Morphological transformations of vesicles with confined flexible filaments.

A fundamental understanding of cell shaping with confined flexible filaments, including microtubules, actin filaments, and engineered nanotubes, has been limited by the complex interplay between the cell membrane and encapsulated filaments. Here, combining theoretical modeling and molecular dynamics simulations, we investigate the packing of an open or closed filament inside a vesicle. Depending on the relative stiffness and size of the filament to the vesicle as well as the osmotic pressure, the vesicle could evolve from an axisymmetric configuration to a general configuration with a maximum of three reflection planes, and the filament could bend in or out of plane or even coil up. A plethora of system morphologies are determined. Morphological phase diagrams predicting conditions of shape and symmetry transitions are established. Organization of actin filaments or bundles, microtubules, and nanotube rings inside vesicles, liposomes, or cells are discussed. Our results provide a theoretical basis to understand cell shaping and cellular stability and to help guide the development and design of artificial cells and biohybrid microrobots.

Multiple myeloma with high expression of SLC7A11 is sensitive to erastin-induced ferroptosis.

Ferroptosis, a nonapoptotic form of cell death marked by iron-dependent peroxidation of phospholipids, is associated with the occurrence and progression of tumors. Erastin, a selective inhibitor of the cystine/glutamate transporter system Xc-, can induce the ferroptosis of cancer cells. Multiple myeloma (MM) has been reported to be insensitive to erastin-induced ferroptosis. However, we found the erastin sensitivity of different MM cells varied widely. Specifically, SLC7A11 abundance determined the sensitivity of MM cells to erastin-induced ferroptosis. MM cells expressing a high SLC7A11 level were more sensitive to erastin-induced ferroptosis than cells expressing a low level of SLC7A11. Moreover, the expression of SLC7A11 gradually increased with the progression of plasma cell dyscrasias. Survival analysis indicated that high levels of SLC7A11 predicted a poor prognosis for MM patients. Knocking down SLC7A11 expression significantly inhibited the proliferation of MM cells and induced ferroptotic cell death. Additionally, we revealed that the long noncoding RNA (lncRNA) SLC7A11-AS1 was a critical regulatory factor of SLC7A11 expression. SLC7A11-AS1 overexpression diminished SLC7A11 levels, leading to the ferroptosis of MM cells. In summary, our data show that heterogeneous SLC7A11 expression affects MM cell sensitivity to ferroptosis, providing a theoretical basis for improving the clinical treatment of MM.

A promising natural product in diffuse large B-cell lymphoma therapy by targeting PIM1.

Diffuse large B-cell lymphoma (DLBCL) is the most common and aggressive type of B-cell lymphoma. Unfortunately, about one-third of patients either relapse after the initial treatment or are refractory to first-line therapy, indicating a need for new treatment modalities. PIM serine/threonine kinases are proteins that are associated with genetic mutations, overexpression, or translocation events in B-cell lymphomas. We conducted an integrative analysis of whole-exome sequencing in 52 DLBCL patients, and no amplification, mutation, or translocation of the PIM1 gene was detected. Instead, analyses of TCGA and GTEx databases identified that PIM1 expression was increased in DLBCL samples compared to normal tissue, and high expression levels were associated with poor overall survival. Moreover, interference of PIM1 significantly suppressed DLBCL cell proliferation. In addition, we identified anwulignan, a natural small-molecule compound, as a PIM1 inhibitor. Anwulignan directly binds to PIM1 and exerts antitumor effects on DLBCL in vitro and in vivo by inducing apoptosis, cell cycle arrest, and autophagic cell death. Furthermore, we identified an effective synergistic combination between anwulignan and chidamide. Our findings suggested that PIM1 could be a therapeutic target and prognostic factor for DLBCL, and anwulignan holds promise for future development as a natural product for treatment.

Identification of a distal enhancer that determines the expression pattern of acute phase marker C-reactive protein.

C-reactive protein (CRP) is a major acute phase protein and inflammatory marker, the expression of which is largely liver specific and highly inducible. Enhancers are regulatory elements critical for the precise activation of gene expression, yet the contributions of enhancers to the expression pattern of CRP have not been well defined. Here, we identify a constitutively active enhancer (E1) located 37.7 kb upstream of the promoter of human CRP in hepatocytes. By using chromatin immunoprecipitation, luciferase reporter assay, in situ genetic manipulation, CRISPRi, and CRISPRa, we show that E1 is enriched in binding sites for transcription factors STAT3 and C/EBP-ß and is essential for the full induction of human CRP during the acute phase. Moreover, we demonstrate that E1 orchestrates with the promoter of CRP to determine its varied expression across tissues and species through surveying activities of E1-promoter hybrids and the associated epigenetic modifications. These results thus suggest an intriguing mode of molecular evolution wherein expression-changing mutations in distal regulatory elements initiate subsequent functional selection involving coupling among distal/proximal regulatory mutations and activity-changing coding mutations.

Dysregulation of alternative splicing contributes to multiple myeloma pathogenesis.

BACKGROUND: Dysregulation of alternative splicing (AS) triggers many tumours, understanding the roles of splicing events during tumorigenesis would open new avenues for therapies and prognosis in multiple myeloma (MM). METHODS: Molecular, genetic, bioinformatic and statistic approaches are used to determine the mechanism of the candidate splicing factor (SF) in myeloma cell lines, myeloma xenograft models and MM patient samples. RESULTS: GSEA reveals a significant difference in the expression pattern of the alternative splicing pathway genes, notably enriched in MM patients. Upregulation of the splicing factor SRSF1 is observed in the progression of plasma cell dyscrasias and predicts MM patients' poor prognosis. The c-indices of the Cox model indicated that SRSF1 improved the prognostic stratification of MM patients. Moreover, SRSF1 knockdown exerts a broad anti-myeloma activity in vitro and in vivo. The upregulation of SRSF1 is caused by the transcription factor YY1, which also functions as an oncogene in myeloma cells. Through RNA-Seq, we systematically verify that SRSF1 promotes the tumorigenesis of myeloma cells by switching AS events. CONCLUSION: Our results emphasise the importance of AS for promoting tumorigenesis of MM. The candidate SF might be considered as a valuable therapeutic target and a potential prognostic biomarker for MM.

Endocarditis due to Aggregatibacter Segnis: a rare case report.

BACKGROUND: As a member of the HACEK group, Aggregatibacter segnis (A. segnis) is a fastidious Gram-negative coccobacillus that resides in the human oropharyngeal flora. Infective endocarditis caused by A. segnis is rarely reported. CASE PRESENTATION: A 31-year-old male was admitted to our hospital for a 3-month history of intermittent high fever, chills, and chest distress. On presentation, he was febrile and tachycardic but otherwise with stable vital signs. Physical examination revealed systolic murmurs in the aortic and mitral valve areas. Pitting edema was evident in the lower extremities. Transthoracic echocardiography demonstrated multiple vegetations in the mitral and aortic valves. Severe regurgitation of the aortic valve and left heart dysfunction were also detected. With the suspicion of infective endocarditis and heart failure, we immediately performed microbiological tests and arranged the cardiac replacement surgery. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and metagenomic next-generation sequencing (mNGS) identified A. segnis from the bloodstream. While the surgical specimen culture was negative, the mNGS was positive for A. segnis. The patient was treated with ceftriaxone for four weeks and discharged. He remained clinically well, with laboratory results restored. CONCLUSION: This is the first report of A. segnis infective endocarditis that combined MALDI-TOF and metagenomic next-generation sequencing in the diagnosis. The hypothesis-independent molecular techniques can outperform conventional tools to prevent diagnostic delay.

Seven Immune-Related Genes' Prognostic Value and Correlation with Treatment Outcome in Head and Neck Squamous Cell Carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is a growing concern worldwide, due to its poor prognosis, low responsiveness to treatment, and drug resistance. Since immunotherapy effectively improves HNSCC patients' survival status, it is important to continuously explore new immune-related predictive factors to accurately predict the immune landscape and clinical outcomes of individuals suffering from HNSCC. Methods: The HNSCC transcriptome profiling of RNA-sequencing data was retrieved from TCGA database, and the microarray of GSE27020 was obtained from the GEO database for validation. The differentially expressed genes (DEGs) between HNSCC and normal samples were identified by multiple test corrections in TCGA database. The univariate and multivariate Cox analyses were performed to identify proper immune-related genes (IRGs) to construct a risk model. The Cox regression coefficient was employed for calculation of the risk score (RS) of IRG signature. The median value of RS was utilized as a basis to classify individuals with HNSCC into high- and low-risk groups. The Kaplan-Meier (K-M) survival analysis and receiver operating characteristic (ROC) curves were employed for the identification of the prognostic significance and precision of the IRG signature. The signature was also evaluated based on clinical variables, predictive nomogram, mutation analysis, infiltrating immune cells, immune-related pathways, and chemotherapeutic efficacy. The protein-protein interaction (PPI) network and functional enrichment pathway investigations were utilized to explore possible potential molecular mechanisms. Finally, the hub gene's differential mRNA expression levels were evaluated by means of the Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA) was utilized for the validation of their translational levels. Results: Collectively, 1593 DEGs between HNSCC and normal samples were identified, of which 136 IRGs were differentially expressed. Then, the 136 immune-related DEGs were mostly enriched in the cytokine-related signaling pathways by GO and KEGG analyses. After that, a valuable signature based on seven genes (DKK1, GAST, IGHM, IL12RB2, SLURP1, STC2, and TNFRSF4) was designed. The HNSCC patients into the low-risk group and the high-risk group were divided by using the median RS; the HNSCC patients in the high-risk group had a worse survival than those in the low-risk group. The risk signature was verified to be an independent predictive marker for HNSCC patients. Meanwhile, the RS had the largest contribution to survival of these patients based on the predictive nomogram. In addition, the low-risk HNSCC patients exhibited significantly enriched immune cells, along with an association with high chemosensitivity. Conclusion: The constructed gene signature can independently function as a predictive indicator for the clinical features of HNSCC patients. The low-risk HNSCC subjects might benefit from immunotherapy and chemotherapy.

Identification of three novel B cell epitopes in ORF2 protein of the emerging goose astrovirus and their application.

The outbreak of goose gout disease caused by novel goose astrovirus type 1 (GAstV-1) has resulted in huge economic losses to the goose industry in China since 2017. However, little is known about the B cell epitopes in major antigen of GAstV-1 and the serological approach for detection of GAstV-1 is not available. In this study, three novel monoclonal antibodies (mAbs) against the ORF2 protein were first generated and designated as 3G6, 5H7, and 6C6, respectively. Epitope mapping revealed that mAb 3G6, 5H7, and 6C6 recognized 695AVRFEKGGHE704, 685EKALSAPQAG694, and 635DDDPLSDVTS644 in ORF2, respectively. Sequence alignments found that the three epitopes were highly conserved in GAstV-1 but not in other AAstV members. Moreover, a mAb-based sandwich ELISA for the detection of GAstV-1 was first developed using mAb 6C6. The sandwich ELISA only reacted with GAstV-1 but not with GAstV-2 and the other goose-associated viruses tested. The limit of the detection of the sandwich ELISA reaches 1.58 × 103 TCID50/mL of GAstV-1. Notably, mAb 6C6 could also efficiently react with the GAstV-1 in tissue frozen sections of the clinical infected goose through IFA. The mAbs generated in this study pave the way for further studying on the role of ORF2 in the infection and pathogenesis of GAstV, and the sandwich ELISA and the tissue frozen section-IFA approaches established here provide efficient and rapid serological diagnostic tools for detection of GAstV-1. KEY POINTS: • Three novel B cell epitopes were identified in ORF2 of GAstV-1. • mAb-based ELISA and IFA for detection of GAstV-1 were developed.

Anwulignan Ameliorates the Intestinal Ischemia/Reperfusion.

Anwulignan is one of the monomer compounds in the lignans from Schisandra sphenanthera In this study, we observed the effect of anwulignan on intestinal ischemia/reperfusion (II/R) injury in male Sprague-Dawley rats and explored the underlying mechanisms. The results showed that pretreatment with oral anwulignan could significantly increase the mesenteric blood microcirculatory flow velocity; relieve the congestion and pathologic injury of jejunum; enhance the autonomic tension of jejunum smooth muscle and its reactivity to acetylcholine; increase the activities of superoxide dismutase, catalase, glutathione S-transferase, and choline acetyltransferase; increase the contents of acetylcholine and glutathione in the serum or jejunal tissue; decrease the activities of myeloperoxidase, protein kinase C, and nicotinamide adenine dinucleotide phosphate oxidase; reduce the contents of malondialdehyde, 8-hydroxy-2-deoxyguanosine, nicotinamide adenine, reactive oxygen species, tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß; increase the expression levels of muscarinic receptor 3, PI3K, phosphorylation protein kinase B, p-GSK3ß Ser9, Nrf2, p-Nrf2, heme oxygenase (decycling) 1, and b-cell lymphoma 2 in the jejunal tissue; and decrease the expression levels of p-GSK3ß Tyr216, kelch-like ECH-associated protein 1, Bax, and cleaved caspase-3, suggesting that anwulignan can ameliorate II/R-induced jejunal tissue injury in rats and that the mechanism may be related to its activating the PI3K/protein kinase B pathway and then regulating the Nrf2/Anti-oxidative Response Element signaling pathway and the expression of apoptosis-related proteins to play antioxidant and antiapoptotic roles. SIGNIFICANCE STATEMENT: Anwulignan can significantly reduce jejunal tissue injury and the production of inflammatory factors in rats with intestinal ischemia-reperfusion injury, improve the antioxidant capacity, and reduce the apoptosis of jejunal tissue, and it has the effect of significantly improving intestinal ischemia-reperfusion injury in rats, suggesting that anwulignan may be used as a potential drug for the prevention and treatment of intestinal ischemia-reperfusion injury or a resource for the development of health food.

Recognition of conserved antigens by Th17 cells provides broad protection against pulmonary Haemophilus influenzae infection.

Nontypeable Haemophilus influenzae (NTHi) is a major cause of community acquired pneumonia and exacerbation of chronic obstructive pulmonary disease. A current effort in NTHi vaccine development has focused on generating humoral responses and has been greatly impeded by antigenic variation among the numerous circulating NTHi strains. In this study, we showed that pulmonary immunization of mice with killed NTHi generated broad protection against lung infection by different strains. While passive transfer of immune antibodies protected only against the homologous strain, transfer of immune T cells conferred protection against both homologous and heterologous strains. Further characterization revealed a strong Th17 response that was cross-reactive with different NTHi strains. Responding Th17 cells recognized both cytosolic and membrane-associated antigens, while immune antibodies preferentially responded to surface antigens and were highly strain specific. We further identified several conserved proteins recognized by lung Th17 cells during NTHi infection. Two proteins yielding the strongest responses were tested as vaccine candidates by immunization of mice with purified proteins plus an adjuvant. Immunization induced antigen-specific Th17 cells that recognized different strains and, upon adoptive transfer, conferred protection. Furthermore, immunized mice were protected against challenge with not only NTHi strains but also a fully virulent, encapsulated strain. Together, these results show that the immune mechanism of cross-protection against pneumonia involves Th17 cells, which respond to a broad spectrum of antigens, including those that are highly conserved among NTHi strains. These mechanistic insights suggest that inclusion of Th17 antigens in subunit vaccines offers the advantage of inducing broad protection and complements the current antibody-based approaches.

Identification of novel biomarkers affecting the metastasis of colorectal cancer through bioinformatics analysis and validation through qRT-PCR.

BACKGROUND: Tumor progression and distant metastasis are the main causes of deaths in colorectal cancer (CRC) patients, and the molecular mechanisms in CRC metastasis have not been completely discovered. METHODS: We identified differentially expressed genes (DEGs) and lncRNAs (DELs) of CRC from The Cancer Genome Atlas (TCGA) database. Then we conducted the weighted gene co-expression network analysis (WGCNA) to investigate co-expression modules related with CRC metastasis. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, DEG-DEL co-expression network and survival analyses of significant modules were also conducted. Finally, the expressions of selected biomarkers were validated in cell lines by quantitative real-time PCR (qRT-PCR). RESULTS: 2032 DEGs and 487 DELs were involved the construction of WGCNA network, and greenyellow, turquoise and brown module were identified to have more significant correlation with CRC metastasis. GO and KEGG pathway analysis of these three modules have proven that the functions of DEGs were closely involved in many important processes in cancer pathogenesis. Through the DEG-DEL co-expression network, 12 DEGs and 2 DELs were considered as hub nodes. Besides, survival analysis showed that 30 DEGs were associated with the overall survival of CRC. Then 10 candidate biomarkers were chosen for validation and the expression of CA2, CHP2, SULT1B1, MOGAT2 and C1orf115 were significantly decreased in CRC cell lines when compared to normal human colonic epithelial cells, which were consistent with the results of differential expression analysis. Especially, low expression of SULT1B1, MOGAT2 and C1orf115 were closely correlated with poorer survival of CRC. CONCLUSION: This study identified 5 genes as new biomarkers affecting the metastasis of CRC. Besides, SULT1B1, MOGAT2 and C1orf115 might be implicated in the prognosis of CRC patients.

Sidewall contact regulating the nanorod packing inside vesicles with relative volumes.

Intracellular packing of one-dimensional and rodlike materials plays an important role in many biological processes such as cell mimicking, microtubule protrusion, cell division, frustrated phagocytosis, and pathogenicity. To understand the mechanical interplay between cells/intracellular membranous organelles and encapsulated rodlike materials, we perform theoretical analyses to investigate how the morphologies and mechanical behaviors of lipid vesicles of given relative volumes are regulated by encapsulated rigid nanorods of finite diameters and selected geometries, including a cylindrical nanorod, a nanorod with one widened end, and a cone-shaped nanorod. The contact between the vesicle protrusion and the sidewall of the rod, neglected in most theoretical studies, is shown to play an important role in regulating vesicle tubulation, membrane tension, and axial contact force on the nanorod. As the nanorod length increases, the confining vesicle evolves from a prolate into different shapes, such as a lemon, a conga drum, a cherry, and a bowling pin, depending on the radical size of the nanorod and the relative vesicle volume. The corresponding morphological phase diagrams are determined. Moreover, phase diagrams of the buckling of the encapsulated nanorods are determined based on the classical Euler buckling theory. It is shown that there exists an optimal filament number at which the encapsulated weakly cross-linked filament bundle maintains the largest length in a mechanically stable state. Similarities and differences between the nanorod packing in vesicles at a given pressure difference and a relative volume are discussed. Our results provide valuable insight into the biophysics underlying cell interactions with one-dimensional and rodlike materials.

PROGRAMMED CELL DEATH-LIGAND 1 OVEREXPRESSION IN THYROID CANCER.

OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) expression on tumor tissue has been associated with favorable response to anti-programmed cell death-receptor 1/PD-L1 therapy in many human cancers. Studies have reported that PD-L1 is also expressed in thyroid cancer. The objective of this paper is to introduce the potential predictive and therapeutic values of PD-L1 in thyroid cancer. METHODS: A literature search was conducted in the PubMed database using the terms "PD-L1," "B7-H1," and "thyroid cancer." PD-L1 positivity was determined by immunohistochemical assay. RESULTS: The frequency of PD-L1 positivity in different studies ranged from 6.1 to 82.5% in papillary thyroid cancer (PTC) patients and 22.2 to 81.2% in anaplastic thyroid cancer (ATC) patients. PD-L1 positivity rate was higher in ATC than in PTC within the same studies, and its expression intensity was significantly higher in tumor tissue than in the corresponding nontumor thyroid tissues. Moreover, PD-L1 expression was positively associated with the aggressiveness and recurrence of thyroid cancers and negatively associated with the differentiation status and outcomes. PD-L1 checkpoint pathway blockade may emerge as a promising therapeutic target in the treatment of thyroid cancers. CONCLUSION: PD-L1 is a potential biomarker to predict the recurrence and prognosis of thyroid cancers. It is also a novel immunotherapy target for optimizing the management landscape of radioiodine-refractory and ATCs. ABBREVIATIONS: ATC = anaplastic thyroid cancer; DTC = differentiated thyroid cancer; IHC = immunohistochemical; OS = overall survival; PD-1 = programmed cell death-receptor 1; PD-L1 = programmed cell death-ligand 1; PD-L2 = programmed cell death-ligand 2; PTC = papillary thyroid cancer; TNM = tumor-node-metastasis; Treg = regulatory T cell.

A Preliminary Study of Ankle Single Photon Emission Computed Tomography/Computed Tomography in Patients With Bony Impingement Syndrome: Association With the Visual Analogue Scale Pain Score.

Both osteoarthritis and impingement syndrome are the disorders commonly observed in sports medicine. However, failure in pain alleviation by surgical intervention introduces challenges in the diagnosis and decision-making for orthopedists. Hybrid single photon emission computed tomography/computed tomography (SPECT/CT) provides both functional and structural information of ankle pathology. The purpose of this retrospective study was to evaluate whether bone tracer uptake by ankle SPECT/CT is related to the lesion type and visual analog scale (VAS) pain score for patients with osteoarthritis and bony impingement. Fifty individuals with chronic ankle pain who underwent pretreatment ankle SPECT/CT were included in the current study. The median follow-up period was 2.5 (range 1.8 to 3.2) years. The lesion types were categorized by the positions of anatomical changes and bone tracer uptake. The VAS pain score was recorded 2 weeks before and 1.5 year after surgical intervention. Twenty-nine (58%) of 50 patients had osseous impingement. Among them, 16 (55.2%), 4 (13.8%), and 9 (31%) patients had anterior, posterior, and both types of ankle impingement, respectively. The uptake grade of bone tracer was significantly related to the lesion type of ankle impingement (p < .001). The VAS pain score was significantly correlated with bone tracer uptake before treatment (p < .001). Bone tracer uptake was related to the lesion type of impingement detected by SPECT/CT and was confirmed by surgical findings. The VAS pain score was significantly correlated with the bone tracer uptake. Preoperative ankle SPECT/CT may be helpful to clinically correlate the VAS pain score in the pre- and postsurgical periods for patients with osteoarthritis and bony impingement syndrome.

Circulating Tumor Cells Correlate with Clinicopathological Features and Outcomes in Differentiated Thyroid Cancer.

BACKGROUND/AIMS: As biomarkers, circulating tumor cells (CTCs) from solid tumors can predict metastases and prognoses, and help monitor treatment efficacy. However, conventional CellSearch methods have low sensitivity to differentiated thyroid cancer (DTC) CTCs. In this study, for the first time, we used negative enriching (NE) immunofluorescence-in situ hybridization (iFISH) of chromosome 8 to capture and identify CTCs in DTC patients; and investigated how CTCs correlate with clinicopathological factors and prognosis in DTC patients with distant metastases (DM). METHODS: In this prospective study, we enrolled 72 patients with DTC before they underwent 131I treatment, and 30 healthy controls (HC). Their CTCs were measured in 7.5 ml peripheral blood using the NE-iFISH technique. CTC was defined by the aneuploidy. RESULTS: We detected CTCs in 62 (86.1%) of the 72 subjects with DTC. The mean number of CTCs in patients with DTC with DM (DM+) was significantly higher than in the HC group (P< 0.001) and DTC patients without DM (DM-; P=0.0016). We found CTCs ≥ 5 was significantly associated with DM+ DTC (P=0.009; sensitivity: 64.3%; specificity: 83.8%); CTCs ≥ 7 was related to poor response to 131I treatment (sensitivity: 73.7 %; specificity: 69.6 %), and was also associated with worse prognosis in DM+ DTC (P< 0.001). CONCLUSION: We found CTCs ≥ 5 to be a potential predictive index for DM+ DTC; and CTCs ≥7 as a possible indicator of poor response to 131I treatment and worse prognosis in DM+ DTC.

Truncated RASSF7 promotes centrosomal defects and cell death.

RASSF7 protein localises to the centrosome and plays a key role in mitosis. Its expression is also increased in a range of tumour types. However, little is known about the molecular basis of RASSF7's function and it is not clear if it acts as an oncogene in the cancers where its levels are elevated. Here, we carry out the first analysis of the domains of rassf7, focusing on which of them are responsible for its localisation to the centrosome. Constructs were generated to allow the expression of a series of truncated versions of rassf7 and the level of centrosomal localisation shown by each protein quantified. This analysis was carried out in Xenopus embryos which are a tractable system where rassf7 localisation can easily be studied. Our data shows that the coiled-coil domain of rassf7 is required and sufficient to direct its centrosomal localisation. The RA domain did not appear to have a role in mediating localisation. Surprisingly, removal of the extreme C-terminus of the protein caused rassf7 to accumulate at the centrosome and drive centrosome defects, including accumulation of the centrosomal protein γ-tubulin and an amplification of the number of γ-tubulin foci. These effects required the centrosomal localisation mediated by the coiled-coil domain. Later in development cells expressing this truncated rassf7 protein underwent cell death. Finally, analysis of a database of tumour sequences identified a mutation in RASSF7 which would cause a similar C-terminal truncation of the protein. Based on our data this truncated protein might drive centrosomal defects and we propose the hypothesis that truncated RASSF7 could act as an oncogene in a small subset of tumours where it is mutated in this way.

A distinct serum metabolic signature of distant metastatic papillary thyroid carcinoma.

BACKGROUND: Although the incidence rate for thyroid cancer seems to have begun stabilizing in recent years, an increased rate of advanced stage of this disease has been reported. Additionally, distant metastasis is one of the most important prognostic factors of patients with papillary thyroid carcinoma (PTC). Unfortunately, the underlying mechanisms of distant metastasis, as well as cell status like metabolism changes in distant metastatic tumours have not been clearly elucidated. OBJECTIVE: To identify serum metabolic signature of distant metastatic PTC. DESIGN, PATIENTS AND MEASUREMENTS: In this study, gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS) was used to analyse the serum from 77 patients diagnosed with PTC (37 in distant metastasis group and 40 in ablation group). Principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA) scores plots were used to analyse the data. RESULTS: Principal component analysis and OPLS-DA analyses demonstrated an evident trend of separation between 40 serum samples from the ablation group and 37 samples from distant metastasis group. A total of 31 metabolites were identified, which are related to amino acid, lipid, glucose, vitamin metabolism and diet/gut microbiota interaction. Pathway analysis showed "alanine, aspartate and glutamate metabolism" and "inositol phosphate metabolism" were the most relevant pathways. CONCLUSION: Serum metabolomics profiling could significantly discriminate papillary thyroid cancer patients according to distant metastasis. Potential metabolic aberration in distant metastatic PTC could be involved in different biological behaviours of tumour cells including proliferation, invasion/migration and immune escape. Diet/gut microbiota-produced metabolites could play an important role in these effects. This work may provide new clues to find the underlying mechanisms regarding the distant metastasis of PTC as well as potential adjuvant therapy targets.

Circulating Long Non-Coding RNAs Act as Biomarkers for Predicting 131I Uptake and Mortality in Papillary Thyroid Cancer Patients with Lung Metastases.

PURPOSE: The aims of the current study were to explore plasma lncRNAs as a novel biomarker panel for the diagnosis of non-131I-avid lung metastases of PTC and to investigate the plasma lncRNA expression levels associated with survival in PTC patients with lung metastases. METHODS: The expression of lncRNAs was examined using an lncRNA microarray chip. The lncRNAs with the most significant difference in expression between PTC patients with non-131I-avid lung metastases and PTC patients with 131I-avid lung metastases were verified by quantitative reverse-transcription polymerase chain reaction. The Kaplan-Meier method was used to determine whether the plasma lncRNA levels might be indicative of patient prognosis. RESULTS: Compared with 131I-avid lung metastases, we discovered that two lncRNAs (ENST00000462717 andENST00000415582) were upregulated and two (TCONS_00024700 and NR_028494) were downregulated in the non-131I-avid lung metastases of PTC. Receiver operating characteristic curve (ROC) analyses indicated that the use of these four lncRNAs had high diagnostic sensitivity and specificity for predicting non-131I-avid lung metastases of PTC. The merged areas under the curve for ENST00000462717, ENST00000415582, TCONS_00024700,and NR_028494 in the training and validation sets were 0.890, 0.936, 0.975, and 0.918, respectively. Low (ENST00000462717 and ENST00000415582) and high plasma lncRNA levels(TCONS_00024700and NR_028494) were also found to be associated with better prognosis of PTC patients with lung metastases(P<0.001). CONCLUSIONS: ENST00000462717, ENST00000415582, TCONS_00024700, and NR_028494 may be used as novel and minimally invasive markers for the diagnosis and prognostic assessment of non-131I-avid lung metastases from PTC.

Style classification of media painting images by integrating ResNet and attention mechanism.

The progress of deep learning technology has made image classification an important application field. Image style classification is a complex task involving the recognition of the whole picture, including the recognition of salient features and detailed features. This study is based on the ResNet algorithm and has improved its Resnet 50 version with excellent performance. In the model architecture, we introduce blur pool operation and replace the traditional Relu function with Celu activation function. In addition, the triplet attention mechanism was integrated to further enhance the model performance. Through a series of experiments, it is found that the improved ResNet50 model has the highest classification accuracy of 80.6% on large-scale image data sets, which is 11.7% higher than the traditional ResNet50 model. In terms of recognition of similar style images, the model incorporating triplet attention demonstrated higher average accuracy (74%) and recall (82%). This improvement has achieved certain results and has certain technical reference value for various styles of image classification fields.