Publications by authors named "Tingting Yu"

275 Publications

The mid-Miocene Zhangpu biota reveals an outstandingly rich rainforest biome in East Asia.

Sci Adv 2021 Apr 30;7(18). Epub 2021 Apr 30.

Division of Entomology, Natural History Museum, University of Kansas, 1501 Crestline Drive, Suite 140, Lawrence, KS 66045, USA.

During the Mid-Miocene Climatic Optimum [MMCO, ~14 to 17 million years (Ma) ago], global temperatures were similar to predicted temperatures for the coming century. Limited megathermal paleoclimatic and fossil data are known from this period, despite its potential as an analog for future climate conditions. Here, we report a rich middle Miocene rainforest biome, the Zhangpu biota (~14.7 Ma ago), based on material preserved in amber and associated sedimentary rocks from southeastern China. The record shows that the mid-Miocene rainforest reached at least 24.2°N and was more widespread than previously estimated. Our results not only highlight the role of tropical rainforests acting as evolutionary museums for biodiversity at the generic level but also suggest that the MMCO probably strongly shaped the East Asian biota via the northern expansion of the megathermal rainforest biome. The Zhangpu biota provides an ideal snapshot for biodiversity redistribution during global warming.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abg0625DOI Listing
April 2021

LncRNA MNX1-AS1 drives aggressive laryngeal squamous cell carcinoma progression and serves as a ceRNA to target FoxM1 by sponging microRNA-370.

Aging (Albany NY) 2021 Mar 19;13(7):9900-9910. Epub 2021 Mar 19.

Department of Otolaryngology-Head and Neck Surgery, The First Hospital of Jilin University, Changchun 130021, China.

Long non-coding RNA (LncRNA) MNX1 antisense RNA 1(MNX1-AS1) is associated with the pathology of numerous cancers. But, the role and underlying pathways of MNX1-AS1 in the regulation of laryngeal squamous cell carcinoma (LSCC) is not known. We demonstrated remarkably elevated levels of MNX1-AS1 in the LSCC tissues, which was correlated with poor disease prognosis. Moreover, MNX1-AS1-silencing strongly suppressed LSCC cell proliferation, migration, and invasion. We also demonstrated that MNX1-AS1 sequesters that activity of miR-370, thereby releasing Forkhead Box ml (FoxM1) from the inhibitory actions of MNX1-AS1. Furthermore, the positive correlation of MNX1-AS1 and FoxM1 as well as the converse correlation between miR-370 and MNX1-AS1 (or FoxM1) were revealed in LSCC tissues using experiments. Based on rescue assays, FoxM1 overexpression or miR-370 downregulation partially recovered the inhibitory effect of MNX1-AS1 silencing on LSCC cells. Moreover, knockdown of MNX1-AS1 retarded tumor growth in nude mice model. In summary, these findings verified that MNX1-AS1 modulated LSCC progression by competitively binding with miR-370 to regulate FoxM1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064170PMC
March 2021

Potential targets identified in adenoid cystic carcinoma point out new directions for further research.

Am J Transl Res 2021 15;13(3):1085-1108. Epub 2021 Mar 15.

Department of Oral and Maxillofacial Surgery, Jinan Stomatological Hospital Jinan, China.

Adenoid cystic carcinoma (AdCC) of the head and neck originates from salivary glands, with high risks of recurrence and metastasis that account for the poor prognosis of patients. The purpose of this research was to identify key genes related to AdCC for further investigation of their diagnostic and prognostic significance. In our study, the AdCC sample datasets GSE36820, GSE59702 and GSE88804 from the Gene Expression Omnibus (GEO) database were used to explore the abnormal coexpression of genes in AdCC compared with their expression in normal tissue. A total of 115 DEGs were obtained by screening with GEO2R and FunRich software. According to functional annotation analysis using Enrichr, these DEGs were mainly enriched in the SOX2, AR, SMAD and MAPK signaling pathways. A protein-protein network of the DEGs was established by the Search Tool for the Retrieval of Interacting Genes (STRING) and annotated through the WEB-based Gene SeT AnaLysis Toolkit (WebGestalt) and was shown to be enriched with proteins involved in cardiac muscle cell proliferation and extracellular matrix organization. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that ITGA9, LAMB1 and BAMBI were associated with the PI3K-Akt and TGF-β pathways. Furthermore, 36 potential target miRNAs were identified by the OncomiR and miRNA Pathway Dictionary Database (miRPathDB). In conclusion, SLC22A3, FOXP2, Cdc42EP3, COL27A1, DUSP1 and HSPB8 played critical roles according to the enrichment analysis; ITGA9, LAMB1 and BAMBI were involved in significant pathways according to the KEGG analysis; ST3Gal4 is a pivotal component of the PPI network of all the DEGs obtained; SPARC, COL4A2 and PRELP were highly related to multiple malignancies in pan-cancer research; hsa-miR-29-3p, hsa-miR-132-3p and hsa-miR-708-5p were potential regulators in AdCC. The involved pathways, biological processes and miRNAs have been shown to play significant roles in the genesis, growth, invasion and metastasis of AdCC. In this study, these identified DEGs were considered to have a potential influence on AdCC but have not been studied in this disease. The analysis results promote our understanding of the molecular mechanisms and biological processes of AdCC, which might be useful for targeted therapy or diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014416PMC
March 2021

Zebrafish Mutants Display Osteoclast Over-Activation and Bone Deformity Resembling Osteolysis in MCTO Patients.

Biomolecules 2021 Mar 23;11(3). Epub 2021 Mar 23.

Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

Multicentric carpotarsal osteolysis (MCTO) is a rare skeletal dysplasia with osteolysis at the carpal and tarsal bones. Heterozygous missense mutations in the transcription factor MAFB are found in patients with MCTO. MAFB is reported to negatively regulate osteoclastogenesis in vitro. However, the in vivo function of MAFB and its relation to MCTO remains unknown. In this study, we generated zebrafish MAFB homolog mutant utilizing CRISPR/Cas9 technology. deficient zebrafish demonstrated enhanced osteoclast cell differentiation and abnormal cartilage and bone development resembling MCTO patients. It is known that osteoclasts are hematopoietic cells derived from macrophages. Loss of caused selective expansion of definitive macrophages and myeloid cells, supporting that restricts myeloid differentiation in vivo. We also demonstrate that MAFB MCTO mutations failed to rescue the defective osteoclastogenesis in embryos, but did not affect osteoclast cells in wild type embryos. The mechanism of MCTO mutations is likely haploinsufficiency. Zebrafish mutant provides a useful model to study the function of MAFB in osteoclastogenesis and the related MCTO disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom11030480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004647PMC
March 2021

RNA methylation in hematological malignancies and its interactions with other epigenetic modifications.

Leukemia 2021 Mar 25. Epub 2021 Mar 25.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Hematological malignancies are a class of malignant neoplasms attributed to abnormal differentiation of hematopoietic stem cells (HSCs). The systemic involvement, poor prognosis, chemotherapy resistance, and recurrence common in hematological malignancies urge researchers to look for novel treatment targets and mechanisms. In recent years, epigenetic abnormalities have been shown to play a vital role in tumorigenesis and progression in hematological malignancies. In addition to DNA methylation and histone modifications, which are most studied, RNA methylation has become increasingly significant. In this review, we elaborate recent advances in the understanding of RNA modification in the pathogenesis, diagnosis and molecular targeted therapies of hematological malignancies and discuss its intricate interactions with other epigenetic modifications, including DNA methylation, histone modifications and noncoding RNAs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-021-01225-1DOI Listing
March 2021

Physical and chemical mechanisms of tissue optical clearing.

iScience 2021 Mar 12;24(3):102178. Epub 2021 Feb 12.

Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.

Advanced optical methods combined with various probes pave the way toward molecular imaging within living cells. However, major challenges are associated with the need to enhance the imaging resolution even further to the subcellular level for the imaging of larger tissues, as well as for studies. High scattering and absorption of opaque tissues limit the penetration of light into deep tissues and thus the optical imaging depth. Tissue optical clearing technique provides an innovative way to perform deep-tissue imaging. Recently, various optical clearing methods have been developed, which provide tissue clearing based on similar physical principles via different chemical approaches. Here, we introduce the mechanisms of the current clearing methods from fundamental physical and chemical perspectives, including the main physical principle, refractive index matching via various chemical approaches, such as dissociation of collagen, delipidation, decalcification, dehydration, and hyperhydration, to reduce scattering, as well as decolorization to reduce absorption.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.isci.2021.102178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920833PMC
March 2021

Whole-Genome Re-sequencing and Transcriptome Reveal Oogenesis-Related Genes in Autotetraploid Carassius auratus.

Mar Biotechnol (NY) 2021 Apr 6;23(2):233-241. Epub 2021 Mar 6.

State Key Laboratory of Developmental Biology of Freshwater Fish, Engineering Research Center of Polyploid Fish Reproduction and Breeding of the State Education Ministry, College of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, People's Republic of China.

Oogenesis involves a series of biochemical and physiological transformations and numerous regulated genes. The autotetraploid Carassius auratus (4nRR) originated from whole-genome duplication of Carassius auratus red var. (RCC), which produces diploid eggs through pairing of diploid-like chromosome during female meiosis. To explore the molecular mechanisms underlying oogenesis in 4nRR, we used the Illumina sequencing platform to characterize the ovaries of 4nRR and RCC. Transcriptome and whole-genome re-sequencing were performed to uncover the key genes and potential genetic mutations related to oogenesis. Each sample produced paired-end reads in the range of 66.97 to 98.36 million via Illumina HiSeq™ 2500. After comparing of the transcriptome profiles between the 4nRR and RCC, we uncovered 8562 differentially expressed genes (DEGs). The DEGs were enriched in oogenesis-related processes, including oogenesis, oocyte development, ubiquitin-mediated proteolysis, the signaling pathways of MAPK and calcium, and oocyte meiosis as investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Additionally, whole-genome re-sequencing revealed 34,058,834 SNPs and 6,153,711 InDels, including 6,677,638 non-synonymous variations (SNPs) and 706,210 frame-shift InDels in the 8510 DEGs of 4nRR fish. Subsequently, whole-genome re-sequencing and transcriptomatic analyses revealed the genes that participate in oogenesis associated processes. Specifically, genes involved in ubiquitin-mediated proteolysis (SMURF1, UBE2I), calcium transport (CALM3, CAMK4), and meiosis (MAPK3, GRB2, CPEB1, CCNB2, YWHAE) were related to oogenesis in 4nRR. These findings enrich our understanding of oogenesis in the autopolyploid fish.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10126-021-10018-7DOI Listing
April 2021

Lycorine inhibits cell proliferation, migration and invasion, and primarily exerts cytostatic effects in human colorectal cancer via activating the ROS/p38 and AKT signaling pathways.

Oncol Rep 2021 04 2;45(4). Epub 2021 Mar 2.

Key Laboratory of Clinical Laboratory Medical Diagnostics, Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.

Colorectal cancer (CRC) is a life‑threatening malignant tumor of the digestive tract. Diverse gene mutations and complicated alterations to the signaling pathways in CRC lead to heterogeneity in response to chemotherapy. Moreover, anticancer drugs for CRC chemotherapy are limited due to adverse events. Therefore, developing more effective, tolerable and safe drugs for the treatment of CRC is important. The present study aimed to investigate the effect of lycorine on human CRC cell proliferation, migration, invasion, apoptosis, cell cycle distribution, as well as the underlying molecular mechanism. The crystal violet staining and MTT assay results demonstrated that lycorine suppressed cell proliferation in a dose‑ and time‑dependent manner in the three CRC cell lines, HCT116, LoVo and SW480. Similarly, verified by performing wound healing and Transwell assays, lycorine significantly inhibited HCT116 and LoVo cell migration and invasion compared with the control group. In LoVo cells, the protein expression levels of matrix metallopeptidases, snail family transcriptional repressor 1, Vimentin and N‑cadherin were significantly downregulated, whereas the protein expression levels of E‑cadherin were significantly upregulated by lycorine treatment compared with the control group. The Hoechst 33258 staining and flow cytometry assay results indicated that lycorine mediated its cytostatic effect on CRC cells potentially via inducing cell cycle arrest, but not apoptosis. Compared with the control group, lycorine significantly induced HCT116 cell cycle arrest at the G/M phase, but significantly induced LoVo cell cycle arrest at the S and G/M phases. Furthermore, lycorine significantly downregulated the protein expression levels of cyclin D1 and cyclin E1, but significantly increased p21 and Smad4 protein expression levels in HCT116 and LoVo cells compared with the control group. The intracellular reactive oxygen species (ROS) measurement results also indicated that compared with the control group, lycorine significantly induced ROS accumulation, and increased phosphorylated‑p38 expression levels and AKT phosphorylation. Collectively, the present study suggested that lycorine might induce cell cycle arrest and exert cytostatic effects potentially via activating ROS/p38 and AKT signaling pathways in CRC cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2021.7970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879421PMC
April 2021

Soft Liver Phantom with a Hollow Biliary System.

Ann Biomed Eng 2021 Feb 16. Epub 2021 Feb 16.

Cyber Valley Research Group, Institute of Physical Chemistry, University of Stuttgart, Pfaffenwaldring 55, 70569, Stuttgart, Germany.

Hepatobiliary interventions are regarded as difficult minimally-invasive procedures that require experience and skills of physicians. To facilitate the surgical training, we develop a soft, high-fidelity and durable liver phantom with detailed morphology. The phantom is anatomically accurate and feasible for the multi-modality medical imaging, including computer tomography (CT), ultrasound, and endoscopy. The CT results show that the phantom resembles the detailed anatomy of real livers including the biliary ducts, with a spatial root mean square error (RMSE) of 1.7 ± 0.7 mm and 0.9 ± 0.2 mm for the biliary duct and the liver outer shape, respectively. The sonographic signals and the endoscopic appearance highly mimic those of the real organ. An electric sensing system was developed for the real-time quantitative tracking of the transhepatic puncturing needle. The fabrication method herein is accurate and reproducible, and the needle tracking system offers a robust and general approach to evaluate the centesis outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10439-021-02726-xDOI Listing
February 2021

Mesenchymal stem cells modified by FGF21 and GLP1 ameliorate lipid metabolism while reducing blood glucose in type 2 diabetic mice.

Stem Cell Res Ther 2021 Feb 15;12(1):133. Epub 2021 Feb 15.

Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Academy of Military Sciences, Beijing, 100850, China.

Objective: The purpose of this study was to investigate the therapeutic effects of genetically modified mesenchymal stem cells (MSCs) in the treatment of type 2 diabetes mellitus (T2DM) in order to identify a new method for treating diabetes that differs from traditional medicine and to provide a new means by which to fundamentally improve or treat diabetes.

Methods: MSCs derived from adipose tissue were modified to overexpress FGF21 and GLP1, which was achieved through lentiviral particle transduction. The cells were transplanted into BKS.Cg-Dock7m+/+Leprdb/Nju mice (T2DM mouse model). Injections of physiological saline (0.1 mL) and liraglutide (0.5 mg/kg) were used as negative and positive controls, respectively. ELISA or Western blotting was used for protein analysis, and quantitative real-time PCR was used for gene expression analysis.

Results: Genetic modification had no effects on the morphology, differentiation ability, or immunophenotype of MSCs. Moreover, MSC-FGF21+GLP1 cells exhibited significantly increased secretion of FGF21 and GLP1. In the T2DM mouse model, the transplantation of MSC-FGF21+GLP1 cells ameliorated the changes in blood glucose and weight, promoted the secretion of insulin, enhanced the recovery of liver structures, and improved the profiles of lipids. Moreover, FGF21 and GLP1 exerted synergistic effects in the regulation of glucolipid metabolism by controlling the expression of insulin, srebp1, and srebp2.

Conclusion: Stem cell treatment based on MSCs modified to overexpress the FGF21 and GLP1 genes is an effective approach for the treatment of T2DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13287-021-02205-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885588PMC
February 2021

Regulation of Gene Expression Associated With the N6-Methyladenosine (m6A) Enzyme System and Its Significance in Cancer.

Front Oncol 2020 21;10:623634. Epub 2021 Jan 21.

Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou, China.

N6-methyladenosine (m6A), an important RNA modification, is a reversible behavior catalyzed by methyltransferase complexes (m6A "writers"), demethylated transferases (m6A "erasers"), and binding proteins (m6A "readers"). It plays a vital regulatory role in biological functions, involving in a variety of physiological and pathological processes. The level of m6A will affect the RNA metabolism including the degradation of mRNA, and processing or translation of the modified RNA. Its abnormal changes will lead to disrupting the regulation of gene expression and promoting the occurrence of aberrant cell behavior. The abnormal expression of m6A enzyme system can be a crucial impact disturbing the abundance of m6A, thus affecting the expression of oncogenes or tumor suppressor genes in various types of cancer. In this review, we elucidate the special role of m6A "writers", "erasers", and "readers" in normal physiology, and how their altered expression affects the cell metabolism and promotes the occurrence of tumors. We also discuss the potential to target these enzymes for cancer diagnosis, prognosis, and the development of new therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.623634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859513PMC
January 2021

Three-dimensional cell-culture platform based on hydrogel with tunable microenvironmental properties to improve insulin-secreting function of MIN6 cells.

Biomaterials 2021 Mar 21;270:120687. Epub 2021 Jan 21.

State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, China. Electronic address:

Pancreatic β-cells have been reported to be mechanosensitive to cellular microenvironments, and subjecting the cells to more physiologically relevant microenvironments can produce better results than when subjecting them to the conventional two-dimensional (2D) cell-culture conditions. In this work, we propose a novel three-dimensional (3D) strategy for inducing multicellular spheroid formation based on hydrogels with tunable mechanical and interfacial properties. The results indicate that MIN6 cells can sense the substrates and form tightly clustered monolayers or multicellular spheroids on hydrogels with tunable physical properties. Compared to the conventional 2D cell-culture system, the glucose sensitivities of the MIN6 cells cultured in the 3D culture model is enhanced greatly and their insulin content (relative to the amount of protein) is increased 7.3-7.9 folds. Moreover, the relative gene and protein expression levels of some key factors such as Pdx1, NeuroD1, Piezo1, and Rac1 in the MIN6 cells are significantly higher on the 3D platform, compared to the 2D control group. We believe that this 3D cell-culture system developed for the generation of multicellular spheroids will be a promising platform for diabetes treatment in clinical islet transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2021.120687DOI Listing
March 2021

Discovery of thiosemicarbazone derivatives as effective New Delhi metallo--lactamase-1 (NDM-1) inhibitors against NDM-1 producing clinical isolates.

Acta Pharm Sin B 2021 Jan 16;11(1):203-221. Epub 2020 Jul 16.

State Key Laboratory of Esophageal Cancer Prevention and Treament, Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Key Laboratory of Henan Province for Drug Quality and Evaluation, Institute of Pharmaceutical Research and School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.

New Delhi metallo--lactamase-1 (NDM-1) is capable of hydrolyzing nearly all -lactam antibiotics, posing an emerging threat to public health. There are currently less effective treatment options for treating NDM-1 positive "superbug", and no promising NDM-1 inhibitors were used in clinical practice. In this study, structure-activity relationship based on thiosemicarbazone derivatives was systematically characterized and their potential activities combined with meropenem (MEM) were evaluated. Compounds and exhibited excellent activity against 10 NDM-positive isolate clinical isolates in reversing MEM resistance. Further studies demonstrated compounds and were uncompetitive NDM-1 inhibitors with i = 0.63 and 0.44 μmol/L, respectively. Molecular docking speculated that compounds and were most likely to bind in the allosteric pocket which would affect the catalytic effect of NDM-1 on the substrate meropenem. Toxicity evaluation experiment showed that no hemolysis activities even at concentrations of 1000 mg/mL against red blood cells. experimental results showed combination of MEM and compound was markedly effective in treating infections caused by NDM-1 positive strain and prolonging the survival time of sepsis mice. Our finding showed that compound might be a promising lead in developing new inhibitor to treat NDM-1 producing superbug.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.apsb.2020.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838035PMC
January 2021

Prevalence of precocious puberty among Chinese children: a school population-based study.

Endocrine 2021 Feb 2. Epub 2021 Feb 2.

Department of Clinical Epidemiology and Biostatistics, Children Health Advocacy Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: To investigate the prevalence of precocious puberty in school-based population in Zhongshan, Guangdong, China.

Methods: We recruited a total of 4058 students in grades 1-3 using a multistage stratified cluster random sampling method in a population-based cross-sectional study. We evaluated height, weight, and development of breast and pubic hair in girls, breast development was evaluated by inspection and palpation combined with ultrasound detection for overweight and obese girls, and testicular volume and development of pubic hair in boys. We estimated overall, sex-, age, and district-specific prevalence of precocious puberty and examined the association between prevalence of precocious puberty and body mass index (BMI).

Results: The unadjusted and adjusted prevalence of precocious puberty by Tanner stage was 4.74% (girls:8.78%, boys:2.58%) and 6.19% (girls:11.47%, boys:3.26%), respectively. In both urban and suburban areas, the prevalence of precocious puberty was higher in the overweight and obese group than in the normal-weight group (p < 0.05). The prevalence of precocious puberty among overweight (27.94%) and obese (48.00%) girls was higher than that of normal-weight girls (8.73%) (p value for trend < 0.05). In boys, the prevalence of precocious puberty in the obese (6.78%) group was higher than that in the normal-weight (2.86%) group (p < 0.05).

Conclusions: The prevalence of precocious puberty was high in China. Overweight and obesity was related to precocious puberty, but this correlation had gender differences and may be affected by other environmental factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-021-02630-3DOI Listing
February 2021

Genetic and Epigenetic Changes Are Rapid Responses of the Genome to the Newly Synthesized Autotetraploid .

Front Genet 2020 7;11:576260. Epub 2021 Jan 7.

State Key Laboratory of Developmental Biology of Freshwater Fish, Engineering Research Center of Polyploid Fish Reproduction and Breeding of the State Education Ministry, College of Life Sciences, Hunan Normal University, Changsha, China.

Whole genome duplication events have occurred frequently during the course of vertebrate evolution. To better understand the influence of polyploidization on the fish genome, we herein used the autotetraploid (4n = 200, RRRR) (4nRR) resulting from the whole genome duplication of (2n = 100, RR) (RCC) to explore the genomic and epigenetic alterations after polyploidization. We subsequently performed analyses of full-length transcriptome dataset, amplified fragment length polymorphism (AFLP) and methylation sensitive amplification polymorphism (MSAP) on 4nRR and RCC. By matching the results of 4nRR and RCC isoforms with reference genome in full-length transcriptome dataset, 649 and 1,971 novel genes were found in the RCC and 4nRR full-length geneset, respectively. Compared to and , 4nRR presented 3,661 unexpressed genes and 2,743 expressed genes. Furthermore, GO enrichment analysis of expressed genes in 4nRR revealed that they were enriched in meiosis I, whereas KEGG enrichment analysis displayed that they were mainly enriched in proteasome. Using AFLP analysis, we noted that 32.61% of RCC fragments had disappeared, while 32.79% of new bands were uncovered in 4nRR. Concerning DNA methylation, 4nRR exhibited a lower level of global DNA methylation than RCC. Additionally, 60.31% of methylation patterns in 4nRR were altered compared to RCC. These observations indicated that transcriptome alterations, genomic changes and regulation of DNA methylation levels and patterns had occurred in the newly established autotetraploid genomes, suggesting that genetic and epigenetic alterations were influenced by autotetraploidization. In summary, this study provides valuable novel insights into vertebrate genome evolution and generates relevant information for fish breeding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2020.576260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817996PMC
January 2021

Promotes the Progression of Colorectal Cancer Through Cdk5-Activated Wnt/β-Catenin Signaling.

Front Microbiol 2020 6;11:545251. Epub 2021 Jan 6.

Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.

Background/aims: Growing evidence supports the direct link of with colorectal cancer (CRC). However, to date, the underlying mechanism of action remains poorly understood. In this study, we examined the effects of on the progression of CRC and investigated whether cyclin-dependent kinase 5 (Cdk5) is involved in the effect through activating the Wnt/β-catenin signaling pathway.

Materials And Methods: CRC tissues and matched histologically normal specimens were collected from patients who were diagnosed with CRC and underwent surgical treatment in our hospital between January 2018 and January 2019. Two human CRC cell lines, including DLD-1 and SW480, were utilized mainly for mechanistic investigations.

Results: The abundance of was significantly greater in CRC tissues than in cancer-free specimens, which was significantly correlated with the progression of CRC. investigations revealed that significantly enhanced the proliferation and migration of CRC cells. Furthermore, significantly induced the expression of Cdk5 and activation of the Wnt/β-catenin signaling pathway. Notably, knockdown of Cdk5 significantly abrogated the effects of on cellular processes and Wnt/β-catenin signaling in relation to the progression of CRC.

Conclusion: The results of this study demonstrate that orchestrates a molecular network involving the direct role of Cdk5 in activating Wnt/β-catenin signaling to modulate CRC progression. Thus, in-depth investigations of associated molecular pathways may offer valuable insight into the pathogenesis of CRC, which may help further the development of treatment for this disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2020.545251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815597PMC
January 2021

Silicon stent placement via rigid bronchoscopy for the treatment of central airway obstruction in infants: Case series.

Medicine (Baltimore) 2021 Jan;100(2):e24244

Department of Otolaryngology, Head and Neck Surgery, the First Hospital of Jilin University, Changchun, China.

Introduction: Rigid bronchoscopy has been proven to be an excellent tool for the diagnosis and management of several causes of central airway obstruction (CAO). The invasive treatment of silicone bronchobrachial stenting has been performed in children and adults with CAO, and satisfying results were obtained in previous studies. However, there are few reports on infants with central airway obstruction treated with stenting via rigid bronchoscopy. This technique remains a challenge to pediatric thoracic surgeons, pediatric interventional pulmonologists, and otolaryngologists who struggle to treat airway obstruction disease.

Patient Concerns: Four patients were presented to our hospital with complaints of dyspnea for a period of time after their birth.

Diagnosis: Three patients were diagnosed as tracheobronchomalacia, and tracheoesophageal fistula.

Interventions: Four patients were treated with silicone stenting through rigid bronchoscopy.

Outcomes: Silicon stent was adequate for improving the obstruction of the tracheal tract. All the patients were followed-up longer than 6 months. Three patients could breathe normally; the stent migrated in only 1 patient.

Conclusion: Invasive silicone tracheobronchial stenting via rigid bronchoscopy is a viable option for infants with CAO. Choosing an appropriate size is a critical factor for success of stenting according to our experience.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000024244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808444PMC
January 2021

Sulfurization-induced partially amorphous palladium sulfide nanosheets for highly efficient electrochemical hydrogen evolution.

Chem Commun (Camb) 2021 Feb 12;57(11):1368-1371. Epub 2021 Jan 12.

School of Environmental and Chemical Engineering, Jiangsu Ocean University, Lianyungang 222005, Jiangsu, China.

A partially amorphous palladium sulfide was synthesized by sulfurizing crystalline palladium nanosheets facilely, which shows excellent activity and stability towards hydrogen evolution in alkaline media, even superior to the performance of the commercial Pt/C catalyst. The enhanced performance could be attributed to the amorphization transformation and the nanosheet morphology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cc06693aDOI Listing
February 2021

Deep-learning super-resolution light-sheet add-on microscopy (Deep-SLAM) for easy isotropic volumetric imaging of large biological specimens.

Biomed Opt Express 2020 Dec 23;11(12):7273-7285. Epub 2020 Nov 23.

School of Optical and Electronic Information- Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China.

Isotropic 3D histological imaging of large biological specimens is highly desired but remains highly challenging to current fluorescence microscopy technique. Here we present a new method, termed deep-learning super-resolution light-sheet add-on microscopy (Deep-SLAM), to enable fast, isotropic light-sheet fluorescence imaging on a conventional wide-field microscope. After integrating a minimized add-on device that transforms an inverted microscope into a 3D light-sheet microscope, we further integrate a deep neural network (DNN) procedure to quickly restore the ambiguous z-reconstructed planes that suffer from still insufficient axial resolution of light-sheet illumination, thereby achieving isotropic 3D imaging of thick biological specimens at single-cell resolution. We apply this easy and cost-effective Deep-SLAM approach to the anatomical imaging of single neurons in a meso-scale mouse brain, demonstrating its potential for readily converting commonly-used commercialized 2D microscopes to high-throughput 3D imaging, which is previously exclusive for high-end microscopy implementations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/BOE.409732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747920PMC
December 2020

Accurately Differentiating Between Patients With COVID-19, Patients With Other Viral Infections, and Healthy Individuals: Multimodal Late Fusion Learning Approach.

J Med Internet Res 2021 01 6;23(1):e25535. Epub 2021 Jan 6.

Department of Public Health Sciences, College of Health and Human Services, University of North Carolina Charlotte, Charlotte, NC, United States.

Background: Effectively identifying patients with COVID-19 using nonpolymerase chain reaction biomedical data is critical for achieving optimal clinical outcomes. Currently, there is a lack of comprehensive understanding in various biomedical features and appropriate analytical approaches for enabling the early detection and effective diagnosis of patients with COVID-19.

Objective: We aimed to combine low-dimensional clinical and lab testing data, as well as high-dimensional computed tomography (CT) imaging data, to accurately differentiate between healthy individuals, patients with COVID-19, and patients with non-COVID viral pneumonia, especially at the early stage of infection.

Methods: In this study, we recruited 214 patients with nonsevere COVID-19, 148 patients with severe COVID-19, 198 noninfected healthy participants, and 129 patients with non-COVID viral pneumonia. The participants' clinical information (ie, 23 features), lab testing results (ie, 10 features), and CT scans upon admission were acquired and used as 3 input feature modalities. To enable the late fusion of multimodal features, we constructed a deep learning model to extract a 10-feature high-level representation of CT scans. We then developed 3 machine learning models (ie, k-nearest neighbor, random forest, and support vector machine models) based on the combined 43 features from all 3 modalities to differentiate between the following 4 classes: nonsevere, severe, healthy, and viral pneumonia.

Results: Multimodal features provided substantial performance gain from the use of any single feature modality. All 3 machine learning models had high overall prediction accuracy (95.4%-97.7%) and high class-specific prediction accuracy (90.6%-99.9%).

Conclusions: Compared to the existing binary classification benchmarks that are often focused on single-feature modality, this study's hybrid deep learning-machine learning framework provided a novel and effective breakthrough for clinical applications. Our findings, which come from a relatively large sample size, and analytical workflow will supplement and assist with clinical decision support for current COVID-19 diagnostic methods and other clinical applications with high-dimensional multimodal biomedical features.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/25535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790733PMC
January 2021

Minutes-timescale 3D isotropic imaging of entire organs at subcellular resolution by content-aware compressed-sensing light-sheet microscopy.

Nat Commun 2021 01 4;12(1):107. Epub 2021 Jan 4.

School of Optical and Electronic Information- Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, 430074, Wuhan, China.

Rapid 3D imaging of entire organs and organisms at cellular resolution is a recurring challenge in life science. Here we report on a computational light-sheet microscopy able to achieve minute-timescale high-resolution mapping of entire macro-scale organs. Through combining a dual-side confocally-scanned Bessel light-sheet illumination which provides thinner-and-wider optical sectioning of deep tissues, with a content-aware compressed sensing (CACS) computation pipeline which further improves the contrast and resolution based on a single acquisition, our approach yields 3D images with high, isotropic spatial resolution and rapid acquisition over two-order-of-magnitude faster than conventional 3D microscopy implementations. We demonstrate the imaging of whole brain (~400 mm), entire gastrocnemius and tibialis muscles (~200 mm) of mouse at ultra-high throughput of 5~10 min per sample and post-improved subcellular resolution of ~ 1.5 μm (0.5-μm iso-voxel size). Various system-level cellular analyses, such as mapping cell populations at different brain sub-regions, tracing long-distance projection neurons over the entire brain, and calculating neuromuscular junction occupancy across whole muscle, are also readily accomplished by our method.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-20329-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782498PMC
January 2021

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

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

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

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

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

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

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

Conclusions: This study found novel mutations in the CIITA gene of BLS II, which complemented the mutation spectrum and contributed to the diagnosis, treatment, genetic counseling and prenatal diagnosis of BLS II.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12932/AP-020720-0898DOI Listing
January 2021

Mechanical force-driven TNFα endocytosis governs stem cell homeostasis.

Bone Res 2021 Jan 1;8(1):44. Epub 2021 Jan 1.

Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Mesenchymal stem cells (MSCs) closely interact with the immune system, and they are known to secrete inflammatory cytokines in response to stress stimuli. The biological function of MSC-derived inflammatory cytokines remains elusive. Here, we reveal that even under physiological conditions, MSCs produce and release a low level of tumor necrosis factor alpha (TNFα), which is unexpectedly required for preserving the self-renewal and differentiation of MSCs via autocrine/paracrine signaling. Furthermore, TNFα critically maintains MSC function in vivo during bone homeostasis. Mechanistically, we unexpectedly discovered that physiological levels of TNFα safeguard MSC homeostasis in a receptor-independent manner through mechanical force-driven endocytosis and that endocytosed TNFα binds to mammalian target of rapamycin (mTOR) complex 2 and restricts mTOR signaling. Importantly, inhibition of mTOR signaling by rapamycin serves as an effective osteoanabolic therapeutic strategy to protect against TNFα deficiency and mechanical unloading. Collectively, these findings unravel the physiological framework of the dynamic TNFα shuttle-based mTOR equilibrium that governs MSC and bone homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41413-020-00117-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775432PMC
January 2021

Towards a neural model of creative evaluation in advertising: an electrophysiological study.

Sci Rep 2020 12 15;10(1):21958. Epub 2020 Dec 15.

Shanghai Mental Health Center, Shanghai Jiaotong University, 600 Wanping South Road, Xuhui District, Shanghai, 200030, China.

Although it is increasingly recognized that evaluation is a key phase for a two-fold creativity model, the neural model is not yet well understood. To this end, we constructed a theoretical model of creative evaluation and supported it with neural evidence through event-related potentials (ERPs) technology during a creative advertising task. Participants were required to evaluate the relationship between target words and advertising that systematically varied in novelty and usefulness. The ERPs results showed that (a) the novelty-usefulness and novelty-only conditions evoked a larger N1-P2 amplitude, reflecting an automatic attentional bias to novelty, and (b) these two novelty conditions elicited a larger N200-500 amplitude, reflecting an effort to process the novel content; (c) the novelty-usefulness and usefulness-only conditions induced a larger LPC amplitude, reflecting that valuable associations were formed through retrieval of relevant memories. These results propose a neural model of creative evaluation in advertising: the N1-P2, N200-500, and LPC should be the key indices to define three sub-processes of novelty perception, conception expansion, and value selection, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-79044-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738497PMC
December 2020

Psychomotor development and attention problems caused by a splicing variant of CNKSR2.

BMC Med Genomics 2020 12 9;13(1):182. Epub 2020 Dec 9.

Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People's Republic of China.

Background: Mutations in CNKSR2 have been described in patients with neurodevelopmental disorders characterized by childhood epilepsy, language deficits, and attention problems. The encoded protein plays an important role in synaptic function.

Case Presentation: Whole-exome sequencing was applied to detect pathogenic variants in a patient with clinical symptoms of psychomotor development, attention deficit, poor logical thinking ability, and an introverted personality, but without epilepsy or any significant electroencephalogram changes. Genetic study revealed a splicing mutation (c.1904 + 1G > A) and RT-PCR revealed aberrant splicing of exon 16, leading to a reading-frame shift and a truncated protein in the PH domain.

Conclusions: This is the first report of a splicing variant of CNKSR2, and the unique clinical features of this pedigree will help extend our understanding of the genetic and phenotypic spectra of CNKSR2-related disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12920-020-00844-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727132PMC
December 2020

CRL4 dependent opposing stability control over the chromatin remodeler LSH orchestrates epigenetic dynamics in ferroptosis.

Cell Death Differ 2020 Dec 7. Epub 2020 Dec 7.

Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 100191, Beijing, China.

Despite the emerging evidence on ferroptosis implicated in diverse pathologies, molecular linkage between oxidative inducers and chromatin as epigenetic memory carrier for its propagation remains elusive. Here, we report the identification of two WD40 proteins DCAF8 and WDR76 as substrate adapter and molecular inhibitor respectively of the Cullin-4 RING ubiquitin ligase (CRL4) system for stability control of chromatin remodeler LSH. Degradation analysis and CRL4-DCAF8 complex reconstitution demonstrate that CRL4 is a bona fide E3 ligase for LSH. In contrast, WDR76 antagonizes DCAF8-targeted LSH proteolysis through competitive inhibition of the holo-CRL4-LSH complex assembly. Importantly, this opposing regulatory strategy is utilized in lipid hydroperoxide induced ferroptosis, where we identify key redox homeostasis genes significantly regulated by the DCAF8/WDR76/LSH axis through transcriptomic epistasis analysis. This regulation is mechanistically attributed to DNA hydroxymethylation fostered WDR76 interaction with LSH and increased ratio of DCAF8 to WDR76 for antagonistic LSH association accompanying decreased DNA oxidation along with ROS overproduction. Evaluation of epigenetic dynamics at ferroptosis gene promoters reveals linker histone H1- and LSH-associated transcriptional repression is coordinately removed upon lipid peroxidation stress. Together with the phenotypes driven by WDR76 and DCAF8 manipulations, these data identify DCAF8- and WDR76-adapted oxidative damage sensing through DNA hydroxymethylation for LSH degradation control as a crucial nexus in epigenetic regulation of ferroptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41418-020-00689-5DOI Listing
December 2020

[Identification of Candidate Biomarkers for EGFR-T790M Drug-resistant 
Gene Mutation in Advanced Lung Adenocarcinoma].

Zhongguo Fei Ai Za Zhi 2020 Nov;23(11):941-947

Department of Pulmonary Medicine Ward 1, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi 830000, China.

Background: Osimertinib is approved by Food and Drug Administration for patients with advanced non-small cell lung cancer carrying EGFR-T790M mutations. Osimertinib therapy was missed in many patients who were unable to perform biopsy due to occult lesion progression or weak body. In this study. We hope that some proteins associated with predicting EGFR-T790M resistance could be screened from the serum to provide help for clinical medication. The aim of this study is to explore the protein associated with EGFR-T790M drug resistance gene and provide help for clinical medication.

Methods: In this study, 36 patients with advanced lung adenocarcinoma treated by gefitinib were included. After the disease progression of the patients, biopsy was performed. 18 patients in the EGFR-T790M mutation group and 18 patients in the non-EGFR-T790M mutation group were detected by the ARMS method. Serum of patients with drug resistance was collected, and proteins related to EGFR-T790M resistance were screened by isotopic marker relative and absolute quantitative marker combined with two-dimensional liquid chromatography tandem mass spectrometry proteomics technology.

Results: Seventeen different proteins were screened out, including 6 up-regulated proteins and 11 down-regulated proteins associated with EGFR-T790M gene mutation, which were mainly involved in 31 biological processes, 7 cell components and 26 molecular functions. Twelve enrichment pathways were identified, among which the highest enrichment index was the coagulation cascade pathway.

Conclusions: Seventeen proteins associated with EGFR-T790M resistance were found, and proteins involved in the coagulation cascade pathway are expected to be biomarkers associated with predicting EGFR-T790M resistance mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3779/j.issn.1009-3419.2020.104.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679218PMC
November 2020

Deep learning-enabled efficient image restoration for 3D microscopy of turbid biological specimens.

Opt Express 2020 Sep;28(20):30234-30247

Though three-dimensional (3D) fluorescence microscopy has been an essential tool for modern life science research, the light scattering by biological specimens fundamentally prevents its more widespread applications in live imaging. We hereby report a deep-learning approach, termed ScatNet, that enables reversion of 3D fluorescence microscopy from high-resolution targets to low-quality, light-scattered measurements, thereby allowing restoration for a blurred and light-scattered 3D image of deep tissue. Our approach can computationally extend the imaging depth for current 3D fluorescence microscopes, without the addition of complicated optics. Combining ScatNet approach with cutting-edge light-sheet fluorescence microscopy (LSFM), we demonstrate the image restoration of cell nuclei in the deep layer of live Drosophilamelanogaster embryos at single-cell resolution. Applying our approach to two-photon excitation microscopy, we could improve the signal-to-noise ratio (SNR) and resolution of neurons in mouse brain beyond the photon ballistic region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.399542DOI Listing
September 2020

TRPS1 mutation detection in Chinese patients with Tricho-rhino-phalangeal syndrome and identification of four novel mutations.

Mol Genet Genomic Med 2020 10 10;8(10):e1417. Epub 2020 Aug 10.

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

Background: Tricho-rhino-phalangeal syndrome (TRPS) is a rare autosomal dominant disorder characterized by craniofacial and skeletal malformations including short stature, thin scalp hair, sparse lateral eyebrows, a pear-shaped nose, and cone-shaped epiphyses. This condition is caused by haploinsufficiency or dominant-negative effect of the TRPS1 gene.

Methods: In this study, we analyzed the clinical and genetic data of five unrelated TRPS patients. They were suspected of having TRPS on the basis of clinical and radiological features including typical hair and facial features, as well as varying degrees of skeletal abnormalities. Next-generation sequencing was performed to identify variants of the TRPS1 gene in the five patients.

Results: In patient 1, we found a novel mutation at c.1338C>A (p.Tyr446*) (de novo). Patient 2 had a novel phenotype of hydrocephaly and Arnold-Chiari syndrome and we also found a maternally inherited novel mutation at c.2657C>A (p.Ser886*). Patient 3 had a de novo novel mutation at c.2726G>C (p.Cys909Ser) leading to more severe phenotypes. Patient 4 had a paternally inherited known mutation at c.2762G>A (p.Arg921Gln). Patient 5 with a novel phenotype of hepatopathy had a novel deletion at [GRCh37] del(8)(q23.3-q24.11) chr8:g.116,420,724-119,124,058 (over 2,700 kb). In addition, the patient 3 who harboring missense variants in the GATA binding domain of TRPS1 showed more severe craniofacial and skeletal phenotypes.

Conclusions: We describe four novel mutations and two novel phenotypes in five patients. The mutational and phenotypic spectrum of TRPS is broadened by our study on TRPS mutations. Our results reveal the significance of molecular analysis of TRPS1 for improving the clinical diagnosis of TRPS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mgg3.1417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549555PMC
October 2020

Proteomic Analysis of Protein Ubiquitination Events in Human Primary and Metastatic Colon Adenocarcinoma Tissues.

Front Oncol 2020 10;10:1684. Epub 2020 Sep 10.

Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Protein ubiquitination is essential for multiple physiological processes through regulating the stability or function of target proteins and has been found to play critical roles in human cancers. However, the protein ubiquitination profile of human metastatic colon adenocarcinoma tissue has not been elucidated yet. In this study, a proprietary ubiquitin branch (K-ε-GG) antibody-based label-free quantitative proteomics and bioinformatics were performed to identify the global protein ubiquitination profile between human primary (Colon) and metastatic colon adenocarcinoma (Meta) tissues. A total of 375 ubiquitination sites from 341 proteins were identified as differentially modificated (| Fold change| > 1.5, < 0.05) in Meta group compared with the Colon group. Among them, 132 ubiquitination sites from 127 proteins were upregulated and 243 ubiquitination sites from 214 proteins were downregulated in Meta group. Fifteen ubiquitination motifs were found. Furthermore, GO and KEGG pathway analysis indicated that proteins with altered ubiquitination in Meta group were enriched in pathways highly related to cancer metastasis, such as RNA transport and cell cycle. We speculate that the altered ubiquitination of CDK1 may be a pro-metastatic factor in colon adenocarcinoma. This study provides novel scientific evidences to elucidate the biological functions of protein ubiquitination in human colon adenocarcinoma and insights into its potential mechanisms of colon cancer metastasis, which would be helpful to discover novel biomarkers and therapeutic targets for effective treatment of colon cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.01684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511592PMC
September 2020