Publications by authors named "Tong Yu"

389 Publications

Histone Arginine Methyltransferase CARM1-Mediated H3R26me2 Is Essential for Morula-to-Blastocyst Transition in Pigs.

Front Cell Dev Biol 2021 2;9:678282. Epub 2021 Jun 2.

Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.

Coactivator-associated arginine methyltransferase 1 (CARM1) is involved in both establishment of first pluripotent lineage and pluripotency maintenance of embryonic stem cells (ESCs) in mice. However, the histone substrates and role of CARM1 in early embryonic development remain largely unknown. Here, we show that CARM1 specifically catalyzes H3R26me2 to promote porcine blastocyst formation. The putative histone substrates of CARM1, including H3R2me2, H3R17me2, and H3R26me2, are present in pig early embryos. The changes of mRNA during early embryogenesis parallel that of H3R26me2. Functional studies using a combinational approach of chemical inhibition and RNA interference (RNAi) showed that catalytic activity inhibition of CARM1 protein or knockdown (KD) of mRNA did not alter the levels of both H3R2me2 and H3R17me2, but significantly reduced H3R26me2 levels in porcine embryos. Furthermore, CARM1 inhibition or KD did not affect embryo development to the 2-cell, 4-cell, 8-cell, and morula stages, but severely compromised blastocyst development. knocked down embryos that developed to the blastocyst stage had fewer total cells, inner cell mass (ICM), and trophectoderm (TE) cells. Mechanistically, single embryo RNA-sequencing analysis revealed that KD altered the transcriptome characterized by downregulation of key genes associated with Hippo and PI3K-AKT signaling pathways. Taken together, these results demonstrate that CARM1 specifically catalyzes H3R26me2 in porcine embryos and participates in blastocyst development.
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http://dx.doi.org/10.3389/fcell.2021.678282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206646PMC
June 2021

Research progress of dual inhibitors targeting crosstalk between histone epigenetic modulators for cancer therapy.

Eur J Med Chem 2021 Jun 1;222:113588. Epub 2021 Jun 1.

School of Pharmacy, Xinxiang Medical University, 453003, Xinxiang, Henan Province, PR China. Electronic address:

Abnormal epigenetics is a critical hallmark of human cancers. Anticancer drug discovery directed at histone epigenetic modulators has gained impressive advances with six drugs available for cancer therapy and numerous other candidates undergoing clinical trials. However, limited therapeutic profile, drug resistance, narrow safety margin, and dose-limiting toxicities pose intractable challenges for their clinical utility. Because histone epigenetic modulators undergo intricate crosstalk and act cooperatively to shape an aberrant epigenetic profile, co-targeting histone epigenetic modulators with a different mechanism of action has rapidly emerged as an attractive strategy to overcome the limitations faced by the single-target epigenetic inhibitors. In this review, we summarize in detail the crosstalk of histone epigenetic modulators in regulating gene transcription and the progress of dual epigenetic inhibitors targeting this crosstalk.
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http://dx.doi.org/10.1016/j.ejmech.2021.113588DOI Listing
June 2021

Delayed Rise of Oral Fluid Antibodies, Elevated BMI, and Absence of Early Fever Correlate With Longer Time to SARS-CoV-2 RNA Clearance in a Longitudinally Sampled Cohort of COVID-19 Outpatients.

Open Forum Infect Dis 2021 Jun 16;8(6):ofab195. Epub 2021 Apr 16.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Background: Sustained molecular detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the upper respiratory tract (URT) in mild to moderate coronavirus disease 2019 (COVID-19) is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection.

Methods: Ninety-five symptomatic outpatients self-collected midturbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models.

Results: Viral RNA clearance, as measured by SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR), in 507 URT samples occurred a median (interquartile range) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR-positive samples tested. All participants but 1 with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (adjusted hazard ratio [aHR], 0.96; 95% CI, 0.92-0.99; = .020) and body mass index (BMI) ≥25 kg/m (aHR, 0.37; 95% CI, 0.18-0.78; = .009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as 1 of first 3 COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR, 2.06; 95% CI, 1.02-4.18; = .044).

Conclusions: We demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.
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http://dx.doi.org/10.1093/ofid/ofab195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083254PMC
June 2021

The role of iron homeostasis and iron-mediated ROS in cancer.

Am J Cancer Res 2021 15;11(5):1895-1912. Epub 2021 May 15.

Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College Hangzhou 310014, Zhejiang Province, P. R. China.

As an important trace element, iron plays an essential role in many biology processes like cell proliferation, metabolism, and mitochondrial function. However, the disruption of iron homeostasis tends to cells death and human diseases due to it servers as mediator to promote the production of reactive oxygen species (ROS). In this review, first we introduced the mechanism of complex iron-mediated ROS involved in apoptosis, necroptosis, ferroptosis and pyroptosis. Next, we discussed the controversial role of excess iron and iron deficiency in tumor. Finally, we discussed the anti-cancer effects of iron on both sides, and novel iron-related strategies. This review outlined the mechanisms and regulation of iron homeostasis and iron-mediated ROS in tumors, and discussed the iron-related treatments.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167679PMC
May 2021

Comprehensive analysis of SSRs and database construction using all complete gene-coding sequences in major horticultural and representative plants.

Hortic Res 2021 Jun 1;8(1):122. Epub 2021 Jun 1.

School of Life Sciences/Library, North China University of Science and Technology, Tangshan, Hebei, 063210, China.

Simple sequence repeats (SSRs) are one of the most important genetic markers and widely exist in most species. Here, we identified 249,822 SSRs from 3,951,919 genes in 112 plants. Then, we conducted a comprehensive analysis of these SSRs and constructed a plant SSR database (PSSRD). Interestingly, more SSRs were found in lower plants than in higher plants, showing that lower plants needed to adapt to early extreme environments. Four specific enriched functional terms in the lower plant Chlamydomonas reinhardtii were detected when it was compared with seven other higher plants. In addition, Guanylate_cyc existed in more genes of lower plants than of higher plants. In our PSSRD, we constructed an interactive plotting function in the chart interface, and users can easily view the detailed information of SSRs. All SSR information, including sequences, primers, and annotations, can be downloaded from our database. Moreover, we developed Web SSR Finder and Batch SSR Finder tools, which can be easily used for identifying SSRs. Our database was developed using PHP, HTML, JavaScript, and MySQL, which are freely available at http://www.pssrd.info/ . We conducted an analysis of the Myb gene families and flowering genes as two applications of the PSSRD. Further analysis indicated that whole-genome duplication and whole-genome triplication played a major role in the expansion of the Myb gene families. These SSR markers in our database will greatly facilitate comparative genomics and functional genomics studies in the future.
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http://dx.doi.org/10.1038/s41438-021-00562-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167114PMC
June 2021

Aptamer and Peptide-Modified Lipid-Based Drug Delivery Systems in Application of Combined Sequential Therapy of Hepatocellular Carcinoma.

ACS Biomater Sci Eng 2021 06 28;7(6):2558-2568. Epub 2021 May 28.

Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, P. R. China.

Hepatocellular carcinoma (HCC) is known as the most common malignancy of the hepatobiliary system with a continued increase in incidence but limited therapeutic options. Nanomedicine has provided a promising strategy through engineered nanocarriers that are capable of targeting therapeutic agents specifically to tumor cells. In this research, two aptamer/peptide-modified lipid-based drug delivery systems (A54-PEG-SLN/OXA and A15-PEG-SLN/SAL) were developed as a sequential therapeutic strategy to conquer specific hepatocellular carcinoma. The nanomedicine A54-PEG-SLN/OXA was able to target specific hepatocellular carcinoma cell BEL-7402 and exhibited a strong targeting ability and antitumor efficiency both and . The A15-PEG-SLN/SAL could target and penetrate deeply to the spheroid composed of CD133+ cancer cells. In the study of developing a sequential therapeutic strategy, we demonstrated that A54-PEG-SLN/OXA could kill tumor cells and expose CD133+ cancer cells. After the administration of A15-PEG-SLN/SAL, the growth of the tumors was significantly inhibited. In conclusion, the aptamer/peptide-modified lipid-based drug delivery systems, A54-PEG-SLN/OXA and A15-PEG-SLN/SAL, could specifically target carcinoma cells and had an evident antitumor effect when administrated sequentially.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00357DOI Listing
June 2021

Multi-task temporal convolutional networks for joint recognition of surgical phases and steps in gastric bypass procedures.

Int J Comput Assist Radiol Surg 2021 May 19. Epub 2021 May 19.

ICube, University of Strasbourg, CNRS, IHU Strasbourg, France.

Purpose: Automatic segmentation and classification of surgical activity is crucial for providing advanced support in computer-assisted interventions and autonomous functionalities in robot-assisted surgeries. Prior works have focused on recognizing either coarse activities, such as phases, or fine-grained activities, such as gestures. This work aims at jointly recognizing two complementary levels of granularity directly from videos, namely phases and steps.

Methods: We introduce two correlated surgical activities, phases and steps, for the laparoscopic gastric bypass procedure. We propose a multi-task multi-stage temporal convolutional network (MTMS-TCN) along with a multi-task convolutional neural network (CNN) training setup to jointly predict the phases and steps and benefit from their complementarity to better evaluate the execution of the procedure. We evaluate the proposed method on a large video dataset consisting of 40 surgical procedures (Bypass40).

Results: We present experimental results from several baseline models for both phase and step recognition on the Bypass40. The proposed MTMS-TCN method outperforms single-task methods in both phase and step recognition by 1-2% in accuracy, precision and recall. Furthermore, for step recognition, MTMS-TCN achieves a superior performance of 3-6% compared to LSTM-based models on all metrics.

Conclusion: In this work, we present a multi-task multi-stage temporal convolutional network for surgical activity recognition, which shows improved results compared to single-task models on a gastric bypass dataset with multi-level annotations. The proposed method shows that the joint modeling of phases and steps is beneficial to improve the overall recognition of each type of activity.
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http://dx.doi.org/10.1007/s11548-021-02388-zDOI Listing
May 2021

Novel Mutations in Chinese Patients with Multiple Osteochondromas Identified Using Whole Exome Sequencing.

Genet Test Mol Biomarkers 2021 May;25(5):361-367

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Multiple osteochondromas (MO) are an autosomal-dominant disease characterized by the growth of multiple cartilage-capped prominences in the growth plate region of the metaphysis in long and flat bones. To detect genetic mutations related to MO, a three-generation Chinese family with MO was evaluated using whole exome sequencing for mutation screening. The candidate pathogenic mutation was validated by Sanger sequencing. A novel frameshift (NM_000401.3:c.1321del:p.Leu441TrpfsTer28) in exon 8 of the exotosin 2 () gene was identified in two affected individuals. Codons 441 and 468 in the gene are highly conserved among vertebrates as demonstrated by multiple sequence alignment. The c.1321 del C resulted in an amino acid change at codon 441, which generated a premature stop codon at position 468, causing complete loss of the glycosyltransferase domain. A novel frameshift mutation c.1321delC detected in the gene may help in prenatal genetic screening and early diagnosis of MO.
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http://dx.doi.org/10.1089/gtmb.2020.0317DOI Listing
May 2021

The long non-coding RNA PFI protects against pulmonary fibrosis by interacting with splicing regulator SRSF1.

Cell Death Differ 2021 May 12. Epub 2021 May 12.

Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, P. R. China.

Pulmonary fibrosis (PF) is a type of interstitial pneumonia with complex etiology and high mortality, characterized by progressive scarring of the alveolar interstitium and myofibroblastic lesions. Recently, there has been growing appreciation of the importance of long non-coding RNAs (lncRNAs) in organ fibrosis. The aim of this study was to investigate the role of lncRNAs in lung fibrosis. We used a qRT-PCR assay to identify dysregulated lncRNAs in the lungs of mice with experimental, bleomycin (BLM)-induced pulmonary fibrosis, and a series of molecular assays to assess the role of the novel lncRNA NONMMUT060091, designated as pulmonary fibrosis inhibitor (PFI), which was significantly downregulated in lung fibrosis. Functionally, knockdown of endogenous PFI by smart silencer promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in primary mouse lung fibroblasts (MLFs). In contrast, overexpression of PFI partially abrogated TGF-β1-induced fibrogenesis both in MLFs and in the human fetal lung fibroblast MRC-5 cells. Similarly, PFI overexpression attenuated BLM-induced pulmonary fibrosis compared with wild type (WT) mice. Mechanistically, using chromatin isolation by RNA purification-mass spectrometry (ChIRP-MS) and an RNA pull-down assay, PFI was found to directly bind Serine/arginine-rich splicing factor 1 (SRSF1), and to repress its expression and pro-fibrotic activity. Furthermore, silencing of SRSF1 inhibited TGF-β1-induced proliferation, differentiation, and ECM deposition in MRC-5 cells by limiting the formation of the EDA+Fn1 splicing isoform; whereas forced expression of SRSF1 by intratracheal injection of adeno-associated virus 5 (AAV5) ablated the anti-fibrotic effect of PFI in BLM-treated mice. Overall, these data reveal that PFI mitigated pulmonary fibrosis through negative regulation of the expression and activity of SRSF1 to decrease the formation of the EDA+Fn1 splicing isoform, and suggest that PFI and SRSF1 may serve as potential targets for the treatment of lung fibrosis.
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http://dx.doi.org/10.1038/s41418-021-00792-1DOI Listing
May 2021

Synthesis of large-area monolayer and few-layer MoSe continuous films by chemical vapor deposition without hydrogen assistance and formation mechanism.

Nanoscale 2021 May;13(19):8922-8930

Tianjin Key Laboratory of Photoelectric Materials and Devices, School of Materials Science and Engineering, Tianjin University of Technology, Tianjin 300384, China. and Key Laboratory of Display Materials and Photoelectric Devices, National Demonstration Center for Experimental Function Materials Education, Institute of Functional Crystal, Tianjin University of Technology, Ministry of Education, Tianjin 300384, China.

Two dimensional (2D) MoSe2 with a layered structure has attracted extensive research due to its excellent electronic and optical properties. The controlled synthesis of large-scale and high-quality MoSe2 is highly desirable but still remains challenging. Ambient pressure chemical vapor deposition (APCVD) is an excellent method for the synthesis of 2D materials but the inevitable use of hydrogen during the growth and the easy formation of cracks in the ultrathin films still need to be solved. In the present work, we reported the synthesis of large-area continuous MoSe2 films with different layers by the APCVD method without the assistance of hydrogen on SiO2/Si substrates just by raising the reaction temperature of Se. The synthesized continuous MoSe2 films can reach several centimeters, which can be seen clearly by naked eyes, and, more importantly, the size of the monolayer film can reach up to 3 mm. The morphology, structural characteristics, and optical properties of the synthesized MoSe2 films have been investigated, demonstrating good performance and high crystallinity of the films. Raman spectra give the empirical expression of the frequency difference between E2g1 and A1g dependence of the layer number (N = 1-10 L) for CVD grown MoSe2, which is useful in layer number identification. Further, the formation mechanism of the MoSe2 continuous film is of interest as a fundamental scientific problem and needs to be studied. We proposed the wing model, boundary layer theory, and diffusion theory to account quantitatively for the formation behavior of the MoSe2 film. The presented facile growth method and theoretical model are useful to synthesize other ultrathin transition metal dichalcogenide films and understand the formation behaviors of the systems.
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http://dx.doi.org/10.1039/d1nr00552aDOI Listing
May 2021

Ufmylation regulates granulosa cell apoptosis via ER stress but not oxidative stress during goat follicular atresia.

Theriogenology 2021 Jul 22;169:47-55. Epub 2021 Apr 22.

College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, China; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, 712100, China. Electronic address:

Follicular atresia is primarily caused by granulosa cell (GC) apoptosis, although the mechanisms are largely unknown. Ufmylation is a recently identified ubiquitin-like post-translational modifier that plays an important role in cell proliferation and apoptosis. The purpose of this study was to investigate the effects of Ufmylation on GC apoptosis during goat follicular atresia. Ubiquitin-fold modifier 1 (UFM1) and its target DDRGK domain containing 1 (DDRGK1) proteins were identified in granulosa cells (GCs) isolated from all stages of preantral follicles and from healthy (HF), early atretic (EF) and progressed atretic (PF) antral follicles. The expression levels were higher in GCs derived from antral atretic follicles than healthy follicles. Although the viability of GCs was not affected after overexpression of UFM1, siRNA-mediated UFM1 silencing significantly inhibited GC proliferation and induced apoptosis. Notably, components of the ufmylation pathway were significantly upregulated in GCs induced by the ER stress agent tunicamycin (Tm) and thapsigargin (Tg), but not affected by oxidative stress inducer HO. Furthermore, UFM1 silencing markedly increased the apoptosis of GCs upon Tg treatment by stimulating the ER stress-related gene expression. Our results provide evidence that UFM1 and its target DDRGK1 are expressed in the goat GCs during follicular development and atresia, and ufmylation may play an important role in the prevention of ER stress but not oxidative stress-induced GCs apoptosis.
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http://dx.doi.org/10.1016/j.theriogenology.2021.04.009DOI Listing
July 2021

Unveiling Cancer Metabolism through Spontaneous and Coherent Raman Spectroscopy and Stable Isotope Probing.

Cancers (Basel) 2021 Apr 5;13(7). Epub 2021 Apr 5.

Department of Engineering Science, University of Oxford, Oxford OX1 3PJ, UK.

Metabolic reprogramming is a common hallmark in cancer. The high complexity and heterogeneity in cancer render it challenging for scientists to study cancer metabolism. Despite the recent advances in single-cell metabolomics based on mass spectrometry, the analysis of metabolites is still a destructive process, thus limiting in vivo investigations. Being label-free and nonperturbative, Raman spectroscopy offers intrinsic information for elucidating active biochemical processes at subcellular level. This review summarizes recent applications of Raman-based techniques, including spontaneous Raman spectroscopy and imaging, coherent Raman imaging, and Raman-stable isotope probing, in contribution to the molecular understanding of the complex biological processes in the disease. In addition, this review discusses possible future directions of Raman-based technologies in cancer research.
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http://dx.doi.org/10.3390/cancers13071718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038603PMC
April 2021

Design, synthesis and biological evaluation of 1H-indazole derivatives as novel ASK1 inhibitors.

Eur J Med Chem 2021 Aug 20;220:113482. Epub 2021 Apr 20.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, PR China; School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, PR China. Electronic address:

Apoptosis signal-regulating kinase 1 (ASK1, MAP3K5), a member of the mitogen-activated protein kinase (MAPK) signaling pathway, is involved in cell survival, differentiation, stress response, and apoptosis. ASK1 kinase inhibition has emerged as a promising therapeutic strategy for inflammatory disease. A series of novel ASK1 inhibitors with 1H-indazole scaffold were designed, synthesized and evaluated for their ASK1 kinase activity and AP1-HEK293 cell inhibitory effect. Systematic structure-activity relationship (SAR) efforts led to the discovery of promising compound 15, which showed excellent in vitro ASK1 kinase activity and potent inhibitory effects on ASK1 in AP1-HEK293 cells. In a tumor necrosis factor-α (TNF-α)-induced HT-29 intestinal epithelial cell model, compound 15 exhibited a significantly protective effect on cell viability comparable to that of GS-4997; moreover, compound 15 exhibited no obvious cytotoxicity against HT-29 cells at concentrations up to 25 μM. Mechanistic research demonstrated that compound 15 suppresses phosphorylation in the ASK1-p38/JNK signaling pathway in HT-29 cells, and regulates the expression levels of apoptosis-related proteins. Altogether, these results show that compound 15 may serve as a potential candidate compound for the treatment of inflammatory bowel disease (IBD).
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http://dx.doi.org/10.1016/j.ejmech.2021.113482DOI Listing
August 2021

Dynamic reprogramming and function of RNA N-methyladenosine modification during porcine early embryonic development.

Zygote 2021 Apr 23:1-10. Epub 2021 Apr 23.

Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China.

N6-Methyladenosine (m6A) regulates oocyte-to-embryo transition and the reprogramming of somatic cells into induced pluripotent stem cells. However, the role of m6A methylation in porcine early embryonic development and its reprogramming characteristics in somatic cell nuclear transfer (SCNT) embryos are yet to be known. Here, we showed that m6A methylation was essential for normal early embryonic development and its aberrant reprogramming in SCNT embryos. We identified a persistent occurrence of m6A methylation in embryos between 1-cell to blastocyst stages and m6A levels abruptly increased during the morula-to-blastocyst transition. Cycloleucine (methylation inhibitor, 20 mM) treatment efficiently reduced m6A levels, significantly decreased the rates of 4-cell embryos and blastocysts, and disrupted normal lineage allocation. Moreover, cycloleucine treatment also led to higher levels in both apoptosis and autophagy in blastocysts. Furthermore, m6A levels in SCNT embryos at the 4-cell and 8-cell stages were significantly lower than that in parthenogenetic activation (PA) embryos, suggesting an abnormal reprogramming of m6A methylation in SCNT embryos. Correspondingly, expression levels of m6A writers (METTL3 and METTL14) and eraser (FTO) were apparently higher in SCNT 8-cell embryos compared with their PA counterparts. Taken together, these results indicated that aberrant nuclear transfer-mediated reprogramming of m6A methylation was involved in regulating porcine early embryonic development.
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http://dx.doi.org/10.1017/S0967199420000799DOI Listing
April 2021

Discovery of a novel covalent CDK4/6 inhibitor based on palbociclib scaffold.

Eur J Med Chem 2021 Jul 3;219:113432. Epub 2021 Apr 3.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address:

Cyclin-dependent kinases 4 and 6 (CDK4/6), which are involved in dynamic regulation of cell cycle, play an indispensable role in controlling the tumor growth. Here, based on the scaffold of palbociclib, we designed and synthesized a series of covalent CDK4/6 inhibitors that targeted amino acid Thr107. The optimized compound C-13 exhibited potent in vitro anticancer activity against CDK4/6 with high selectivity over CDK4/6. Moreover, C-13 showed significant tumor growth inhibition in MDA-MB-231 tumor xenograft model (TGI of 93.49% at dose of 40 mg/kg) without causing significant weight loss and toxicity during the treatment period.
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http://dx.doi.org/10.1016/j.ejmech.2021.113432DOI Listing
July 2021

Harvesting of Rhodotorula glutinis via Polyaluminum Chloride or Cationic Polyacrylamide Using the Extended DLVO Theory.

Appl Biochem Biotechnol 2021 Apr 8. Epub 2021 Apr 8.

Beijing Key Lab of Bioprocess, National Energy R&D Center for Biorefinery, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, People's Republic of China.

Polyaluminum chloride (PAC) and cationic polyacrylamide (CPAM) play a crucial role for separating microorganisms from bulk media. However, the mechanism of adsorption between cells and flocculants remain to be further defined to improve the flocculation efficiency (FE) in extreme conditions. This study conducted the flocculation process of Rhodotorula glutinis induced by PAC and CPAM, firstly. The result demonstrated that CPAM possessed more efficient harvesting ability for R. glutinis compared to PAC. The difference of flocculation capacity was then thermodynamically explained by the extended DLVO (eDLVO) theory; it turned out that the poor harvesting efficiency of PAC was attributed to lacking of binding sites as well as low adsorption force within particles. Based on this, the FE of PAC to R. glutinis was mechanically enhanced to 99.84% from 32.89% with 0.2 g/L CPAM modification at an optimum pH of 9. Also, the paper will play a guiding role in the treatment of inorganic salt ions and organic matters in wastewater.
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http://dx.doi.org/10.1007/s12010-021-03549-1DOI Listing
April 2021

Coriander Genomics Database: a genomic, transcriptomic, and metabolic database for coriander.

Hortic Res 2020 Apr 1;7(1):55. Epub 2020 Apr 1.

Center for Genomics and Biocomputing/College of Life Sciences, North China University of Science and Technology, Tangshan, Hebei, 063210, China.

Coriander (Coriandrum sativum L.), also known as cilantro, is a globally important vegetable and spice crop. Its genome and that of carrot are models for studying the evolution of the Apiaceae family. Here, we developed the Coriander Genomics Database (CGDB, http://cgdb.bio2db.com/) to collect, store, and integrate the genomic, transcriptomic, metabolic, functional annotation, and repeat sequence data of coriander and carrot to serve as a central online platform for Apiaceae and other related plants. Using these data sets in the CGDB, we intriguingly found that seven transcription factor (TF) families showed significantly greater numbers of members in the coriander genome than in the carrot genome. The highest ratio of the numbers of MADS TFs between coriander and carrot reached 3.15, followed by those for tubby protein (TUB) and heat shock factors. As a demonstration of CGDB applications, we identified 17 TUB family genes and conducted systematic comparative and evolutionary analyses. RNA-seq data deposited in the CGDB also suggest dose compensation effects of gene expression in coriander. CGDB allows bulk downloading, significance searches, genome browser analyses, and BLAST searches for comparisons between coriander and other plants regarding genomics, gene families, gene collinearity, gene expression, and the metabolome. A detailed user manual and contact information are also available to provide support to the scientific research community and address scientific questions. CGDB will be continuously updated, and new data will be integrated for comparative and functional genomic analysis in Apiaceae and other related plants.
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http://dx.doi.org/10.1038/s41438-020-0261-0DOI Listing
April 2020

Strategies to improve the adsorption properties of graphene-based adsorbent towards heavy metal ions and their compound pollutants: A review.

J Hazard Mater 2021 08 19;415:125690. Epub 2021 Mar 19.

School of Environment and Energy, South China University of Technology, Guangzhou 510006, China.

Heavy metal-containing wastewater can be treated by adsorption technology to obtain ultra-low concentration or high-quality treated effluent. Due to the constraints of the specific surface area, surface electrical structure and spatial effect of conventional adsorbents, it is often difficult to obtain adsorbents within high adsorption capacity. Graphene has characteristics of large specific surface area, small particle size, and high adsorption efficiency. It is considered as one of the research hotspots in recent years. However, despite graphene's unique properties, graphene-based adsorbents still have some drawbacks, i.e. graphene nanosheets are easier to be stacked with each other via π-π stacking and van der Waals interactions, which affect the site exposure, impede the rapid mass transport and limit its adsorption performance. Special strategy is needed to overcome its drawbacks. This work summarizes recent literatures on utilization of three strategies-surface functionalization regulation, morphology and structure control and material composite, to improve the adsorption properties of graphene-based adsorbent towards heavy metal removal. A brief summary, perspective on strategies to improving adsorption properties of graphene-based materials for heavy metal adsorption are also presented. Certainly, this review will be useful for designing and manufacturing of graphene-based nanomaterials for water treatment.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125690DOI Listing
August 2021

Neurological deterioration as a result of improper neck position detected by intraoperative neurophysiological monitoring in a cervical stenosis patient: A case report.

Medicine (Baltimore) 2021 Mar;100(11):e24241

Department of Spine Surgery, The Second Hospital of Jilin University.

Rationale: Intraoperative neurophysiological monitoring (IONM) is widely used in spinal surgeries to prevent iatrogenic spinal cord injury (SCI). Most surgeons focus on avoiding neurological compromise intraoperatively, while ignoring the possibility of nerve damage preoperatively, such as neck positioning. Thus, this study aims to report a case with transient neurological deterioration due to improper neck position detected by IONM during cervical surgery.

Patient Concerns: A 63-year-old male patient had been suffering from hypoesthesia of the upper and lower extremities for three years.

Diagnoses: Severe cervical stenosis (C5-C7) and cervical ossification of a posterior longitudinal ligament.

Interventions: The cervical stenosis patient underwent an anterior cervical corpectomy decompression and fusion (ACDF) surgery with the assistance of IONM. When the lesion segment was exposed, the SSEP and MEP suddenly elicited difficulty indicating that the patient may have developed SCI. All the technical causes of IONM events were eliminated, and the surgeon suspended operation immediately and suspected that the IONM alerts were caused by cervical SCI due to the improper position of the neck. Subsequently, the surgeon repositioned the neck of the patient by using a thinner shoulders pad.

Outcomes: At the end of the operation, the MEP and SSEP signals gradually returned to 75% and 80% of the baseline, respectively. Postoperatively, the muscle strength of bilateral biceps decreased from grade IV to grade III. Besides, the sensory disturbance of both upper extremities aggravated. However, the muscle power and hypoesthesia were significantly improved after three months of neurotrophic therapy and rehabilitation training, and no complications of nerve injury were found at the last follow-up visit.

Lessons: IONM, consisting of SSEP and MEP, should be applied throughout ACDF surgery from the neck positioning to suture incisions. Besides, in the ward 1to 2 days before operation, it is necessary for conscious patients with severe cervical stenosis to simulate the intraoperative neck position. If the conscious patients present signs of nerve damage, they can adjust the neck position immediately until the neurological symptoms relieve. Therefore, intraoperatively, the unconscious patient can be placed in a neck position that was confirmed preoperatively to prevent SCI.
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http://dx.doi.org/10.1097/MD.0000000000024241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982153PMC
March 2021

Zina percutaneous screw fixation combined with endoscopic lumbar intervertebral fusion under intraoperative neuromonitoring: A case report.

Medicine (Baltimore) 2021 Mar;100(11):e24220

Department of Orthopaedics, The Second Hospital of Jilin University, Changchun, Jilin Province, China.

Introduction: Traditional open discectomy and intervertebral fusion surgery is the common strategy for lumbar disc herniation (LDH). However, it has the disadvantages of long recovery time and severe paravertebral soft tissue injury. Zina percutaneous screw fixation combined with endoscopic lumbar intervertebral fusion (ZELIF), as a novel minimally invasive surgical technique for LDH, has the advantages in quicker recovery, less soft tissue destruction, shorter hospital stays and less pain. We report a novel technique of ZELIF under intraoperative neuromonitoring (INM) for the treatment of LDH.

Patient Concerns: A 51-year-old male presented to our hospital with left lower extremity pain and numbness for 1 year.

Diagnosis: Lumbar disc herniation (LDH).

Interventions: This patient was treated with Zina percutaneous screw fixation combined with endoscopic neural decompression, endplate preparation, and intervertebral fusion through Kambin's triangle. Each step of the operation was performed under INM.

Outcomes: The follow-up period lasted 12 months; the hospitalization lasted 4 nights; the blood loss volume was 65 ml, and the time of operation was 266 min. INM showed no neurological damage during the surgery. No surgical complications, including neurological deterioration, cage migration, non-union, instrumentation failure or revision operation, were observed during the follow-up period. Visual Analogue Scale (VAS) score reduced from 7 to 1; the Oswestry Disability Index (ODI) decreased from 43 to 14; the EQ-5D score was 10 preoperatively and 15 at the final follow-up visit; the Physical Component Summary of the 36-Item Short Form Health Survey (SF-36) was 48 preoperatively and 49 at the last follow up visit; the SF-36 Mental Component Summary was 47 before surgery and decreased to 41 postoperatively.

Conclusion: ZELIF under INM may represent a feasible, safe and effective alternative to endoscopic intervertebral fusion and percutaneous screw fixation, for decompressing the lumbar's exiting nerve root directly with minimal invasion in selected patients.
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http://dx.doi.org/10.1097/MD.0000000000024220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982225PMC
March 2021

Hepatitis B virus X protein promotes vimentin expression via LIM and SH3 domain protein 1 to facilitate epithelial-mesenchymal transition and hepatocarcinogenesis.

Cell Commun Signal 2021 Mar 15;19(1):33. Epub 2021 Mar 15.

Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China.

Background: Hepatitis B virus (HBV) X protein (HBX) has been reported to be responsible for the epithelial-mesenchymal transition (EMT) in HBV-related hepatocellular carcinoma (HCC). Vimentin is an EMT-related molecular marker. However, the importance of vimentin in the pathogenesis of HCC mediated by HBX has not been well determined.

Methods: The expression of vimentin induced by HBX, and the role of LIM and SH3 domain protein 1 (LASP1) in HBX-induced vimentin expression in hepatoma cells were examined by western blot and immunohistochemistry analysis. Both the signal pathways involved in the expression of vimentin, the interaction of HBX with vimentin and LASP1, and the stability of vimentin mediated by LASP1 in HBX-positive cells were assessed by western blot, Co-immunoprecipitation, and GST-pull down assay. The role of vimentin in EMT, proliferation, and migration of HCC cells mediated by HBX and LASP1 were explored with western blot, CCK-8 assay, plate clone formation assay, transwell assay, and wound healing assay.

Results: Vimentin expression was increased in both HBX-positive hepatoma cells and HBV-related HCC tissues, and the expression of vimentin was correlated with HBX in HBV-related HCC tissues. Functionally, vimentin was contributed to the EMT, proliferation, and migration of hepatoma cells mediated by HBX. The mechanistic analysis suggested that HBX was able to enhance the expression of vimentin through LASP1. On the one hand, PI3-K, ERK, and STAT3 signal pathways were involved in the upregulation of vimentin mediated by LASP1 in HBX-positive hepatoma cells. On the other hand, HBX could directly interact with vimentin and LASP1, and dependent on LASP1, HBX was capable of promoting the stability of vimentin via protecting it from ubiquitination mediated protein degradation. Besides these, vimentin was involved in the growth and migration of hepatoma cells mediated by LASP1 in HBX-positive hepatoma cells.

Conclusion: Taken together, these findings demonstrate that, dependent on LASP1, vimentin is crucial for HBX-mediated EMT and hepatocarcinogenesis, and may serve as a potential target for HBV-related HCC treatment. Video abstract.
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http://dx.doi.org/10.1186/s12964-021-00714-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958410PMC
March 2021

Newcastle Disease Virus Inhibits the Proliferation of T Cells Induced by Dendritic Cells and .

Front Immunol 2020 23;11:619829. Epub 2021 Feb 23.

College of Veterinary Medicine, College of Animal Science, Jilin University, Changchun, China.

Newcastle disease virus (NDV) infects poultry and antagonizes host immunity several mechanisms. Dendritic cells (DCs) are characterized as specialized antigen presenting cells, bridging innate and adaptive immunity and regulating host resistance to viral invasion. However, there is little specific knowledge of the role of DCs in NDV infection. In this study, the representative NDV lentogenic strain LaSota was used to explore whether murine bone marrow derived DCs mature following infection. We examined surface molecule expression and cytokine release from DCs as well as proliferation and activation of T cells and in the context of NDV. The results demonstrated that infection with lentogenic strain LaSota induced a phenotypic maturation of immature DCs (imDCs), which actually led to curtailed T cell responses. Upon infection, the phenotypic maturation of DCs was reflected by markedly enhanced MHC and costimulatory molecule expression and secretion of proinflammatory cytokines. Nevertheless, NDV-infected DCs produced the anti-inflammatory cytokine IL-10 and attenuated T cell proliferation, inducing Th2-biased responses. Therefore, our study reveals a novel understanding that DCs are phenotypically mature but dysfunctional in priming T cell responses during NDV infection.
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http://dx.doi.org/10.3389/fimmu.2020.619829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942023PMC
February 2021

Delayed rise of oral fluid antibodies, elevated BMI, and absence of early fever correlate with longer time to SARS-CoV-2 RNA clearance in an longitudinally sampled cohort of COVID-19 outpatients.

medRxiv 2021 Mar 3. Epub 2021 Mar 3.

Background: Sustained molecular detection of SARS-CoV-2 RNA in the upper respiratory tract (URT) in mild to moderate COVID-19 is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection.

Methods: Ninety-five outpatients self-collected mid-turbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models.

Results: Viral RNA clearance, as measured by SARS-CoV-2 RT-PCR, in 507 URT samples occurred a median (IQR) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR positive samples tested. All participants but one with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (aHR 0.96, 95% CI 0.92-0.99, p=0.020) and BMI ≥ 25kg/m (aHR 0.37, 95% CI 0.18-0.78, p=0.009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as one of first three COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR 2.06, 95% CI 1.02-4.18, p=0.044).

Conclusions: We demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.
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http://dx.doi.org/10.1101/2021.03.02.21252420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941665PMC
March 2021

Protective effects of oridonin against cerebral ischemia/reperfusion injury by inhibiting the NLRP3 inflammasome activation.

Tissue Cell 2021 Feb 24;71:101514. Epub 2021 Feb 24.

Department of Neurology, Tianjin Medical University General Hospital, Tianjin, 300052, People's Republic of China. Electronic address:

NOD-like receptor protein 3 (NLRP3) inflammasome is tightly related to the pathogenesis of cerebral ischemia/reperfusion (I/R) injury, and oridonin (Ori) has shown the potential to alleviate ischemia/reperfusion injury with underlying mechanisms. Our study aims to figure out whether Ori protects against the cerebral ischemia/reperfusion injury by the NLRP3 inflammasome signaling. In this study, a temporary middle cerebral artery occlusion (MCAO) and reperfusion surgery was conducted on male C57BL/6 mice to mimic cerebral I/R injury in vivo. Cellular model of cerebral I/R in vitro was achieved by oxygen-glucose deprivation and reintroduction (OGD/R) in BV2 microglia cells. We found that Ori treatment significantly relieved the neurological deficits, neuronal injury and microglia activation in I/R mice according to morphological and histological analyses. Meanwhile, the inactivation of NLRP3 inflammasome was determined in Ori-treated mice with significantly down-regulated expressions of inflammasome-related genes. Western-blot analysis further demonstrated the negative effect of Ori on NF-κB signaling with diminished phosphorylation and degradation of IκBα as well as suppressed translocation of p65. Furthermore, we indicated that Ori suppressed the activation of NLRP3 inflammasome in OGD/R induced BV2 microglia cells by inhibiting NF-κB signaling. In summary, our findings make Ori a potential candidate for therapy of cerebral I/R injury in the future.
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http://dx.doi.org/10.1016/j.tice.2021.101514DOI Listing
February 2021

Anisotropic Janus SiP Monolayer as a Photocatalyst for Water Splitting.

J Phys Chem Lett 2021 Mar 4;12(9):2464-2470. Epub 2021 Mar 4.

Physical Science and Engineering Division (PSE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.

The design of materials meeting the rigorous requirements of photocatalytic water splitting is still a challenge. Anisotropic Janus 2D materials exhibit great potential due to outstandingly high photocatalytic efficiency. Unfortunately, these materials are scarce. By means of ab initio swarm-intelligence search calculations, we identify a SiP monolayer with Janus structure (i.e., out-of-plane asymmetry). The material turns out to be semiconducting with an indirect band gap of 2.39 eV enclosing the redox potentials of water. Notably, the oxygen and hydrogen evolution half reactions can happen simultaneously at the Si and P atoms, respectively, driven merely by the radiation-induced electrons and holes. The carrier mobility is found to be anisotropic and high, up to 10 cm V s, facilitating fast transport of the photogenerated carriers. The SiP monolayer shows remarkably strong optical absorption in the visible-to-ultraviolet range of the solar spectrum, ensuring efficient utilization of the solar energy.
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http://dx.doi.org/10.1021/acs.jpclett.0c03841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041313PMC
March 2021

Comparative analysis of long noncoding RNAs in angiosperms and characterization of long noncoding RNAs in response to heat stress in Chinese cabbage.

Hortic Res 2021 Mar 1;8(1):48. Epub 2021 Mar 1.

College of Life Sciences/Center for Genomics and Bio-computing, North China University of Science and Technology, Tangshan, Hebei, China.

Long noncoding RNAs (lncRNAs) are widely present in different species and play critical roles in response to abiotic stresses. However, the functions of lncRNAs in Chinese cabbage under heat stress remain unknown. Here, we first conducted a global comparative analysis of 247,242 lncRNAs among 37 species. The results indicated that lncRNAs were poorly conserved among different species, and only 960 lncRNAs were homologous to 524 miRNA precursors. We then carried out lncRNA sequencing for a genome-wide analysis of lncRNAs and their target genes in Chinese cabbage at different stages of heat treatment. In total, 18,253 lncRNAs were identified, of which 1229 differentially expressed (DE) lncRNAs were characterized as being heat-responsive. The ceRNA network revealed that 38 lncRNAs, 16 miRNAs, and 167 mRNAs were involved in the heat response in Chinese cabbage. Combined analysis of the cis- and trans-regulated genes indicated that the targets of DE lncRNAs were significantly enriched in the "protein processing in endoplasmic reticulum" and "plant hormone signal transduction" pathways. Furthermore, the majority of HSP and PYL genes involved in these two pathways exhibited similar expression patterns and responded to heat stress rapidly. Based on the networks of DE lncRNA-mRNAs, 29 and 22 lncRNAs were found to interact with HSP and PYL genes, respectively. Finally, the expression of several critical lncRNAs and their targets was verified by qRT-PCR. Overall, we conducted a comparative analysis of lncRNAs among 37 species and performed a comprehensive analysis of lncRNAs in Chinese cabbage. Our findings expand the knowledge of lncRNAs involved in the heat stress response in Chinese cabbage, and the identified lncRNAs provide an abundance of resources for future comparative and functional studies.
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http://dx.doi.org/10.1038/s41438-021-00484-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917108PMC
March 2021

Nuclear TEAD4 with SIX1 Overexpression is an Independent Prognostic Marker in the Stage I-III Colorectal Cancer.

Cancer Manag Res 2021 17;13:1581-1589. Epub 2021 Feb 17.

Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Introduction: Stage I-III colorectal cancer patients are under risk of tumor recurrence and metachronous metastasis after radical surgery. An increased expression of transcription factor TEAD4 is associated with epithelial-mesenchymal transition, metastasis and poor prognosis in colorectal cancer. However, the mechanistic role of TEAD4 in driving colon cancer progression and its prognostic value in early stage of CRC remains unclear.

Methods: In this study, the regulation, function and prognostic significance of TEAD4 and its new direct target gene SIX1 in CRC progression were evaluated using human tissues, molecular and cell biology.

Results: We show that TEAD4 directly upregulates the expression of SIX1 at transcriptional level in CRC cells, establishing that SIX1 is a new direct target gene of TEAD4. TEAD4 promotes EMT and cell migration of CRC cells, while SIX1 knockdown attenuates this effect and SIX1 overexpression enhances this effect, indicating that SIX1 mediates the function of TEAD4 in promoting cell migration in CRC cells. Clinically, nuclear TEAD4, overexpression of SIX1 and nuclear TEAD4 with SIX1 overexpression predict poor prognosis in CRC patients.

Discussion: Our study identifies TEAD4-SIX1-CDH1 form a novel signaling axis, which contributes to CRC progression, and its aberrant expression and activation predicts poor prognostic for CRC patients in stage I-III.
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http://dx.doi.org/10.2147/CMAR.S260790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898202PMC
February 2021

Self-Collected Oral Fluid Saliva Is Insensitive Compared With Nasal-Oropharyngeal Swabs in the Detection of Severe Acute Respiratory Syndrome Coronavirus 2 in Outpatients.

Open Forum Infect Dis 2021 Feb 30;8(2):ofaa648. Epub 2020 Dec 30.

Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic control will require widespread access to accurate diagnostics. Salivary sampling circumvents swab supply chain bottlenecks, is amenable to self-collection, and is less likely to create an aerosol during collection compared with the nasopharyngeal swab.

Methods: We compared real-time reverse-transcription polymerase chain reaction Abbott m2000 results from matched salivary oral fluid (gingival crevicular fluid collected in an Oracol device) and nasal-oropharyngeal (OP) self-collected specimens in viral transport media from a nonhospitalized, ambulatory cohort of coronavirus disease 2019 (COVID-19) patients at multiple time points. These 2 sentences should be at the beginning of the results.

Results: There were 171 matched specimen pairs. Compared with nasal-OP swabs, 41.6% of the oral fluid samples were positive. Adding spit to the oral fluid percent collection device increased the percent positive agreement from 37.2% (16 of 43) to 44.6% (29 of 65). The positive percent agreement was highest in the first 5 days after symptoms and decreased thereafter. All of the infectious nasal-OP samples (culture positive on VeroE6 TMPRSS2 cells) had a matched SARS-CoV-2 positive oral fluid sample.

Conclusions: In this study of nonhospitalized SARS-CoV-2-infected persons, we demonstrate lower diagnostic sensitivity of self-collected oral fluid compared with nasal-OP specimens, a difference that was especially prominent more than 5 days from symptom onset. These data do not justify the routine use of oral fluid collection for diagnosis of SARS-CoV-2 despite the greater ease of collection. It also underscores the importance of considering the method of saliva specimen collection and the time from symptom onset especially in outpatient populations.
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http://dx.doi.org/10.1093/ofid/ofaa648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798743PMC
February 2021

Brassica carinata genome characterization clarifies U's triangle model of evolution and polyploidy in Brassica.

Plant Physiol 2021 Feb 4. Epub 2021 Feb 4.

Laboratory of Germplasm Innovation and Molecular Breeding, Institute of Vegetable Science, Zhejiang University, Hangzhou 310058, China.

Ethiopian mustard (Brassica carinata) in the Brassicaceae family possesses many excellent agronomic traits. Here, the high-quality genome sequence of B. carinata is reported. Characterization revealed a genome anchored to 17 chromosomes with a total length of 1.087 Gb and an N50 scaffold length of 60 Mb. Repetitive sequences account for approximately 634 Mb or 58.34% of the B. carinata genome. Notably, 51.91% of 97,149 genes are confined to the terminal 20% of chromosomes as a result of the expansion of repeats in pericentromeric regions. Brassica carinata shares one whole-genome triplication event with the five other species in U's triangle, a classic model of evolution and polyploidy in Brassica. Brassica carinata was deduced to have formed ∼0.047 Mya, which is slightly earlier than B. napus but later than B. juncea. Our analysis indicated that the relationship between the two subgenomes (BcaB and BcaC) is greater than that between other two tetraploid subgenomes (BjuB and BnaC) and their respective diploid parents. RNA-seq datasets and comparative genomic analysis were used to identify several key genes in pathways regulating disease resistance and glucosinolate metabolism. Further analyses revealed that genome triplication and tandem duplication played important roles in the expansion of those genes in Brassica species. With the genome sequencing of B. carinata completed, the genomes of all six Brassica species in U's triangle are now resolved. The data obtained from genome sequencing, transcriptome analysis, and comparative genomic efforts in this study provide valuable insights into the genome evolution of the six Brassica species in U's triangle.
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http://dx.doi.org/10.1093/plphys/kiab048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154070PMC
February 2021