Publications by authors named "Hong Qin"

268 Publications

Fisetin inhibits inflammation and induces autophagy by mediating PI3K/AKT/mTOR signaling in LPS-induced RAW264.7 cells.

Food Nutr Res 2021 25;65. Epub 2021 Mar 25.

Xiangya School of Public Health, Central South University, Changsha, China.

Background: Fisetin, a natural potent flavonoid, has various beneficial, pharmacological activities. In this study, we investigated expression changes of the fisetin regulating genes in lipopolysaccharide (LPS)-treated RAW264.7 cells and explored the role of fisetin in inflammation and autophagy.

Methods And Results: Microarray analysis identified 1,071 genes that were regulated by fisetin in LPS-treated RAW264.7 cells, and these genes were mainly related to the process of immune system response. Quantitative real-time polymerase chain reaction and Bio-Plex analysis indicated that fisetin decreased the expression and secretion of several inflammatory cytokines in cells administered with LPS. Western blot analysis and immunofluorescence assay showed that fisetin decreased microtubule-associated protein 1 light-chain 3B (LC3B) and lysosome-associated membrane protein 1 (LAMP1) expression in LPS-treated cells, while the autophagy inhibitor chloroquine (CQ) could partially reverse this effect. In addition, fisetin reduced the elevated expression of p-PI3K, p-AKT and p-mTOR induced by LPS in a concentration-dependent manner.

Conclusions: Fisetin diminished the expression and secretion of inflammatory cytokines and facilitated autophagosome-lysosome fusion and degradation in LPS-treated RAW264.7 cells via inhibition of the PI3K/AKT/mTOR signaling pathway. Overall, the results of this study provide new clues for the anti-inflammatory mechanism of fisetin and explain the crosstalk between autophagy and inflammation to some extent.
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http://dx.doi.org/10.29219/fnr.v65.6355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009086PMC
March 2021

Rethinking Image Salient Object Detection: Object-Level Semantic Saliency Reranking First, Pixelwise Saliency Refinement Later.

IEEE Trans Image Process 2021 12;30:4238-4252. Epub 2021 Apr 12.

Human attention is an interactive activity between our visual system and our brain, using both low-level visual stimulus and high-level semantic information. Previous image salient object detection (SOD) studies conduct their saliency predictions via a multitask methodology in which pixelwise saliency regression and segmentation-like saliency refinement are conducted simultaneously. However, this multitask methodology has one critical limitation: the semantic information embedded in feature backbones might be degenerated during the training process. Our visual attention is determined mainly by semantic information, which is evidenced by our tendency to pay more attention to semantically salient regions even if these regions are not the most perceptually salient at first glance. This fact clearly contradicts the widely used multitask methodology mentioned above. To address this issue, this paper divides the SOD problem into two sequential steps. First, we devise a lightweight, weakly supervised deep network to coarsely locate the semantically salient regions. Next, as a postprocessing refinement, we selectively fuse multiple off-the-shelf deep models on the semantically salient regions identified by the previous step to formulate a pixelwise saliency map. Compared with the state-of-the-art (SOTA) models that focus on learning the pixelwise saliency in single images using only perceptual clues, our method aims at investigating the object-level semantic ranks between multiple images, of which the methodology is more consistent with the human attention mechanism. Our method is simple yet effective, and it is the first attempt to consider salient object detection as mainly an object-level semantic reranking problem.
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http://dx.doi.org/10.1109/TIP.2021.3068649DOI Listing
April 2021

Overexpression of an Phosphopyruvate Carboxylase Improves Plant Growth and Stress Tolerance.

Cells 2021 Mar 6;10(3). Epub 2021 Mar 6.

Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA.

It has been challenging to simultaneously improve photosynthesis and stress tolerance in plants. Crassulacean acid metabolism (CAM) is a CO-concentrating mechanism that facilitates plant adaptation to water-limited environments. We hypothesized that the ectopic expression of a CAM-specific phosphopyruvate carboxylase (PEPC), an enzyme that catalyzes primary CO fixation in CAM plants, would enhance both photosynthesis and abiotic stress tolerance. To test this hypothesis, we engineered a CAM-specific gene (named ) from into tobacco. In comparison with wild-type and empty vector controls, transgenic tobacco plants constitutively expressing showed a higher photosynthetic rate and biomass production under normal conditions, along with significant carbon metabolism changes in malate accumulation, the carbon isotope ratio δC, and the expression of multiple orthologs of CAM-related genes. Furthermore, overexpression enhanced proline biosynthesis, and improved salt and drought tolerance in the transgenic plants. Under salt and drought stress conditions, the dry weight of transgenic tobacco plants overexpressing was increased by up to 81.8% and 37.2%, respectively, in comparison with wild-type plants. Our findings open a new door to the simultaneous improvement of photosynthesis and stress tolerance in plants.
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http://dx.doi.org/10.3390/cells10030582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999111PMC
March 2021

Protein interaction potential landscapes for yeast replicative aging.

Sci Rep 2021 Mar 30;11(1):7143. Epub 2021 Mar 30.

Department of Computer Science and Engineering, The University of Tennessee at Chattanooga, Chattanooga, TN, 37405, USA.

We proposed a novel interaction potential landscape approach to map the systems-level profile changes of gene networks during replicative aging in Saccharomyces cerevisiae. This approach enabled us to apply quasi-potentials, the negative logarithm of the probabilities, to calibrate the elevation of the interaction landscapes with young cells as a reference state. Our approach detected opposite landscape changes based on protein abundances from transcript levels, especially for intra-essential gene interactions. We showed that essential proteins play different roles from hub proteins on the age-dependent interaction potential landscapes. We verified that hub proteins tend to avoid other hub proteins, but essential proteins prefer to interact with other essential proteins. Overall, we showed that the interaction potential landscape is promising for inferring network profile change during aging and that the essential hub proteins may play an important role in the uncoupling between protein and transcript levels during replicative aging.
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http://dx.doi.org/10.1038/s41598-021-86415-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010020PMC
March 2021

Exploring Rich and Efficient Spatial Temporal Interactions for Real-Time Video Salient Object Detection.

IEEE Trans Image Process 2021 5;30:3995-4007. Epub 2021 Apr 5.

We have witnessed a growing interest in video salient object detection (VSOD) techniques in today's computer vision applications. In contrast with temporal information (which is still considered a rather unstable source thus far), the spatial information is more stable and ubiquitous, thus it could influence our vision system more. As a result, the current main-stream VSOD approaches have inferred and obtained their saliency primarily from the spatial perspective, still treating temporal information as subordinate. Although the aforementioned methodology of focusing on the spatial aspect is effective in achieving a numeric performance gain, it still has two critical limitations. First, to ensure the dominance by the spatial information, its temporal counterpart remains inadequately used, though in some complex video scenes, the temporal information may represent the only reliable data source, which is critical to derive the correct VSOD. Second, both spatial and temporal saliency cues are often computed independently in advance and then integrated later on, while the interactions between them are omitted completely, resulting in saliency cues with limited quality. To combat these challenges, this paper advocates a novel spatiotemporal network, where the key innovation is the design of its temporal unit. Compared with other existing competitors (e.g., convLSTM), the proposed temporal unit exhibits an extremely lightweight design that does not degrade its strong ability to sense temporal information. Furthermore, it fully enables the computation of temporal saliency cues that interact with their spatial counterparts, ultimately boosting the overall VSOD performance and realizing its full potential towards mutual performance improvement for each. The proposed method is easy to implement yet still effective, achieving high-quality VSOD at 50 FPS in real-time applications.
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http://dx.doi.org/10.1109/TIP.2021.3068644DOI Listing
April 2021

The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis.

Cell Death Dis 2021 Mar 26;12(4):328. Epub 2021 Mar 26.

Centre for Lipid Research and Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, 400016, Chongqing, China.

Metabolic reprogramming is a new hallmark of cancer but it remains poorly defined in hepatocellular carcinogenesis (HCC). The fatty acid receptor CD36 is associated with both lipid and glucose metabolism in the liver. However, the role of CD36 in metabolic reprogramming in the progression of HCC still remains to be elucidated. In the present study, we found that CD36 is highly expressed in human HCC as compared with non-tumor hepatic tissue. CD36 overexpression promoted the proliferation, migration, invasion, and in vivo tumor growth of HCC cells, whereas silencing CD36 had the opposite effects. By analysis of cell metabolic phenotype, CD36 expression showed a positive association with extracellular acidification rate, a measure of glycolysis, instead of oxygen consumption rate. Further experiments verified that overexpression of CD36 resulted in increased glycolysis flux and lactic acid production. Mechanistically, CD36 induced mTOR-mediated oncogenic glycolysis via activation of Src/PI3K/AKT signaling axis. Pretreatment of HCC cells with PI3K/AKT/mTOR inhibitors largely blocked the tumor-promoting effect of CD36. Our findings suggest that CD36 exerts a stimulatory effect on HCC growth and metastasis, through mediating aerobic glycolysis by the Src/PI3K/AKT/mTOR signaling pathway.
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http://dx.doi.org/10.1038/s41419-021-03596-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997878PMC
March 2021

Lipid Metabolism and Tumor Antigen Presentation.

Authors:
Hong Qin Yaxi Chen

Adv Exp Med Biol 2021 ;1316:169-189

Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Institute for Viral Hepatitis, Centre for Lipid Research, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

Tumors always evade immune surveillance and block T cell activation in a poorly immunogenic and immunosuppressive environment. Cancer cells and immune cells exhibit metabolic reprogramming in the tumor microenvironment (TME), which intimately links immune cell function and edits tumor immunology. In addition to glucose metabolism, amino acid and lipid metabolism also provide the materials for biological processes crucial in cancer biology and pathology. Furthermore, lipid metabolism is synergistically or negatively involved in the interactions between tumors and the microenvironment and contributes to the regulation of immune cells. Antigen processing and presentation as the initiation of adaptive immune response play a critical role in antitumor immunity. Therefore, a relationship exists between antigen-presenting cells and lipid metabolism in TME. This chapter introduces the updated understandings of lipid metabolism of tumor antigen-presenting cells and describes new directions in the manipulation of immune responses for cancer treatment.
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http://dx.doi.org/10.1007/978-981-33-6785-2_11DOI Listing
March 2021

Complementary performances of convolutional and capsule neural networks on classifying microfluidic images of dividing yeast cells.

PLoS One 2021 17;16(3):e0246988. Epub 2021 Mar 17.

SimCenter, Department of Computer Science and Engineering, University of Tennessee at Chattanooga, Chattanooga, Tennessee, United States of America.

Microfluidic-based assays have become effective high-throughput approaches to examining replicative aging of budding yeast cells. Deep learning may offer an efficient way to analyze a large number of images collected from microfluidic experiments. Here, we compare three deep learning architectures to classify microfluidic time-lapse images of dividing yeast cells into categories that represent different stages in the yeast replicative aging process. We found that convolutional neural networks outperformed capsule networks in terms of accuracy, precision, and recall. The capsule networks had the most robust performance in detecting one specific category of cell images. An ensemble of three best-fitted single-architecture models achieves the highest overall accuracy, precision, and recall due to complementary performances. In addition, extending classification classes and data augmentation of the training dataset can improve the predictions of the biological categories in our study. This work lays a useful framework for sophisticated deep-learning processing of microfluidic-based assays of yeast replicative aging.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246988PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968698PMC
March 2021

Biotin exposure-based immunomagnetic separation coupled with sodium dodecyl sulfate, propidium monoazide, and multiplex real-time PCR for rapid detection of viable Salmonella Typhimurium, Staphylococcus aureus, and Listeria monocytogenes in milk.

J Dairy Sci 2021 Mar 10. Epub 2021 Mar 10.

Xiangya School of Public Health, Central South University, Changsha 410078, P. R. China. Electronic address:

In this study, we established a rapid and sensitive method for the detection of viable Salmonella Typhimurium, Staphylococcus aureus, and Listeria monocytogenes in milk using biotin-exposure-based immunomagnetic separation (IMS) combined with sodium dodecyl sulfate (SDS), propidium monoazide (PMA), and multiplex real-time PCR (mRT-PCR). We used IMS to lessen the assay time for isolation of target bacteria. We then optimized the coupling conditions and immunomagnetic capture process. The immunoreaction and incubation times for 5 μg of mAb coupled with 500 μg of streptavidin-functionalized magnetic beads using a streptavidin-biotin system were 90 and 30 min, respectively. Treatment with SDS-PMA before mRT-PCR amplification eliminated false-positive outcomes from dead bacteria and identified viable target bacteria with good sensitivity and specificity. The limit of detection of IMS combined with the SDS-PMA-mRT-PCR assay for the detection of viable Salmonella Typhimurium, Staph. aureus, and L. monocytogenes in spiked milk matrix samples was 10 cfu/mL and remained significant even in the appearance of 10 cfu/mL of nontarget bacteria. The entire detection process was able to identify viable bacteria within 9 h. The combination of biotin-exposure-mediated IMS and SDS-PMA-mRT-PCR has potential value for the rapid and sensitive detection of foodborne pathogens.
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http://dx.doi.org/10.3168/jds.2020-19887DOI Listing
March 2021

Neutron total scattering investigation on the dissolution mechanism of trehalose in NaOH/urea aqueous solution.

Struct Dyn 2021 Jan 10;8(1):014901. Epub 2021 Feb 10.

Institute for Advanced Study, Shenzhen University, Shenzhen 508060, China.

Trehalose is chosen as a model molecule to investigate the dissolution mechanism of cellulose in NaOH/urea aqueous solution. The combination of neutron total scattering and empirical potential structure refinement yields the most probable all-atom positions in the complex fluid and reveals the cooperative dynamic effects of NaOH, urea, and water molecules in the dissolution process. NaOH directly interacts with glucose rings by breaking the inter- and intra-molecular hydrogen bonding. Na, thus, accumulates around electronegative oxygen atoms in the hydration shell of trehalose. Its local concentration is thereby 2-9 times higher than that in the bulk fluid. Urea molecules are too large to interpenetrate into trehalose and too complex to form hydrogen bonds with trehalose. They can only participate in the formation of the hydration shell around trehalose via Na bridging. As the main component in the complex fluid, water molecules have a disturbed tetrahedral structure in the presence of NaOH and urea. The structure of the mixed solvent does not change when it is cooled to -12 °C. This indicates that the dissolution may be a dynamic process, i.e., a competition between hydration shell formation and inter-molecule hydrogen bonding determines its dissolution. We, therefore, predict that alkali with smaller ions, such as LiOH, has better solubility for cellulose.
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http://dx.doi.org/10.1063/4.0000065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889297PMC
January 2021

Objective visual quality one year after toric IOL implantation for correction of moderate and high corneal astigmatism.

Int J Ophthalmol 2021 18;14(2):245-249. Epub 2021 Feb 18.

Eye Hospital of China Academy of Chinese Medical Sciences, Beijing 100040, China.

Aim: To compare the objective visual quality after implantation of a toric intraocular lens (IOL) in order to correct moderate or high corneal astigmatism at the one year postoperative follow-up.

Methods: From December 2017 to June 2018, 66 patients (90 eyes) with simple age-related cataract with regular corneal astigmatism greater than 1.5 D were enrolled in this prospective self-control study. The patients were implanted with Proming toric IOL (model: AT3BH-AT6BH). The subjects were divided into moderate astigmatism group (46 eyes, 1.5-2.5 D) and high astigmatism group (44 eyes, >2.5 D). The uncorrected distance visual acuity, residual astigmatism and axial position of IOL were observed before operation, 3, 6mo and 1y after operation. Modulation transfer function cutoff (MTF cutoff), Strehl ratio (SR), object scatter index (OSI) were observed by OQAS II to evaluate the objective visual quality of patients.

Results: There was no significant difference in UCVA, residual astigmatism, axial deviation, MTF cutoff, SR and OSI between moderate and high astigmatism group (all >0.05). After 3mo, UCVA, MTF cutoff and SR were significantly increased (all <0.05), residual astigmatism and OSI were significantly decreased (all <0.05). After 3mo, all the indexes remained stable.

Conclusion: Proming toric IOL can effectively treat age-related cataract patients with moderate-to-high regular corneal astigmatism, correcting corneal astigmatism, improving UCVA, ensuring long-term stability in the capsule, and providing patients with better visual quality.
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http://dx.doi.org/10.18240/ijo.2021.02.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840366PMC
February 2021

IL-37 overexpression enhances therapeutic effect of endometrial regenerative cells in concanavalin A-induced hepatitis.

Cytotherapy 2021 Feb 13. Epub 2021 Feb 13.

Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin, China. Electronic address:

Background Aims: Mesenchymal stromal cells and immunosuppressive factor IL-37 can both suppress concanavalin A (Con A)-induced hepatitis in mice. Endometrial regenerative cells (ERCs), novel types of mesenchymal-like stromal cells, possess powerful immunomodulatory effects and are effective in treating various diseases. The aim of this study was to explore the effects of ERCs in suppressing Con A-induced hepatitis and determine whether IL-37 overexpression could enhance the therapeutic effect of ERCs in this process.

Methods: ERCs were extracted from the menstrual blood of healthy female volunteer donors. The IL-37 gene was transferred into ERCs, and the expression of IL-37 in cells was detected by western blot and enzyme-linked immunosorbent assay. Hepatitis was induced by Con A in C57BL/6 mice that were randomly divided into groups treated with phosphate-buffered saline, ERCs, IL-37 or ERCs transfected with the IL-37 gene (IL-37-ERCs). Cell tracking, liver function, histopathological and immunohistological changes, immune cell proportions and levels of cytokines were measured 24 h after Con A administration.

Results: Compared with ERC or IL-37 treatment, IL-37-ERCs further reduced levels of liver enzymes (alanine aminotransferase and aspartate aminotransferase) and improved histopathological changes in the liver. In addition, IL-37-ERC treatment further reduced the proportions of M1 macrophages and CD4 T cells and increased the proportion of regulatory T cells. Moreover, IL-37-ERC treatment resulted in lower levels of IL-12 and interferon gamma, and higher level of transforming growth factor beta.

Conclusions: The results of this study suggest that ERCs can effectively alleviate Con A-induced hepatitis. Furthermore, IL-37 overexpression can significantly enhance the therapeutic efficacy of ERCs by augmenting the immunomodulatory and anti-inflammatory properties of ERCs. This study may provide a promising strategy for treatment of T-cell-dependent hepatitis.
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http://dx.doi.org/10.1016/j.jcyt.2020.12.006DOI Listing
February 2021

Biological features and clinical outcome in infant neuroblastoma: a multicenter experience in Beijing.

Eur J Pediatr 2021 Feb 13. Epub 2021 Feb 13.

Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, Key Laboratory of Major Diseases in Children, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, with 37% of patients diagnosed during infancy. This study is aimed at evaluating the survival outcome in infants diagnosed with neuroblastoma. This was a retrospective cohort study including patients under the age of 12 months with neuroblastoma from four tertiary referral centers in Beijing, China (Beijing Children's Hospital, Beijing Tongren Hospital, Peking University First Hospital, and Capital Institute of Pediatrics). Two hundred and forty-seven infants with neuroblastoma were included (male = 132 and female = 115). 91.1% (n = 225) patients were classified as having low-risk or intermediate-risk disease and 8.9% (n = 22) as having high-risk disease. The most common metastatic site is distant lymph node (n=89, 36.0%), followed by liver (n=57, 23.1%), bone (n=42, 17.0%), bone marrow (n=37, 15.0%), soft tissue (n=25, 10%), and central nervous system (n=4, 1.6%). MYCN amplification was present in 9.9% of tumor samples, chromosome 1p or 11q aberration in 14%. Treatment involved surgery alone in 9.7% of patients (n=24, all with low-risk disease), surgery followed by adjuvant chemotherapy in 50.2% (n=124), neoadjuvant chemotherapy followed by surgery in 40.1% (n=97), and chemotherapy alone in 0.8% (n=2). 4.9% (n=12) patients died, and the major cause of death is disease progression. Three-year event-free and overall survival were 91.6%±2.1% and 97.4%±1.1%, respectively, in patients with low- or intermediate-risk disease, and 58.7%±11.5% and 63.6%±11.2%, respectively, in those with high-risk disease.Conclusions: Infants with neuroblastoma achieve a reasonable clinical outcome when treated with surgery with or without chemotherapy using a risk-stratified approach in China. Such information will facilitate counseling, therapeutic decision-making, and development of adapted standard-of-care guidelines for future patients in the country. What is Known: • NB is a disease of infancy; 37% of patients are diagnosed as infants. • Most children younger than 12 months of age have a good prognosis even in the presence of metastatic disease. What is New: • Infants with neuroblastoma achieve reasonable clinical outcome when treated with surgery with or without chemotherapy using a risk-stratified approach in China. • CNS metastasis in infants with neuroblastoma is very rare at diagnosis and had a worse prognosis than those without metastasis.
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http://dx.doi.org/10.1007/s00431-021-03989-1DOI Listing
February 2021

CircNRIP1 Modulates the miR-515-5p/IL-25 Axis to Control 5-Fu and Cisplatin Resistance in Nasopharyngeal Carcinoma.

Drug Des Devel Ther 2021 27;15:323-330. Epub 2021 Jan 27.

Department of Radiotherapy, Zibo Central Hospital, Zibo, Shandong, People's Republic of China.

Background: The development of drug resistance leads many NPC patients to experience disease relapse following the completion of chemotherapy. It is thus essential that the mechanistic basis for such chemoresistance be clarified in an effort to identify approaches to sensitizing NPC tumors to treatment with cisplatin and related agents.

Methods: A qRT-PCR approach was used to measure the expression of circNRIP1 in NPC, while luciferase assays were used to identify interactions with downstream targets of circNRIP1 activity including miR-515-5p and IL-25. CCK8 assays were also utilized to detect IC50 values for cisplatin and 5-Fu.

Results: The expression of circNRIP1 was significantly increased in the serum of chemoresistant NPC patients. At a functional level, we determined that circNRIP1 is able to sequester miR-515-5p, thereby inhibiting its ability to post-transcriptionally suppress IL-25 expression. We observed a significant negative correlation between the expression of miR-515-5p and circNRIP1 in serum samples from chemoresistant NPC patients, consistent with a functional interaction between these two factors. We further found that 5-Fu and CDDP IC50 values in NPC cells in which circNRIP1 had been knocked down were restored following miR-515-5p inhibitor transfection. Similarly, changes in these IC50 values were reversed in NPC cells transfected with miR-515-5p mimics following the overexpression of IL-25 in these same cells.

Conclusion: These data highlight the circNRIP1/miR-515-5p/IL-25 as a novel regulator of 5-Fu and cisplatin resistance in NPC, suggesting that this pathway may be amenable to therapeutic targeting as an approach to treating this cancer type.
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http://dx.doi.org/10.2147/DDDT.S292180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850406PMC
January 2021

Depth-Quality-Aware Salient Object Detection.

IEEE Trans Image Process 2021 27;30:2350-2363. Epub 2021 Jan 27.

The existing fusion-based RGB-D salient object detection methods usually adopt the bistream structure to strike a balance in the fusion trade-off between RGB and depth (D). While the D quality usually varies among the scenes, the state-of-the-art bistream approaches are depth-quality-unaware, resulting in substantial difficulties in achieving complementary fusion status between RGB and D and leading to poor fusion results for low-quality D. Thus, this paper attempts to integrate a novel depth-quality-aware subnet into the classic bistream structure in order to assess the depth quality prior to conducting the selective RGB-D fusion. Compared to the SOTA bistream methods, the major advantage of our method is its ability to lessen the importance of the low-quality, no-contribution, or even negative-contribution D regions during RGB-D fusion, achieving a much improved complementary status between RGB and D. Our source code and data are available online at https://github.com/qdu1995/DQSD.
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http://dx.doi.org/10.1109/TIP.2021.3052069DOI Listing
January 2021

Palladium-Catalyzed C2-Regioselective Perfluoroalkylation of the Free (NH)-Heteroarenes.

J Org Chem 2021 Feb 12;86(3):2840-2853. Epub 2021 Jan 12.

College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, 30 Puzhu Road South, Nanjing 211816, P. R. China.

A highly regioselective and atom-efficient strategy for the construction of fused free (NH) heteroarenes through a palladium-catalyzed perfluoroalkyl insertion reaction has been accomplished. This protocol employed multiple iodofluoroalkanes as practical and available perfluoroalkyl sources to provide an operationally simple and versatile route for the synthesis of perfluoroalkylated indoles. Moreover, indoles without the assistance of guide groups were utilized as substrates, achieving C(sp)-H site-selective functionalization of indoles in yields up to 95%. Furthermore, this protocol was also used for late-stage C2 perfluoroalkylation of bioactive compounds such as auxin, tryptophan, and melatonin analogues.
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http://dx.doi.org/10.1021/acs.joc.0c02782DOI Listing
February 2021

Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections.

Nat Commun 2021 01 11;12(1):264. Epub 2021 Jan 11.

CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 Å resolution, revealing the conformational space of the antigen-antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections.
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http://dx.doi.org/10.1038/s41467-020-20465-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801428PMC
January 2021

A Global-Local Self-Adaptive Network for Drone-View Object Detection.

IEEE Trans Image Process 2021 5;30:1556-1569. Epub 2021 Jan 5.

Directly benefiting from the deep learning methods, object detection has witnessed a great performance boost in recent years. However, drone-view object detection remains challenging for two main reasons: (1) Objects of tiny-scale with more blurs w.r.t. ground-view objects offer less valuable information towards accurate and robust detection; (2) The unevenly distributed objects make the detection inefficient, especially for regions occupied by crowded objects. Confronting such challenges, we propose an end-to-end global-local self-adaptive network (GLSAN) in this paper. The key components in our GLSAN include a global-local detection network (GLDN), a simple yet efficient self-adaptive region selecting algorithm (SARSA), and a local super-resolution network (LSRN). We integrate a global-local fusion strategy into a progressive scale-varying network to perform more precise detection, where the local fine detector can adaptively refine the target's bounding boxes detected by the global coarse detector via cropping the original images for higher-resolution detection. The SARSA can dynamically crop the crowded regions in the input images, which is unsupervised and can be easily plugged into the networks. Additionally, we train the LSRN to enlarge the cropped images, providing more detailed information for finer-scale feature extraction, helping the detector distinguish foreground and background more easily. The SARSA and LSRN also contribute to data augmentation towards network training, which makes the detector more robust. Extensive experiments and comprehensive evaluations on the VisDrone2019-DET benchmark dataset and UAVDT dataset demonstrate the effectiveness and adaptivity of our method. Towards an industrial application, our network is also applied to a DroneBolts dataset with proven advantages. Our source codes have been available at https://github.com/dengsutao/glsan.
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http://dx.doi.org/10.1109/TIP.2020.3045636DOI Listing
January 2021

Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM.

Sci Adv 2021 01 1;7(1). Epub 2021 Jan 1.

State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China.

The recent outbreaks of SARS-CoV-2 pose a global health emergency. The SARS-CoV-2 trimeric spike (S) glycoprotein interacts with the human ACE2 receptor to mediate viral entry into host cells. We report the cryo-EM structures of a tightly closed SARS-CoV-2 S trimer with packed fusion peptide and an ACE2-bound S trimer at 2.7- and 3.8-Å resolution, respectively. Accompanying ACE2 binding to the up receptor-binding domain (RBD), the associated ACE2-RBD exhibits continuous swing motions. Notably, the SARS-CoV-2 S trimer appears much more sensitive to the ACE2 receptor than the SARS-CoV S trimer regarding receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2. Our findings depict the mechanism of ACE2-induced S trimer conformational transitions from the ground prefusion state toward the postfusion state, facilitating development of anti-SARS-CoV-2 vaccines and therapeutics.
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http://dx.doi.org/10.1126/sciadv.abe5575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775788PMC
January 2021

Hand anthropometry and its relation to grip/pinch strength in children aged 5 to 13 years.

J Int Med Res 2020 Dec;48(12):300060520970768

Department of Children Health Care, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.

Objective: To evaluate the development level of children's physiological hand shape indicators and their relationship with grip/pinch strength.

Methods: Hand shape and grip/pinch strength in 1255 Chinese children aged 5 to 13 years were prospectively measured. Development curves of physiological hand shape indicators and grip/pinch strength were constructed.

Results: The physiological hand shape indicators (full length, middle finger length, width, and wrist thickness) and grip/pinch strength of boys and girls increased with age and showed statistically significant differences at different ages. In most age groups, hand shape indicators and grip/pinch strength were larger in boys than in girls of the same age. After puberty, the physiological hand shape indicators and grip/pinch strength increased more rapidly in girls than in boys of the same age, and the differences gradually decreased thereafter. Moreover, a significant difference in pinch strength between the right and left hands was observed in most age groups. Pearson correlation analysis showed that the physiological hand shape indicators were significantly positively correlated with grip/pinch strength, height, weight, and body mass index.

Conclusions: This study revealed the relationship between physiological hand shape indicators and grip/pinch strength and provided reference ranges of physiological hand shape indicators and grip/pinch strength for children.
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http://dx.doi.org/10.1177/0300060520970768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720326PMC
December 2020

Inhibitory Effect of Delphinidin on Oxidative Stress Induced by HO in HepG2 Cells.

Oxid Med Cell Longev 2020 20;2020:4694760. Epub 2020 Nov 20.

Xiangya School of Public Health, Central South University, Changsha 410078, China.

Chronic liver diseases (CLDs) are correlated with oxidative stress induced by the accumulation of intracellular reactive oxygen species (ROS). In this study, we employed HepG2, a human liver carcinoma cell line containing many antioxidant enzymes, to explore the function of delphinidin against oxidative stress induced by HO and to provide scientific data of the molecular mechanism. Cells were pretreated with different concentrations of delphinidin (10 mol/L, 20 mol/L, and 40 mol/L) for 2 h before treatment with 750 M HO for 1 h. The results showed that HO decreased the survival rate of HepG2 cells and increased the level of ROS, but delphinidin pretreatment could possess the opposite result. At the same time, the expression of Nrf2 was enhanced by the delphinidin pretreatment. This was because delphinidin promoted Nrf2 nuclear translocation and inhibited its degradation, which led to the increase expression of antioxidant protein HO-1 (Nrf2-related phase II enzyme heme oxygenase-1). Besides, we found that delphinidin could significantly alleviate the reduction of Nrf2 protein levels and the accumulation of intracellular ROS levels in Nrf2 knockdown HepG2 cells. In conclusion, our study suggested that delphinidin, as an effective antioxidant, protected HepG2 cells from oxidative stress by regulating the expression of Nrf2/HO-1.
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http://dx.doi.org/10.1155/2020/4694760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700032PMC
November 2020

Data-Level Recombination and Lightweight Fusion Scheme for RGB-D Salient Object Detection.

IEEE Trans Image Process 2021 23;30:458-471. Epub 2020 Nov 23.

Existing RGB-D salient object detection methods treat depth information as an independent component to complement RGB and widely follow the bistream parallel network architecture. To selectively fuse the CNN features extracted from both RGB and depth as a final result, the state-of-the-art (SOTA) bistream networks usually consist of two independent subbranches: one subbranch is used for RGB saliency, and the other aims for depth saliency. However, depth saliency is persistently inferior to the RGB saliency because the RGB component is intrinsically more informative than the depth component. The bistream architecture easily biases its subsequent fusion procedure to the RGB subbranch, leading to a performance bottleneck. In this paper, we propose a novel data-level recombination strategy to fuse RGB with D (depth) before deep feature extraction, where we cyclically convert the original 4-dimensional RGB-D into DGB, RDB and RGD. Then, a newly lightweight designed triple-stream network is applied over these novel formulated data to achieve an optimal channel-wise complementary fusion status between the RGB and D, achieving a new SOTA performance.
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http://dx.doi.org/10.1109/TIP.2020.3037470DOI Listing
November 2020

Corrigendum to "Prime-Boost Vaccination Using Chemokine-Fused gp120 DNA and HIV Envelope Peptides Activates Both Immediate and Long-Term Memory Cellular Responses in Rhesus Macaques".

Biomed Res Int 2020 29;2020:5471638. Epub 2020 Oct 29.

Department of Lymphoma and Myeloma, M. D. Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA.

[This corrects the article DOI: 10.1155/2010/860160.].
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http://dx.doi.org/10.1155/2020/5471638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648672PMC
October 2020

Gene expression profile of lipopolysaccharide‑induced apoptosis of nucleus pulposus cells reversed by syringic acid.

Mol Med Rep 2020 Dec 23;22(6):5012-5022. Epub 2020 Oct 23.

Department of Rehabilitation Medicine, Langdong Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530028, P.R. China.

Apoptosis of nucleus pulposus (NP) cells has an important role in the process of intervertebral disc degeneration (IDD), and the search for novel compounds to prevent apoptosis from occurring is urgently required. In the present study, syringic acid (SyrA) was found to exhibit no cytotoxicity on NP cells, and was able to reverse the cytotoxicity, as well as the abnormal expression of Bcl‑2 and caspase‑3, that were induced by lipopolysaccharide (LPS). The transcriptomes of each group were then analyzed using RNA‑Seq. A total of 65 differentially expressed genes (DEGs) were identified in LPS‑stimulated groups (LPS group vs. control group), 819 DEGs were identified in the SyrA‑reversed groups (SyrA plus LPS group vs. LPS group), and a further 25 DEGs were identified in the SyrA plus LPS group compared with the control group. Reverse transcription‑quantitative PCR validation indicated that the alterations in expression of uroplakin 3B‑like 1 (UPK3BL1), voltage‑dependent calcium channel subunit α‑2/δ‑1 (CACNA2D1) and polo‑like kinase 4 (PLK4) were consistent with the corresponding results of RNA‑Seq, and that these genes were involved in both LPS‑stimulation and SyrA‑reversion processes. Kyoto Encyclopedia of Genes and Genomes analyses indicated that the DEGs in SyrA‑reversed groups were involved in, amongst other pathways, 'Autophagy‑other' and 'Apoptosis‑multiple species'. In conclusion, the addition of SyrA to the NP cells co‑incubated with LPS appeared to help prevent the abnormal expression of mRNAs and apoptosis that had been identified in NP cells incubated with LPS alone. The potential mechanism underlying the reversion of SyrA might be attributed to the regulation of CACNA2D1 and PLK4.
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http://dx.doi.org/10.3892/mmr.2020.11632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646953PMC
December 2020

Machine learning and serving of discrete field theories.

Authors:
Hong Qin

Sci Rep 2020 Nov 9;10(1):19329. Epub 2020 Nov 9.

Plasma Physics Laboratory, Princeton University, Princeton, NJ, 08543, USA.

A method for machine learning and serving of discrete field theories in physics is developed. The learning algorithm trains a discrete field theory from a set of observational data on a spacetime lattice, and the serving algorithm uses the learned discrete field theory to predict new observations of the field for new boundary and initial conditions. The approach of learning discrete field theories overcomes the difficulties associated with learning continuous theories by artificial intelligence. The serving algorithm of discrete field theories belongs to the family of structure-preserving geometric algorithms, which have been proven to be superior to the conventional algorithms based on discretization of differential equations. The effectiveness of the method and algorithms developed is demonstrated using the examples of nonlinear oscillations and the Kepler problem. In particular, the learning algorithm learns a discrete field theory from a set of data of planetary orbits similar to what Kepler inherited from Tycho Brahe in 1601, and the serving algorithm correctly predicts other planetary orbits, including parabolic and hyperbolic escaping orbits, of the solar system without learning or knowing Newton's laws of motion and universal gravitation. The proposed algorithms are expected to be applicable when the effects of special relativity and general relativity are important.
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http://dx.doi.org/10.1038/s41598-020-76301-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652943PMC
November 2020

Treatment and outcomes of 1041 pediatric patients with neuroblastoma who received multidisciplinary care in China.

Pediatr Investig 2020 Sep 27;4(3):157-167. Epub 2020 Sep 27.

Department of Otorhinolaryngology Head and Neck Surgery Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.

Importance: Neuroblastoma is the most common extracranial malignant solid tumor in children. Multidisciplinary care is critical to improving the survival of pediatric patients with neuroblastoma.

Objective: To systematically summarize the clinical characteristics of children with neuroblastoma and evaluate their prognosis with multidisciplinary care provided in a single center.

Methods: This retrospective study analyzed the clinical data of 1041 patients with neuroblastoma who were diagnosed, treated, and followed-up in the Hematology-Oncology Center of Beijing Children's Hospital from 2007 to 2019.

Results: The median age at diagnosis was 34 months; 80.8% of the patients were younger than 5 years of age. Notably, 243 patients (23.3%) were classified as low-risk, 249 patients (23.9%) were classified as intermediate-risk, and 549 (52.7%) were classified as high-risk. Furthermore, 956 patients underwent surgical resections; 986 (94.7%) patients received chemotherapy; and 176 patients with high-risk neuroblastoma received hematopoietic stem cell transplantation. The 5-year event-free survival (EFS) rate was 91.3% and 5-year overall survival (OS) rate was 97.5% in low-risk group; in the intermediate-risk group, these rates were 85.1% and 96.7%, respectively, while they were 37.7% and 48.9% in the high-risk group ( 0.001 for both). The 5-year EFS and OS rates were significantly higher in patients diagnosed between 2015 and 2019 than in patients diagnosed between 2007 and 2014 ( 0.001). In total, 278 patients (26.7%) exhibited tumor relapse or progression; the median interval until relapse or progression was 14 months. Of the 233 patients who died, 83% died of relapse or progression of neuroblastoma and 4.3% died of therapy-related complications.

Interpretation: The 5-year OS rate was low in high-risk patients, compared with low-and intermediate-risk patients. Multidisciplinary care is critical for improvement of survival in pediatric patients with neuroblastoma. Additional treatment strategies should be sought to improve the prognosis of patients with high-risk neuroblastoma.
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http://dx.doi.org/10.1002/ped4.12214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520112PMC
September 2020

The Cerebroventricular Environment Modifies CAR T Cells for Potent Activity against Both Central Nervous System and Systemic Lymphoma.

Cancer Immunol Res 2021 Jan 22;9(1):75-88. Epub 2020 Oct 22.

Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California.

Lymphomas with central nervous system (CNS) involvement confer a worse prognosis than those without CNS involvement, and patients currently have limited treatment options. T cells genetically engineered with CD19-targeted chimeric antigen receptors (CAR) are effective against B-cell malignancies and show tremendous potential in the treatment of systemic lymphoma. We aimed to leverage this strategy toward a more effective therapy for patients with lymphoma with CNS disease. NOD- IL2Rgamma (NSG) mice with CNS and/or systemic lymphoma were treated with CD19-CAR T cells via intracerebroventricular (ICV) or intravenous (IV) injection. CAR T cells isolated after treatment were rigorously examined for phenotype, gene expression, and function. We observed that CAR T cells infused ICV, but not IV, completely and durably eradicated both CNS and systemic lymphoma. CAR T cells delivered ICV migrated efficiently to the periphery, homed to systemic tumors, and expanded , leading to complete elimination of disease and resistance to tumor rechallenge. Mechanistic studies indicated that ICV-delivered CAR T cells are conditioned by exposure to cerebrospinal fluid in the ICV environment for superior antilymphoma activity and memory function compared with IV-delivered CAR T cells. Further analysis suggested that manipulating cellular metabolism or preactivating therapeutic CAR T cells with antigen may improve the efficacy of CAR T cells Our demonstration that ICV-delivered CD19-CAR T cells had activity against CNS and systemic lymphoma could offer a valuable new strategy for treatment of B-cell malignancies with CNS involvement.
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http://dx.doi.org/10.1158/2326-6066.CIR-20-0236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008993PMC
January 2021

Simulating pitch angle scattering using an explicitly solvable energy-conserving algorithm.

Phys Rev E 2020 Sep;102(3-1):033302

Princeton Plasma Physics Laboratory and Department of Astrophysical Sciences, Princeton University, Princeton NJ 08540, USA.

Particle distribution functions evolving under the Lorentz operator can be simulated with the Langevin equation for pitch-angle scattering. This approach is frequently used in particle-based Monte-Carlo simulations of plasma collisions, among others. However, most numerical treatments do not guarantee energy conservation, which may lead to unphysical artifacts such as numerical heating and spectra distortions. We present a structure-preserving numerical algorithm for the Langevin equation for pitch-angle scattering. Similar to the well-known Boris algorithm, the proposed numerical scheme takes advantage of the structure-preserving properties of the Cayley transform when calculating the velocity-space rotations. The resulting algorithm is explicitly solvable, while preserving the norm of velocities down to machine precision. We demonstrate that the method has the same order of numerical convergence as the traditional stochastic Euler-Maruyama method. The numerical scheme is benchmarked by simulating the pitch-angle scattering of a particle beam and comparing with the analytical solution. Benchmark results show excellent agreement with theoretical predictions, showcasing the remarkable long-time accuracy of the proposed algorithm.
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http://dx.doi.org/10.1103/PhysRevE.102.033302DOI Listing
September 2020

A long non-coding RNA specifically expressed in early embryos programs the metabolic balance in adult mice.

Biochim Biophys Acta Mol Basis Dis 2021 01 13;1867(1):165988. Epub 2020 Oct 13.

Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai 200438, China. Electronic address:

Many Long non-coding RNAs (lncRNAs) are specifically expressed in early embryos, but the physiological functions of most of them remain largely unknown. Here, we show that deficiency of lncenc1, an early embryo-specific lncRNA, altering glucose and lipid balance in adult mice. Newly weaned lncenc1-deficient mice prefer to use lipids as a fuel source. When mice were fed a normal chow diet (NCD), glucose intolerance and insulin resistance were observed in adult lncenc1-deficient mice. Under high-fat diet (HFD) conditions, however, lncenc1-deficient mice became healthier and could resist food-induced obesity and metabolic disturbances. Furthermore, AKT/mTOR-regulated lipogenesis in liver was reduced in lncenc1-deficient mice fed a HFD. MEFs lacking lncenc1 showed impaired glycolysis and lipogenesis, suggesting that the metabolic defects may already exist in embryos. Our study demonstrated the essential roles of lncenc1 in adult metabolism, providing experimental data that support the "fetal origin" of adult metabolic disorders.
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http://dx.doi.org/10.1016/j.bbadis.2020.165988DOI Listing
January 2021

Coblopasvir and sofosbuvir for treatment of chronic hepatitis C virus infection in China: A single-arm, open-label, phase 3 trial.

Liver Int 2020 11 13;40(11):2685-2693. Epub 2020 Oct 13.

Department of Hepatology, the First Hospital of Jilin University, Changchun, China.

Background & Aim: An affordable, pangenotypic regimen remains as an unmet medical need for chronic hepatitis C patients in China. This single-arm, open-label, multicenter, phase 3 trial evaluated the efficacy and safety of coblopasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic hepatitis C virus (HCV) infection.

Methods: Treatment-naïve and interferon-experienced adult patients, including those with advanced fibrosis (F3) or compensated cirrhosis (F4), were treated with a universal, combinational regimen of coblopasvir 60 mg and sofosbuvir 400 mg, once daily, for 12 weeks. The primary efficacy endpoint was sustained virological response at post-treatment week 12 (SVR12).

Results: Overall, 371 patients (men, 51%; age, 47 ± 11 years; genotype 1a < 1%, 1b 48%, 2a 26%, 3a 6%, 3b 7% and 6 12%) were enrolled from 19 sites. Fifty-one patients (14%) had F3, 39 patients (11%) had F4 and 39 patients (11%) were interferon experienced. The overall SVR12 was 97% (95% CI, [94%, 98%]) for the full analysis set and was equal to or above 90% for all predefined subsets. Ten patients (3%) experienced virological relapse and two patients did not complete follow-up. No adverse events (AEs) occurred at a frequency ≥5%, and the most often reported AEs (≥1%) were neutropenia and fatigue. The majority of AEs were mild to moderate and transient without specific medical intervention.

Conclusions: The universal, pangenotypic combo of coblopasvir plus sofosbuvir is an efficacious and safe treatment for Chinese patients monoinfected with HCV of genotype 1, 2, 3 and 6, including those with compensated cirrhosis.

Lay Summary: The regimen of coblopasvir and sofosbuvir is a safe and effective treatment for Chinese patients with genotype 1, 2, 3 and 6 HCV infection, including those with compensated cirrhosis. Therefore, this regimen would be a novel choice of treatment for this patient population.
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http://dx.doi.org/10.1111/liv.14633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702130PMC
November 2020