Hashimoto's thyroiditis (HT) is the most common autoimmune disease characterized by lymphocytic infiltration and thyrocyte destruction. Dissection of the interaction between the thyroidal stromal ...microenvironment and the infiltrating immune cells might lead to a better understanding of HT pathogenesis. Here we show, using single-cell RNA-sequencing, that three thyroidal stromal cell subsets, ACKR1
endothelial cells and CCL21
myofibroblasts and CCL21
fibroblasts, contribute to the thyroidal tissue microenvironment in HT. These cell types occupy distinct histological locations within the thyroid gland. Our experiments suggest that they might facilitate lymphocyte trafficking from the blood to thyroid tissues, and T cell zone CCL21
fibroblasts may also promote the formation of tertiary lymphoid organs characteristic to HT. Our study also demonstrates the presence of inflammatory macrophages and dendritic cells expressing high levels of IL-1β in the thyroid, which may contribute to thyrocyte destruction in HT patients. Our findings thus provide a deeper insight into the cellular interactions that might prompt the pathogenesis of HT.
A novel HfO2/V2O5 nanocomposite has been fabricated for use as photocatalyst. HfO2 nanoparticles (NPs) were deposited on V2O5 using a precipitation method. Both commercial V2O5 particles and ...microwave‐assisted hydrothermal (MAH)‐synthesized V2O5 nanowires (NWs) were used. We demonstrate that the HfO2/V2O5 nanocomposite exhibits better photodegradation efficiency than the V2O5. The photodegradation reaction constant of the HfO2/V2O5 nanocomposite is more than 66% higher than that of the V2O5. The wide‐bandgap, transparent HfO2 effectively reduces the electron‐hole recombination by proving defect levels to quench the recombination. A plausible band structure is proposed to support the existence of these defect levels.
The addition of wide‐bandgap HfO2 onto V2O5 reduces the electron‐hole recombination. As a result, enhanced photodegradation of methylene blue was observed in the HfO2/V2O5 composites.
In mobile social networks, next point-of-interest (POI) recommendation is a very important function that can provide personalized location-based services for mobile users. In this paper, we propose a ...recurrent neural network (RNN)-based next POI recommendation approach that considers both the location interests of similar users and contextual information (such as time, current location, and friends’ preferences). We develop a spatial-temporal topic model to describe users’ location interest, based on which we form comprehensive feature representations of user interests and contextual information. We propose a supervised RNN learning prediction model for next POI recommendation. Experiments based on real-world dataset verify the accuracy and efficiency of the proposed approach, and achieve best
F
1-score of 0.196 754 on the Gowalla dataset and 0.354 592 on the Brightkite dataset.
The mechanisms of bifurcation, a key step in thyroid development, are largely unknown. Here we find three zebrafish lines from a forward genetic screening with similar thyroid dysgenesis phenotypes ...and identify a stop-gain mutation in hgfa and two missense mutations in met by positional cloning from these zebrafish lines. The elongation of the thyroid primordium along the pharyngeal midline was dramatically disrupted in these zebrafish lines carrying a mutation in hgfa or met. Further studies show that MAPK inhibitor U0126 could mimic thyroid dysgenesis in zebrafish, and the phenotypes are rescued by overexpression of constitutively active MEK or Snail, downstream molecules of the HGF/Met pathway, in thyrocytes. Moreover, HGF promotes thyrocyte migration, which is probably mediated by downregulation of E-cadherin expression. The delayed bifurcation of the thyroid primordium is also observed in thyroid-specific Met knockout mice. Together, our findings reveal that HGF/Met is indispensable for the bifurcation of the thyroid primordium during thyroid development mediated by downregulation of E-cadherin in thyrocytes via MAPK-snail pathway.
Idiopathic pulmonary fibrosis (IPF) affects an increasing number of people globally, yet treatment options remain limited. At present, conventional treatments depending on drug therapy do not show an ...ideal effect in reversing the lung damage or extending the lives of IPF patients. In recent years, more and more attention has focused on extracellular vesicles (EVs) which show extraordinary therapeutic effects in inflammation, fibrosis disease, and tissue damage repair in many kinds of disease therapy. More importantly, EVs can be modified or used as a drug or cytokine delivery tool, targeting injury sites to enhance treatment efficiency. In light of this, the treatment strategy of mesenchymal stem cell-extracellular vesicles (MSC-EVs) targeting the pulmonary microenvironment for IPF provides a new idea for the treatment of IPF. In this review, we summarized the inflammation, immune dysregulation, and extracellular matrix microenvironment (ECM) disorders in the IPF microenvironment in order to reveal the treatment strategy of MSC-EVs targeting the pulmonary microenvironment for IPF.
The outbreak of coronavirus disease 2019 (COVID-19) has so far resulted in over a hundred million people being infected. COVID-19 poses a threat to human health around the world. Severe acute ...respiratory syndrome coronavirus 2 (SARS-CoV-2) has been confirmed as the pathogenic virus of COVID-19. SARS-CoV-2 belongs to the β-coronavirus family of viruses and is mainly transmitted through the respiratory tract. It has been proven that SARS-CoV-2 mainly targets angiotensin-converting enzyme II (ACE2) receptors on the surface of various cells in humans. The main clinical symptoms of COVID-19 include fever, cough, and severe acute respiratory distress syndrome (ARDS). Current evidence suggests that the damage caused by the virus may be closely related to the induction of cytokine storms in COVID-19. No specific drugs or measures have yet to be shown to cure COVID-19 completely. Cell-based approaches, primarily mesenchymal stem cells (MSCs), have been identified to have anti-inflammatory and immune functions in COVID-19. Clinical studies about using MSCs and its derivatives—exosomes for COVID-19 treatment—are under investigation. Here, we review the current progress of the biological characteristics, clinical manifestations, and cell-based treatment development for COVID-19. Providing up-to-date information on COVID-19 and potential MSC therapies will help highlight routes to prevent and treat the disease.
Background
Molecular testing for oncogenic mutations in fine‐needle aspiration has showed high predictive value in identifying malignant lesions from thyroid nodules with indeterminate cytology.
...Methods
To figure out an efficient and economical gene panel for most medical institutions in China, we designed a five‐gene panel including BRAF/NRAS/KRAS/HRAS/TERT genes and conducted a retrospective study to evaluate the role of this five‐gene diagnostic panel in differential diagnosis of thyroid nodules.
Results
A total of 665 patients with 695 thyroid nodules were investigated in the current study. The fine‐needle aspiration biopsy and surgically separated thyroid tissue specimens were harvested to test BRAF, TERT, NRAS, KRAS, and HRAS mutations. We identified 261 mutations in 665 patients, including 177 V600E mutations in BRAF. Three hundred and sixty‐nine patients who underwent thyroid surgery after completion of the initial clinical and cytological evaluation were enrolled in the final analysis. The diagnostic sensitivity, specificity, and accuracy of the combination of FNAB cytology and five‐gene detection were 74.7%, 93.8%, and 84.8%, respectively. BRAF V600E and five‐gene panel could recognize 46.4% and 53.6% of papillary thyroid carcinoma in the patients with cytologically indeterminate nodules.
Conclusion
The five‐gene panel can effectively improve the sensitivity, negative predictive value, and accuracy of fine‐needle aspiration biopsy cytology, especially in the patients with cytologically indeterminate nodules.
Our study focuses on the feasibility and utility of a five‐gene panel containing BRAF/RAS/TERT mutation detection in the improvement of fine‐needle aspiration biopsy (FNAB) cytology in differential diagnosis of thyroid nodules in China. Our results demonstrated that BRAF/five‐gene mutations detected in FNAB samples can effectively improve the sensitivity, negative predictive value (NPV), and accuracy of FNAB cytology, while kept the specificity and positive predictive value (PPV).
Viral advertising in social networks has arisen as one of the most promising ways to increase brand awareness and product sales. By distributing a limited budget, we can incentivize a set of users as ...initial adopters so that the advertising can start from the initial adopters and spread via sociM links to become viral. Despite extensive researches in how to target the most influential users, a key issue is often neglected： how to incentivize the initial adopters. In the problem of influence maximization, the assumption is that each user has a fixed cost for being initial adopters, while in practice, user decisions for accepting the budget to be initial adopters are often probabilistic rather than deterministic. In this paper, we study optimal budget allocation in social networks to maximize the spread of viral advertising. In particular, a concave probability model is introduced to characterize each user＇s utility for being an initial adopter. Under this model, we show that it is NP-hard to find an optimal budget allocation for maximizing the spread of viral advertising. We then present a novel discrete greedy algorithm with near optimal performance, and further propose scaling-up techniques to improve the time-efficiency of our algorithm. Extensive experiments on real-world social graphs are implemented to validate the effectiveness of our algorithm in practice. The results show that our algorithm can outperform other intuitive heuristics significantly in almost all cases.
Wireless networks are developed under the fashion of wider spectrum utilization （e.g., cognitive radio） and multi-hop communication （e.g., wireless mesh networks）. In these paradigms, how to ...effectively allocate the spectrum to different transmission links with minimized mutual interference becomes the key concern. In this paper, we study the throughput optimization via spectrum allocation in cognitive radio networks （CRNs）. The previous studies incorporate either the conflict graph or SINR model to characterize the interference relationship. However, the former model neglects the accumulative interference effect and leads to unwanted interference and sub-optimal results, while the work based on the latter model neglects its heavy reliance on the accuracy of estimated RSS （receiving signal strength） among all potential links. Both are inadequate to characterize the complex relationship between interference and throughput. To this end, by considering the feature of CRs, like spectrum diversity and non-continuous OFDM, we propose a measurement-assisted SINR-based cross-layer throughput optimization solution. Our work concerns features in different layers： in the physical layer, we present an efficient RSS estimation algorithm to improve the accuracy of the SINR model; in the upper layer, a flow level SINR-based throughput optimization problem for WMNs is modelled as a mixed integer non-linear programming problem which is proved to be NP-hard. To solve this problem, a centralized （1 -ε）-optimal algorithm and an efficient distributed algorithm are provided. To evaluate the algorithm performance, the real-world traces are used to illustrate the effectiveness of our scheme.
This study aimed to assess the commutability of frozen pooled human serum (PHS), high concentration of Immunoglobulin M (IgM) pure diluted materials (HPDM), commercialized pure materials (CPM), and ...dilutions of ERM-DA470k/IFCC in IgM detection using the CLSI and IFCC approaches, to support standardization or harmonization of IgM measurement.
Twenty-four serum samples, relevant reference materials (PHS, HPDM, CPM), and different ERM-DA470k/IFCC dilutions were analyzed in triplicate using six routine methods. The commutability of the relevant reference materials was carried out following CLSI EP30-A and IFCC bias analysis.
According to the CLSI approach, low, medium, and high concentrations of PHS, HPDM, and CPM were commutable on 10, 13, 15, 13, and 8 of 15 assay combinations, respectively. Using the IFCC approach, low, medium, and high concentrations of PHS, HPDM, and CPM were commutable on 10, 11, 9, 15, and 10 of 15 assay combinations, respectively. The ERM-DA470k/IFCC dilutions with D-PBS and RPMI-1640 Medium were commutable on 13 of 15 assay combinations according to CLSI and were commutable on all 15 assay combinations using IFCC approach.
High concentration of PHS were commutable on all six detection systems using the CLSI approach. Low and medium concentration of PHS showed unsatisfied commutability. HPDM, not CPM have good commutability, has the potential to become reference materials. ERM-DA470k/IFCC diluted with different medium showed different commutability.
PDF
