senescence in the presence of an increased p53/p21 level. Downregulation of Ndufs6 by siRNA also accelerated progression of wild-type BM-MSCs to an aged state. In contrast, replenishment of Ndufs6 in Ndufs6-BM-MSCs significantly rejuvenated senescent cells and restored their proliferative ability. Compared with BM-MSCs, Ndufs6-BM-MSCs displayed increased intracellular and mitochondrial reactive oxygen species (ROS), and decreased mitochondrial membrane potential. Treatment of Ndufs6-BM-MSCs with mitochondrial ROS inhibitor Mito-TEMPO notably reversed the cellular senescence and reduced the increased p53/p21 level. We provide direct evidence that impairment of mitochondrial Ndufs6 is a putative accelerator of adult stem cell ageing that is associated with excessive ROS accumulation and upregulation of p53/p21. It also indicates that manipulation of mitochondrial function is critical and can effectively protect adult stem cells against senescence.
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http://dx.doi.org/10.1038/s41419-020-03289-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738680PMC
December 2020

A truncated intracellular Dicer-like molecule involves in antiviral immune recognition of oyster Crassostrea gigas.

Dev Comp Immunol 2021 Mar 18;116:103931. Epub 2020 Nov 18.

Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China; Southern Laboratory of Ocean Science and Engineering (Guangdong,Zhuhai), Zhuhai, 519000, China; Laboratory of Marine Fisheries Science and Food Production Process, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266235, China; Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, 116023, China. Electronic address:

The enzyme Dicer is best known for its role as an endoribonuclease in the small RNA pathway, playing a crucial role in recognizing viral double-stranded RNA (dsRNA) and inducing down-stream cascades to mediate anti-virus immunity. In the present study, a truncated Dicer-like gene was identified from oyster Crassostrea gigas, and its open reading frame (ORF) encoded a polypeptide (designed as CgDCL) of 530 amino acids. The CgDCL contained one N-terminal DEAD domain and a C-terminal helicase domain, but lack the conserved PAZ domain, ribonuclease domain (RIBOc) and dsRNA binding domain. The mRNA transcripts of CgDCL were detected in all the examined tissues with high expression levels in lip, gills and haemocytes, which were 62.06-fold, 48.91-fold and 47.13-fold (p < 0.05) of that in mantle, respectively. In the primarily cultured oyster haemocytes, the mRNA transcripts of CgDCL were significantly induced at 12 h after poly(I:C) stimulation, which were 4.04-fold (p < 0.05) of that in control group. The expression level of CgDCL mRNA in haemocytes was up-regulated significantly after dsRNA and recombinant interferon-like protein (rCgIFNLP) injection, which was 12.87-fold (p < 0.01) and 3.22-fold (p < 0.05) of that in control group, respectively. CgDCL proteins were mainly distributed in the cytoplasm of haemocytes. The recombinant CgDCL protein displayed binding activity to dsRNA and poly(I:C), but no obvious dsRNA cleavage activity. These results collectively suggest that truncated CgDCL from C. gigas was able to be activated by poly(I:C), dsRNA and CgIFNLP, and functioned as an intracellular recognition molecule to bind nucleic acid of virus, indicating a potential mutual cooperation between RNAi and IFN-like system in anti-virus immunity of oysters.
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http://dx.doi.org/10.1016/j.dci.2020.103931DOI Listing
March 2021

Bta-miR-223 Targeting CBLB Contributes to Resistance to Mastitis Through the PI3K/AKT/NF-κB Pathway.

Front Vet Sci 2020 21;7:529. Epub 2020 Aug 21.

College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China.

Bovine mastitis is an inflammatory condition of the mammary gland often caused by () infection. The aim of this study was to identify mastitis-related miRNAs and their downstream target genes, and therefore elucidate the regulatory mechanisms involved in disease progression and resistance. Three healthy and three mastitic cows were identified on the basis of the somatic cell count and bacterial culture of their milk, and the histological examination of udder tissues. High-throughput RNA sequencing and bioinformatic analyses revealed that 48 differentially expressed miRNAs (DEMs) in the mastitic udder tissues relative to the healthy tissues. Among 48 DEMs, the expression level of bta-miR-223 was the most up-regulated. Overexpression of the bta-miR-223 in Mac-T cells mitigated the inflammatory pathways induced by -derived lipoteichoic acid (LTA). The Cbl proto-oncogene B (CBLB) was identified as the target gene of bta-miR-223, and the direct binding of the miRNA to the CBLB promoter was confirmed by dual luciferase reporter assay using wild-type and mutant 3'-UTR constructs. Furthermore, overexpression of in the LTA-stimulated Mac-T cells significantly upregulated PI3K, AKT, and phosphorylated NF-κB p65, whereas knockdown had the opposite effect. Consistent with the findings, the mammary glands of mice infected with 10CFU/100 μL showed high levels of CBLB, PI3K, AKT, and p-NF-κB p65 48 h after infection. Taken together, bta-miR-223 is a predominant miRNA involved in mastitis, and bta-miR-223 likely mitigates the inflammatory progression by targeting CBLB and inhibiting the downstream PI3K/AKT/NF-κB pathway.
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http://dx.doi.org/10.3389/fvets.2020.00529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475710PMC
August 2020

Hedgehog pathway activation through nanobody-mediated conformational blockade of the Patched sterol conduit.

Proc Natl Acad Sci U S A 2020 11 2;117(46):28838-28846. Epub 2020 Nov 2.

Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;

Activation of the Hedgehog pathway may have therapeutic value for improved bone healing, taste receptor cell regeneration, and alleviation of colitis or other conditions. Systemic pathway activation, however, may be detrimental, and agents amenable to tissue targeting for therapeutic application have been lacking. We have developed an agonist, a conformation-specific nanobody against the Hedgehog receptor Patched1 (PTCH1). This nanobody potently activates the Hedgehog pathway in vitro and in vivo by stabilizing an alternative conformation of a Patched1 "switch helix," as revealed by our cryogenic electron microscopy structure. Nanobody-binding likely traps Patched in one stage of its transport cycle, thus preventing substrate movement through the Patched1 sterol conduit. Unlike the native Hedgehog ligand, this nanobody does not require lipid modifications for its activity, facilitating mechanistic studies of Hedgehog pathway activation and the engineering of pathway activating agents for therapeutic use. Our conformation-selective nanobody approach may be generally applicable to the study of other PTCH1 homologs.
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http://dx.doi.org/10.1073/pnas.2011560117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682405PMC
November 2020

FOXO1 promotes tumor progression by increased M2 macrophage infiltration in esophageal squamous cell carcinoma.

Theranostics 2020 16;10(25):11535-11548. Epub 2020 Sep 16.

Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

The transcription factor forkhead box protein O1 (FOXO1) is critical for regulating cytokine and chemokine secretion. However, its function in the tumor microenvironment (TME) remains largely unexplored. In this study, we characterized the prognostic value of FOXO1 and the interaction between tumor-derived FOXO1 and M2 macrophages in esophageal squamous cell carcinoma (ESCC). FOXO1 expression and macrophage infiltration in clinical samples and mouse models were quantified using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry staining. Western blotting, qRT-PCR, and enzyme-linked immunosorbent assay were used to evaluate chemokine ligand 20 (CCL20) and colony stimulating factor 1 (CSF-1) expression in FOXO1(+) and FOXO1(-) tumor cells. Macrophage phenotypes were determined using qRT-PCR, flow cytometry, and RNA sequencing. Transcriptional activity was measured using chromatin immunoprecipitation (ChIP)-qPCR. Tumor viability was investigated using XTT proliferation and foci formation assays. FOXO1 upregulation in tumor tissues was found to drive the polarization of M0 macrophages and infiltration of M2 macrophages into the TME, resulting in worse prognosis in ESCC patients. CSF-1, a vital factor inducing M0-to-M2 polarization, was upregulated via a FOXO1-mediated mechanism. RNA sequencing results corroborated that the FOXO1-induced macrophages exhibited similar molecular signatures to the IL4-stimulated M2 macrophages. The transwell assays showed that FOXO1 promoted the migration of M2 macrophages via CCL20 secretion, which could be inhibited using an anti-CCL20 antibody. FOXO1(+) tumor-induced M2 macrophages promoted tumor proliferation via the FAK-PI3K-AKT pathway and the PI3K inhibitor could effectively impede the oncogenical process. FOXO1 facilitated M0-to-M2 polarization and the recruitment of M2 macrophages in the TME via the transcriptional modulation of CCL20 and CSF-1. Our data deciphered the FOXO1-dependent mechanism in M2 macrophage infiltration in the TME of ESCC, which has implications for the development of novel prognostic and therapeutic targets to optimize the current treatment against ESCC.
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http://dx.doi.org/10.7150/thno.45261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546008PMC
June 2021

Tissue-specific oxidative stress and element distribution after oral exposure to titanium dioxide nanoparticles in rats.

Nanoscale 2020 Oct;12(38):20033-20046

Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, China.

Dietary and environmental exposure to titanium dioxide nanoparticles (TiO2 NPs) can cause low-dose and long-term oral exposure in the population, posing a potential adverse health risk. Oxidative stress is considered to be the primary effect of TiO2 NPs through biological interaction. In the present study, we conducted an animal experiment to investigate the element distribution and oxidative stress in Sprague-Dawley rats after oral exposure to TiO2 NPs at daily doses of 0, 2, 10, and 50 mg kg-1 for 90 days. Through the detection of Ti element content in various tissues, limited absorption and distribution of TiO2 NPs in rats was found. However, orally ingested TiO2 NPs still induced tissue-specific oxidative stress and imbalance of elements. Liver tissue was the most sensitive tissue to TiO2 NP-induced oxidative stress, showing decreased reduced glutathione (GSH), increased oxidized glutathione (GSSG) and decreased ratio of GSH/GSSG as well as accumulation of lipid peroxidation (malondialdehyde, MDA) in liver tissues of rats after TiO2 NP exposure (10 and 50 mg kg-1). Meanwhile, oral exposure to TiO2 NPs caused a significant reduction in metal elements such as Mg, Ca and Co in various tissues. Through bioinformatics analysis, the tissue specificity and correlation between the imbalance of elements and oxidative stress were statistically confirmed, but it was difficult to understand the causal relationship. Disorder of element distribution and oxidative stress may lead to a series of subsequent adverse health effects and the tissue specificity would partly explain the target effects of TiO2 NPs.
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http://dx.doi.org/10.1039/d0nr05591cDOI Listing
October 2020

Analysis of the atomic structure of CdS magic-size clusters by X-ray absorption spectroscopy.

Nanoscale 2020 Oct;12(37):19325-19332

Centre of Condensed Matter and Materials Physics, Queen Mary University of London, Mile End Road, E1 4NS, London, UK.

Magic-size clusters are ultra-small colloidal semiconductor systems that are intensively studied due to their monodisperse nature and sharp UV-vis absorption peak compared with regular quantum dots. However, the small size of such clusters (<2 nm), and the large surface-to-bulk ratio significantly limit characterisation techniques that can be utilised. Here we demonstrate how a combination of EXAFS and XANES analyses can be used to obtain information about sample stoichiometry and cluster symmetry. Investigating two types of clusters that show sharp UV-vis absorption peaks at 311 nm and 322 nm, we found that both samples possess approximately 2 : 1 Cd : S ratio and have similar nearest-neighbour structural arrangements. However, both samples demonstrate a significant departure from the tetrahedral structural arrangement, with an average bond angle determined to be around 106.1° showing a bi-fold bond angle distribution. Our results suggest that both samples are quasi-isomers - their core structures have identical chemical compositions, but different atomic arrangements with distinct bond angle distributions.
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http://dx.doi.org/10.1039/d0nr05186aDOI Listing
October 2020

[Effect of subacute combined oral exposure of titanium dioxide nanoparticles and glucose on blood glucose homeostasis in young SD rats].

Wei Sheng Yan Jiu 2020 Jul;49(4):527-533

Department of Occupational and Enviromental Health Sciences, School of Public Health, Peking University Health Science Center, Beijing 100191, China.

Objective: To explore the effect of combined oral exposure of titanium dioxide nanoparticles(TiO_2 NPs) and glucose on blood glucose homeostasis in young SD rats.

Methods: Eighty 4-week-old young SD rats were randomly divided into 8 groups(10 rats in each group, half male and half female). The rats were exposed to TiO_2 NPs through intragastric administration at 0, 2, 10 and 50 mg/kg with or without 1. 8 g/kg glucose daily for 30 days. Blood glucose was monitored weekly during the experiment. Oral glucose tolerance test(OGTT) was carried out after subacute exposure(30 days), and the biomarkers related to blood glucose homeostasis were detected, including the contents of glycosylated serum protein(GSP), glycosylated hemoglobin(HbA1 c), insulin, C-peptide and glucagon. At the same time, the pancreatic pathology of rats was observed.

Results: TiO_2 NPs were anatase crystals, closely spherical shape, with an average particle size of(24±5)nm. Exposure of TiO_2 NPs alone had little effect on blood glucose homeostasis. Blood glucose decreased on the 16 th exposure day at dose of 10 mg/kg TiO_2 NPs, and postprandial blood glucose(2 h) decreased after 30 days of TiO_2 NPs exposure at doses of 2 and 50 mg/kg in male rats(P<0. 05). The combined effect of oral exposure of TiO_2 NPs and glucose on blood glucose homeostasis was more obvious than that of TiO_2 NPs alone. Blood glucose decreased on the 9 th exposure day at dose of 10 mg/kg TiO_2 NPs+glucose in female rats, and postprandial blood glucose(2 h) decreased at dose of 2 and 50 mg/kg TiO_2 NPs+glucose after 30 days of exposure in male rats(P<0. 05). Blood glucose decreased on the 9 th day after 10 mg/kg TiO_2 NPs+glucose exposure in female rats. The glycosylated serum protein decreased and postprandial blood glucose(30 and 60 min) as well as the area under curve of OGTT increased in male rats after 30 days of exposure(P<0. 05). The changes of blood glucose-regulating hormones were only found after the combined exposure of 10 mg/kg TiO_2 NPs+glucose for 30 days, including the decrease of insulin in female rats, as well as the decrease of insulin and the increase of glucagon in male rats(P<0. 05). The interaction analysis showed that TiO_2 NPs and glucose had significant synergistic effect on postprandial blood glucose(60 min) in male rats(P<0. 05). No abnormality was found in the pathological observation of pancreas in rats of experimental groups.

Conclusion: Subacute combined oral exposure of TiO_2 NPs and glucose could affect the blood glucose homeostasis of young SD rats, resultsing in temporary hypoglycemia and impaired glucose tolerance, as well as adaptive changes of blood glucose-regulating hormones. The male rats were more sensitive. Compared with the exposure of TiO_2 NPs alone, the combined exposure of TiO_2 NPs and glucose induced more significant effects. Significant synergistic effect between them occurred on postprandial blood glucose.
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http://dx.doi.org/10.19813/j.cnki.weishengyanjiu.2020.04.001DOI Listing
July 2020

Longitudinal Multi-omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome.

Cell 2020 09 10;182(6):1460-1473.e17. Epub 2020 Sep 10.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA. Electronic address:

The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease has been difficult due to apparent disconnects between animal and human studies and lack of an integrated multi-omics view of disease-specific physiological changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome, and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtype-specific and symptom-related variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases. VIDEO ABSTRACT.
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http://dx.doi.org/10.1016/j.cell.2020.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109273PMC
September 2020

RNA-protein interaction mapping via MS2- or Cas13-based APEX targeting.

Proc Natl Acad Sci U S A 2020 09 24;117(36):22068-22079. Epub 2020 Aug 24.

Department of Genetics, Chan Zuckerberg Biohub, Stanford University, Stanford, CA 94305;

RNA-protein interactions underlie a wide range of cellular processes. Improved methods are needed to systematically map RNA-protein interactions in living cells in an unbiased manner. We used two approaches to target the engineered peroxidase APEX2 to specific cellular RNAs for RNA-centered proximity biotinylation of protein interaction partners. Both an MS2-MCP system and an engineered CRISPR-Cas13 system were used to deliver APEX2 to the human telomerase RNA hTR with high specificity. One-minute proximity biotinylation captured candidate binding partners for hTR, including more than a dozen proteins not previously linked to hTR. We validated the interaction between hTR and the -methyladenosine (mA) demethylase ALKBH5 and showed that ALKBH5 is able to erase the mA modification on endogenous hTR. ALKBH5 also modulates telomerase complex assembly and activity. MS2- and Cas13-targeted APEX2 may facilitate the discovery of novel RNA-protein interactions in living cells.
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http://dx.doi.org/10.1073/pnas.2006617117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486720PMC
September 2020

PSCs Reveal PUFA-Provoked Mitochondrial Stress as a Central Node Potentiating RPE Degeneration in Bietti's Crystalline Dystrophy.

Mol Ther 2020 12 25;28(12):2642-2661. Epub 2020 Jul 25.

Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Prenatal Diagnostic Centre and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China; State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China. Electronic address:

Bietti's crystalline dystrophy (BCD) is an incurable retinal disorder caused by the polypeptide 2 of cytochrome P450 family 4 subfamily V (CYP4V2) mutations. Patients with BCD present degeneration of retinal pigmented epithelial (RPE) cells and consequent blindness. The lack of appropriate disease models and patients' RPE cells limits our understanding of the pathological mechanism of RPE degeneration. In this study, using CYP4V2 mutant pluripotent stem cells as disease models, we demonstrated that RPE cells with CYP4V2 mutations presented a disrupted fatty acid homeostasis, which were characterized with excessive accumulation of poly-unsaturated fatty acid (PUFA), including arachidonic acid (AA) and eicosapentaenoic acid (EPA). The PUFA overload increased mitochondrial reactive oxygen species, impaired mitochondrial respiratory functions, and triggered mitochondrial stress-activated p53-independent apoptosis in CYP4V2 mutant RPE cells. Restoration of the mutant CYP4V2 using adeno-associated virus 2 (AAV2) can effectively reduce PUFA deposition, alleviate mitochondria oxidative stresses, and rescue RPE cell death in BCD RPE cells. Taken together, our results highlight a role of PUFA-induced mitochondrial damage as a central node to potentiate RPE degeneration in BCD patients. AAV2-mediated gene therapy may represent a feasible strategy for the treatment of BCD.
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http://dx.doi.org/10.1016/j.ymthe.2020.07.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704739PMC
December 2020

SARS-CoV-2 infects human neural progenitor cells and brain organoids.

Cell Res 2020 10 4;30(10):928-931. Epub 2020 Aug 4.

School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 3/F, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong, China.

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http://dx.doi.org/10.1038/s41422-020-0390-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399356PMC
October 2020

Skipping breakfast and physical fitness among school-aged adolescents.

Clinics (Sao Paulo) 2020 22;75:e1599. Epub 2020 Jul 22.

Department of Epidemiology, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China.

Objectives: This study explored the relationship between skipping breakfast and physical fitness in a group of school-aged adolescents in China.

Methods: This cross-sectional study from the Chinese National Surveillance on Students' Constitution and Health (CNSSCH) survey in Ningbo, China, used a standardized questionnaire to assess the frequency of breakfast consumption. Physical fitness was measured through standing long jump, 50-m sprint, 1,000 (or 800)-m run, and vital capacity tests. Multiple linear regression analysis was used to investigate the relationship between the frequency of breakfast consumption and physical fitness.

Results: Our study included a total of 1,849 school-aged adolescents (aged 15.53±1.80 years). Among boys, non-breakfast-skippers had good scores for 50-m sprints, 1,000-m run, and vital capacity tests when compared with breakfast skippers (all p<0.05). Among girls, non-breakfast-skippers had a good scores for the standing long jump test compared with breakfast skippers (p=0.003). The multiple linear regression model showed that not skipping breakfast was positively associated with vital capacity (β=-173.78, p=0.004) and inversely associated with 50-m sprint (β=-0.12, p=0.018) and 1,000-m run times (β=-8.08, p=0.001) in boys.

Conclusion: The results of this cross-sectional study revealed that skipping breakfast might be associated with lower physical fitness in Chinese adolescents aged 13-18 years, especially boys. Breakfast consumption should be promoted among Chinese school-aged boys.
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http://dx.doi.org/10.6061/clinics/2020/e1599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362721PMC
November 2020

Recovery of pneumonia in 27 discharged COVID-19 patients with positive virus detection.

Quant Imaging Med Surg 2020 Jul;10(7):1572-1575

Department of Epidemiology, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, Guangzhou, China.

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http://dx.doi.org/10.21037/qims-20-656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358416PMC
July 2020

Longitudinal analysis of regional cerebellum volumes during normal aging.

Neuroimage 2020 10 25;220:117062. Epub 2020 Jun 25.

Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, 20892, USA.

Some cross-sectional studies suggest reduced cerebellar volumes with aging, but there have been few longitudinal studies of age changes in cerebellar subregions in cognitively healthy older adults. In this work, 2,023 magnetic resonance (MR) images of 822 cognitively normal participants from the Baltimore Longitudinal Study of Aging (BLSA) were analyzed. Participants ranged in age from 50 to 95 years (mean 70.7 years) at the baseline assessment. Follow-up intervals were 1-9 years (mean 3.7 years) for participants with two or more visits. We used a recently developed cerebellum parcellation algorithm based on convolutional neural networks to divide the cerebellum into 28 subregions. Linear mixed effects models were applied to the volume of each cerebellar subregion to investigate cross-sectional and longitudinal age effects, as well as effects of sex and their interactions, after adjusting for intracranial volume. Our findings suggest spatially varying atrophy patterns across the cerebellum with respect to age and sex both cross-sectionally and longitudinally.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117062DOI Listing
October 2020