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Background: As a critical component of exosomes, circular RNAs (circRNAs) have shown great value in cancer diagnosis. This study aimed to identify circRNAs in exosomes for the diagnosis of PTC (papillary thyroid carcinoma). Methods: We selected hsa_circ_0082002 and hsa_circ_0003863 based on circRNA microarray. The levels of exosomal hsa_circ_0082002 and hsa_circ_0003863 in the sera of healthy control (n = 68), benign thyroid tumors (n = 60), and PTC without and with Hashimoto's thyroiditis (n = 164) were quantified by qPCR (quantitative polymerase chain reaction). Receiver operating characteristic analyses were conducted to evaluate the diagnostic sensitivity and specificity. Bioinformatics databases were used to predict the microRNAs and proteins binding with hsa_circ_0082002 and hsa_circ_0003863. Results: The levels of exosomal hsa_circ_0082002 and hsa_circ_0003863 were positively associated and statistically increased in PTC compared to healthy and benign thyroid tumors. Intriguingly, higher levels of exosomal hsa_circ_0082002 and hsa_circ_0003863 were positively correlated with lymph node metastasis and vascular invasion in PTC. Further stability tests show that exosomal hsa_circ_0082002 and hsa_circ_0003863 could exist stably in sera treated by several freeze–thaw cycles at -20 °C and with a storage time shorter than 24 h at 4 °C. Furthermore, hsa_circ_0082002 and hsa_circ_0003863 were predicted to interact with microRNAs and proteins, suggesting that hsa_circ_0082002 and hsa_circ_0003863 might contribute to the occurrence and progression of PTC through interacting with microRNAs and RNA binding proteins. Conclusion: Collectively, we identified two PTC-related circRNAs incorporated in exosomes and uncovered their potential as tumor markers to diagnose PTC, in particular, more aggressive PTC. [ABSTRACT FROM AUTHOR]

Cholesterol biosynthesis and metabolism are critical aspects that shape the process of tumor development and associated microenvironmental conditions owing to the ability of cholesterol to drive tumor growth and invasion. Squalene Epoxidase (SQLE) is the second rate-limiting enzyme involved in the synthesis of cholesterol. The functional role of SQLE within the tumor microenvironment, however, has yet to be established. Here we show that SQLE is distinctively expressed across most types of cancer, and the expression level is highly correlated with tumor mutation burden and microsatellite instability. Accordingly, SQLE was identified as a prognostic risk factor in cancer patients. In addition, we observed a negative correlation between SQLE expression and immune cell infiltration across multiple cancers, and murine xenograft model further confirmed that SQLE knockdown was associated with enhanced intratumoral CD8+ T cell infiltration. Using next-generation sequencing, we identified 410 genes distinctively expressed in tumors exhibiting SQLE inhibition. KEGG and GO analysis further verified that SQLE altered the immune response in the tumor microenvironment. Furthermore, we found that the metabolism and translation of proteins is the main binding factor with SQLE. Our findings ascertain that SQLE is a potential target in multiple cancers and suppressing SQLE establishes an essential mechanism for shaping tumor microenvironment. • (1) SQLE may serve as a promising biomarker for the diagnosis, treatment, and prognosis of human cancers. • (2) Knockdown SQLE inhibits melanoma growth by elevating CD8+ cytotoxic T cell accumulation. • (3) Protein-protein interactions exist between SQLE and EIF3D. [ABSTRACT FROM AUTHOR]

Polyarylene ether nitrile sulfone (PENS) random copolymers consisting of polyarylene ether nitrile (PEN) and polyarylene ether sulfone (PES) were prepared from bisphenol A, bis(4-chlorophenyl)sulfone, and 2,6-dichlorobenzonitrile by the nucleophilic aromatic substitution polymerization. The structure of the PENS random copolymers was confirmed by Fourier transform infrared spectrometer and 1H nuclear magnetic resonance, and the properties of the PENS copolymers were investigated by thermal analysis (differential scanning calorimetry and thermogravimetric analysis), inherent viscosity measurements, mechanical tests, and dielectric tests. The samples showed excellent thermal stability, with the 5% weight loss temperature (T 5%) greater than 480°C under nitrogen and glass transition temperature (T g) greater than 180°C. The tensile strength, tensile modulus, and elongation at break of the PENS copolymers were improved with the increase of the PEN content, indicating the better mechanical property of PEN than that of PES. The dielectric constant and dielectric strength of the PENS random copolymers were also enhanced with the increase of the PEN content. As a result, PENS100 showed the highest energy storage density, which is 0.68 J/cm3. PES showed better thermal properties while worse mechanical and dielectric properties compared with PEN. PENS copolymers combined the excellent properties of PEN and PES due to the compatibility between them. [ABSTRACT FROM AUTHOR]

H1N1, one of the most prevalent influenza A virus subtypes affecting the human population, can cause infections varying from mild respiratory syndrome to severe pneumonia. The current H1N1 vaccine needs to be updated annually and does not protect against future outbreaks. Here, we downloaded 2,656 HA protein sequences of human H1N1 viruses from the NCBI influenza database (up to the date of Aug. 2012) and constructed a phylogenetic tree of these H1 proteins via the neighbor-joining method using MEGA 5.0 software. A consensus H1 protein (CH1) was generated and was further modified with published conserved T-cell and B-cell epitopes. Interestingly, this CH1 protein is genetically similar to an H1 isolate obtained during the 1980s (A/Memphis/7/1980), indicating that a universal HA antigen may exist in nature. Vaccination with a DNA vaccine expressing CH1 elicited broadly reactive T-cell and B-cell responses to heterologous H1N1 viruses, though this vaccine did not successfully neutralize pdm09 H1N1 viruses. A combination of CH1 and pdm09 HA in a DNA vaccination neutralized pdm09 H1N1 viruses and protected mice from lethal infections by all representative H1N1 viruses. Moreover, a recombinant chimeric PR8-CH1 virus carrying HA sequence of the consensus H1 and all other seven genes from the PR8 strain was highly attenuated in mice, with a lethal dose (LD 50 ) of more than 10 6 pfu. Vaccination with PR8-CH1 virus provided complete protection against infections by heterologous H1N1 strains. Taken together, a universal H1 antigen, CH1, was developed by constructing a consensus HA sequence, and the PR8-CH1 virus containing this consensus sequence elicited broadly protective immunity against heterologous H1N1 viruses. [ABSTRACT FROM AUTHOR]

A cell culture-based vaccine production system is preferred for the large-scale production of influenza vaccines and has advantages for generating vaccines against highly pathogenic influenza A viruses. Vero cells have been widely used in human vaccine manufacturing, and the safety of these cells has been well demonstrated. However, the most commonly used influenza-vaccine donor virus, A/Puerto Rico/8/1934 (PR8) virus, does not grow efficiently in Vero cells. Therefore, we adapted the PR8 virus to Vero cells by continuous passaging, and a high-growth strain was obtained after 20 passages. Sequence analysis and virological assays of the adapted strain revealed that mutations in four viral internal genes (NP, PB1, PA and NS1) were sufficient for adaptation. The recombinant virus harboring these mutations (PR8-4mut) displayed accelerated viral transport into the nucleus and increased RNP activity. Importantly, the PR8-4mut could serve as a backbone donor virus to support the growth of the H7N1, H9N2 and H5N1 avian viruses and the H1N1 and H3N2 human viruses in Vero cells without changing its pathogenicity in either chicken embryos or mice. Thus, our work describes the generation of a Vero-adapted, high-yield PR8-4mut virus that may serve as a promising candidate for an influenza-vaccine donor virus. [ABSTRACT FROM AUTHOR]

Abstract: Whether the 2009 pandemic H1N1 influenza vaccine can induce heterosubtypic cross-protective anti-hemagglutinin (HA) neutralizing antibodies is an important issue. We obtained a panel of fully human monoclonal antibodies from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Most of the monoclonal antibodies targeted the HA protein but not the HA1 fragment. Among the analyzed antibodies, seven mAbs exhibited neutralizing activity against several influenza A viruses of different subtypes. The conserved linear epitope targeted by the neutralizing mAbs (FIEGGWTGMVDGWYGYHH) is part of the fusion peptide on HA2. Our work suggests that a heterosubtypic neutralizing antibody response primarily targeting the HA stem region exists in recipients of the 2009 pandemic H1N1 influenza vaccine. The HA stem region contains various conserved neutralizing epitopes with the fusion peptide as an important one. This work may aid in the design of a universal influenza A virus vaccine. [Copyright &y& Elsevier]

Radiotherapy benefits patients with advanced esophageal squamous cell carcinoma (ESCC) in terms of symptom relief and long-term survival. In contrast, a substantial proportion of ESCC patients have not benefited from radiotherapy. This study aimed to establish and validate an artificial neural network-based radiomics model for the pretreatment prediction of the radiotherapy response of advanced ESCC by using integrated data combined with feasible baseline characteristics of computed tomography. A total of 248 patients with advanced ESCC who underwent baseline CT and received radiotherapy were enrolled in this study and were analyzed by two types of radiomics models, machine learning and deep learning. As a result, the Att. Resnet50 pretrained network model indicated superior performance, with AUCs of 0.876, 0.802 and 0.732 in the training, internal validation, and external validation cohorts, respectively. Similarly, our Att. Resnet50 pretrained network model showed excellent calibration and significant clinical benefit according to the C index and decision curve analysis. Herein, a novel pretreatment radiomics model was established based on deep learning methods and could be used for radiotherapy response prediction in advanced ESCC patients, thus providing reliable evidence for therapeutic decision-making. [ABSTRACT FROM AUTHOR]

Deubiquitinase ubiquitin-specific protease 11 (USP11), a member of the deubiquitinating family, plays an important but still controversial role in cancer development. Namely, USP11 has been shown to promote the proliferation and metastasis of hepatocellular carcinoma (HCC), but the underlying molecular basis is poorly understood. This study aimed to unravel novel functions of USP11 in HCC, especially those related to autophagy. Here, EdU, migration and colony formation assays, and mouse models showed that USP11 played a crucial role in HCC cell proliferation and metastasis in vitro and in vivo. Results from co-immunoprecipitation and ubiquitination assays demonstrated that USP11 interacted with E2F1 and maintained E2F1 protein stability by removing its ubiquitin. Notably, E2F1 regulated USP11 expression at the transcriptional level. Thus, the E2F1/USP11 formed a positive feedback loop to promote the proliferation and migration of HCC cells. Moreover, E2F1/USP11 inhibited autophagy by regulating ERK/mTOR pathway. In addition, the combination treatment inhibition of USP11 and autophagy enhanced the apoptosis of HCC cells and inhibited the tumor growth in mice more effective than either treatment alone. Taken together, these results indicate that the E2F1/USP11 signal axis promotes HCC proliferation and metastasis and inhibits autophagy, which provides an experimental basis for the treatment of HCC. [ABSTRACT FROM AUTHOR]

During photothermal therapy (PTT), hyperthermia up to 50 °C is required for efficient induction of tumor cell death. Additional increases in temperature can lead to severe damage to adjacent tissues. Conversely, insufficient heating of deep‐seated tumor tissues results in tumor recurrence. Sensitization of tumor cells to PTT may solve this problem. Stress granules (SGs) function in integration of various internal and external stresses to regulate cell viability. However, the role of SGs in PTT is currently unknown. Here, with black phosphorus (BP) nanosheets as photothermal agents, it is found that SGs are induced in tumor by PTT through eukaryotic initiation factor 2α‐dependent pathway and participate in tumor resistance to PTT. To modulate SG formation in tumor, a BP hydrogel is prepared for tumor‐specific delivery and near‐infrared (NIR) light‐controlled release of the SG inhibitor Emetine. Upon NIR‐light irradiation, photothermal conversion of BP nanosheets enables PTT of tumor. Meanwhile, light‐controlled release of Emetine in tumor tissues effectively inhibits PTT‐induced SG formation and sensitizes tumor to PTT, resulting in enhanced tumor inhibition. These results reveal the role of SGs in PTT and present a novel strategy for tumor sensitization to enhance the therapeutic efficacy and reduce the side effects of PTT. [ABSTRACT FROM AUTHOR]

Metallopolymeric superstructures (MPS) are hybrid functional materials that find wide applications in environmental, energy, catalytic and biomedical-related scenarios, while their fabrication usually suffers from the complicated polymerization between monomeric ligands and metal ions. In this work, we have developed a facile one-step protocol to fabricate metallopolymeric superstructures with different morphology including nanospheres, nanocubes, nanorods, and nanostars for environmental remediation application. Specifically, we have firstly synthesized the amphiphilic block copolymers (BCP) bearing hydrophobic aromatic backbone and hydrophilic pendent carboxylic/sulfonic groups, which have been subsequently transformed into MPS via the metal ions mediated self-assembly in mixed solution of dimethylformamide (DMF) and H2O. Based on SEM, FTIR, XRD and XPS characterization, we have revealed that the fine morphology and condensed structures of MPS can be modulated via the metal ions and BCP concentration, and the obtained MPS can be employed as efficient adsorbents for the removal of methylene blue with maximum adsorption capacity approaching 936.13 mg/g. [ABSTRACT FROM AUTHOR]

Poly(arylene ether nitrile) (PEN) copolymers (HQ/RS-PEN) containing different proportions of hydroquinone (HQ-PEN) block and resorcinol (RS-PEN) block were synthesized, and their crystalline, mechanical, and dielectric properties were investigated. Three HQ/RS-PEN copolymers with 10%, 20%, and 30% of RS-PEN blocks were prepared via condensation polymerization of HQ and RS with 2,6-dichlorobenzonitrile. The PEN copolymers were characterized and confirmed by Fourier transform infrared spectroscopy, intrinsic viscosity, and thermal analyses. With the addition of RS-PEN block, the flexibility of PEN copolymers was increased. In addition, even though the high loading content of RS-PEN block was incorporated, the PEN copolymers still exhibited relatively high dielectric constant, whereas the dielectric loss decreased. Furthermore, to investigate the effect of treatment time and temperature on the physical properties of crystalline PEN copolymers, HQ/RS-PEN20 was isothermally treated at different temperatures (280°C, 300°C, 310°C, 320°C, and 330°C) for a constant time and at a constant time for different hours (1, 2, 3, 4, and 5 h). After the optimization of the crystallization of HQ/RS-PEN polymer, excellent mechanical and dielectric properties of copolymers were obtained. The results showed that when isothermally treated at 320°C for 2 h, the HQ/RS-PEN20 showed optimal properties of tensile strength of 117.6 MPa and dielectric constant of 4.07 at 1 kHz. [ABSTRACT FROM AUTHOR]

Radiotherapy is the standard adjuvant treatment for esophageal squamous cell carcinoma (ESCC), yet radioresistance remains a major obstacle leading to treatment failure and unfavorable prognosis. Previous reports have demonstrated the involvement of astrocyte elevated gene-1 (AEG-1) in tumorigenesis and progression of multiple malignancies. Nevertheless, the precise role of AEG-1 in the radioresistance of ESCC remains elusive. Here, we unveiled a strong correlation between aberrant AEG-1 gene overexpression and malignant progression as well as adverse prognosis in ESCC patients. Moreover, both in vitro and in vivo investigations revealed that AEG-1 significantly alleviated irradiation-induced DNA damage and enhanced radiation resistance in ESCC cells. Mechanistically, AEG-1 recruited the deubiquitinase USP10 to remove the K48-linked polyubiquitin chains at the Lys425 of PARP1, thus preventing its proteasomal degradation. This orchestrated process facilitated homologous recombination-mediated DNA double-strand breaks (DSBs) repair, culminating in mitigated DNA damage and acquired radioresistance in ESCC cells. Notably, PARP1 overexpression reversed the radiosensitizing effect caused by AEG-1 deficiency. Collectively, these findings shed new light on the mechanism of ESCC radioresistance, providing potential therapeutic targets to enhance the efficacy of radiotherapy in ESCC. • High expression level of AEG-1 is associated with poor prognosis in ESCC. • AEG-1 alleviates irradiation-induced DNA damage and confers radioresistance in ESCC cells both in vitro and in vivo. • AEG-1 promotes the homologous recombination-mediated repair of irradiation-induced DNA double-strand breaks. • AEG-1 recruits USP10 to remove the K48-linked polyubiquitin chains at the Lys425 site of PARP1 to prevent its degradation. [ABSTRACT FROM AUTHOR]

Lanthanide coordinating polymeric microparticles are considered as versatile building blocks for construction of various advanced functional materials and devices, but the research involving the modulation of their fine morphology, luminescence properties and processability is still limited. Herein, we have synthesized an amphiphilic aromatic multi-block copolymer (abbreviated as amPENS) showing intrinsic blue fluorescence emission, which was further employed as a coordination ligand to sensitize the intrinsic fluorescence emission of Tb3+ and Eu3+. Specifically, the three dimensional (3D) emulsion confinement self-assembly of amPENS with lanthanide ions was explored to fabricate sub-micron sized Ln-PENS microparticles, whose fluorescence emission and surface morphology can be readily tuned via the concentration of amPENS and lanthanide ions, as well as stirring speed during emulsion self-assembly. More importantly, we further proved that the Ln-PENS doped polyvinyl alcohol (PVA) solution can be processed into multi-band emissive fluorescent nanofibers coatings via electrospinning. Basically, the current work reveals a new strategy to design lanthanide coordination polymeric superparticles with tunable morphology and fluorescence, which would open the way for fabrication of advanced lanthanide based materials for various applications such as sensing, anti-counterfeiting, information recording and optoelectric devices. [Display omitted] • An amphiphilic multi-block aromatic copolymer (named as amPENS) were synthesized. •AmPENS was used as ligand to sensitize the fluorescence of lanthanide Tb3+ and Eu3+. •Emulsion confinement self-assembly of amPENS with Tb3+ or Eu3+ was studied in detail. •Lanthanide coordinated amPENS (Ln-PENS) fluorescence microparticles were prepared. •Ln-PENS microparticles were converted to fluorescent nanofibers via electrospinning. [ABSTRACT FROM AUTHOR]

Self-assembly of block copolymer is a well-known methodology to fabricate soft functional nanostructures. Herein, the block copolymers containing both rigid aromatic moieties and flexible ether groups in the backbone, named of co -polyarylene ether nitriles, have been synthesized and further transformed into metal coordination polymeric microspheres (MCPMS) via the Pb2+ mediated self-assembly occurring in confined emulsion droplet. Based on the systematic characterization of SEM, TEM, SAED, XRD and XPS, it is found that the size, morphology, aggregate structure as well as fluorescent properties of obtained MCPMS can be readily modulated by tuning of block copolymer backbone structures and self-assembly parameters. More interestingly, the obtained MCPMS can be further employed as robust templates for in-situ immobilization of silver nanoparticles. Therefore, the metal ions assisted self-assembly of aromatic block copolymer in emulsion droplets reported in this work basically open a new way for fabrication of functional hybrid nanomaterials. Image 1 • Rod-coil amphiphilic block copolymer named of amPEN has been synthesized. • AmPEN has been self-assembled into microspheres via emulsion solvent evaporation. • Crystallized metal coordination polymeric microspheres (MCPMS) are obtained. • MCPMS are fabricated by introducing Pb2+ into emulsion solvent evaporation of amPEN. • MCPMS can be used as robust templates for in-situ synthesis of silver nanoparticles. [ABSTRACT FROM AUTHOR]