Search

Atherosclerotic plaques form in the inner layer of arteries triggering heart attacks and strokes. Although T cells have been detected in atherosclerosis, tolerance dysfunction as a disease driver remains unexplored. Here we examine tolerance checkpoints in atherosclerotic plaques, artery tertiary lymphoid organs and lymph nodes in mice burdened by advanced atherosclerosis, via single-cell RNA sequencing paired with T cell antigen receptor sequencing. Complex patterns of deteriorating peripheral T cell tolerance were observed being most pronounced in plaques followed by artery tertiary lymphoid organs, lymph nodes and blood. Affected checkpoints included clonal expansion of CD4+, CD8+ and regulatory T cells; aberrant tolerance-regulating transcripts of clonally expanded T cells; T cell exhaustion; Treg–TH17 T cell conversion; and dysfunctional antigen presentation. Moreover, single-cell RNA-sequencing profiles of human plaques revealed that the CD8+ T cell tolerance dysfunction observed in mouse plaques was shared in human coronary and carotid artery plaques. Thus, our data support the concept of atherosclerosis as a bona fide T cell autoimmune disease targeting the arterial wall.

A single digital newsletter usually contains many messages (regions). Users' reading time spent on, and read level (skip/skim/read-in-detail) of each message is important for platforms to understand their users' interests, personalize their contents, and make recommendations. Based on accurate but expensive-to-collect eyetracker-recorded data, we built models that predict per-region reading time based on easy-to-collect Javascript browser tracking data. With eye-tracking, we collected 200k ground-truth datapoints on participants reading news on browsers. Then we trained machine learning and deep learning models to predict message-level reading time based on user interactions like mouse position, scrolling, and clicking. We reached 27\% percentage error in reading time estimation with a two-tower neural network based on user interactions only, against the eye-tracking ground truth data, while the heuristic baselines have around 46\% percentage error. We also discovered the benefits of replacing per-session models with per-timestamp models, and adding user pattern features. We concluded with suggestions on developing message-level reading estimation techniques based on available data., Ruoyan Kong, Ruixuan Sun, Charles Chuankai Zhang, Chen Chen, Sneha Patri, Gayathri Gajjela, and Joseph A. Konstan. Getting the most from eyetracking: User-interaction based reading region estimation dataset and models. In Proceedings of the 2023 Symposium on Eye Tracking Research and Applications, ETRA 23, New York, NY, USA, 2023. Association for Computing Machinery

Structured data peer production (SDPP) platforms like Wikidata play an important role in knowledge production. Compared to traditional peer production platforms like Wikipedia, Wikidata data is more structured and intended to be used by machines, not (directly) by people; end-user interactions with Wikidata often happen through intermediary "invisible machines." Given this distinction, we wanted to understand Wikidata contributor motivations and how they are affected by usage invisibility caused by the machine intermediaries. Through an inductive thematic analysis of 15 interviews, we find that: (i) Wikidata editors take on two archetypes---Architects who define the ontological infrastructure of Wikidata, and Masons who build the database through data entry and editing; (ii) the structured nature of Wikidata reveals novel editor motivations, such as an innate drive for organizational work; (iii) most Wikidata editors have little understanding of how their contributions are used, which may demotivate some. We synthesize these insights to help guide the future design of SDPP platforms in supporting the engagement of different types of editors.

Bulk email is often used in organizations to communicate ``important-to-organization'' messages such as policy changes, organizational plans, and administrative updates. However, normal employees may prefer messages more relevant to their jobs or interests. Organizations face the challenge of balancing prioritizing the messages they prefer employees to know (tactical goals) while maintaining employees' positive experiences with these bulk emails, then they continue to read these emails in the future (strategic goals). Could personalization help organizations achieve these tactical and strategic goals? In an 8-week field experiment with a university newsletter, we implemented a 4x5x5 factorial design on personalizing subject lines, top news, and message order based on both the employees' and the organization's preferences. We measured these designs' influences on the open/interest/recognition/read-in-detail rate of the whole newsletter and the single messages within it. We found that ``important-to-organization'' messages only got higher recognition rates when being put on subject lines / top news (tactical goal). Mixing them with employee-preferred messages in top news did not bring further improvement to their own recognition rates but could improve the whole newsletter's recognition rate. Only when the top news solely contained the employee-preferred messages were the employees slightly more interested in the newsletter (strategic goal). We further analyze on which topics the employees and the organization's preferences conflicted. Finally, we discuss the design suggestions on personalization and recommendation for organizational bulk email., This is a pre-print version of a paper accepted to CSCW 2022, The 25th ACM Conference On Computer-Supported Cooperative Work And Social Computing; Ruoyan Kong et al. 2022. Multi-Objective Personalization in Multi-Stakeholder Organizational Bulk E-mail: A Field Experiment. Proc. ACM Hum.-Comput. Interact. 6, CSCW2, Article 528 (November 2022)

Disruption of endothelial cell (ECs) and pericytes interactions results in vascular leakage in acute lung injury (ALI). However, molecular signals mediating EC–pericyte crosstalk have not been systemically investigated, and whether targeting such crosstalk could be adopted to combat ALI remains elusive. Using comparative genome-wide EC–pericyte crosstalk analysis of healthy and LPS-challenged lungs, we discovered that crosstalk between endothelial nitric oxide and pericyte soluble guanylate cyclase (NO–sGC) is impaired in ALI. Indeed, stimulating the NO–sGC pathway promotes vascular integrity and reduces lung edema and inflammation-induced lung injury, while pericyte-specific sGC knockout abolishes this protective effect. Mechanistically, sGC activation suppresses cytoskeleton rearrangement in pericytes through inhibiting VASP-dependent F-actin formation and MRTFA/SRF-dependent de novo synthesis of genes associated with cytoskeleton rearrangement, thereby leading to the stabilization of EC–pericyte interactions. Collectively, our data demonstrate that impaired NO–sGC crosstalk in the vascular niche results in elevated vascular permeability, and pharmacological activation of this crosstalk represents a promising translational therapy for ALI.

Ruminal acidosis often occurs in production, which greatly affects animal health and production efficiency. Subacute rumen acidosis (SARA) occurs when rumen pH drops rapidly to 5.5–5.8, and acute rumen acidosis (ARA) occurs when rumen pH drops below 5.0, but the molecular regulation mechanism of the rumen epithelium after the rapid decrease in pH is still unclear. Bovine rumen epithelial cells (BRECs) were cultured at pH = 7.4 (control), 5.5 (SARA), and 4.5 (ARA). Transcriptome and metabolomic methods were used to obtain the molecular-based response of BRECs to different pH treatments; pH = 4.5 can significantly induce apoptosis of BRECs. The RNA-seq experiments revealed 1381 differently expressed genes (DEGs) in the control vs. SARA groups (p < 0.05). Fibroblast growth factor (FGF) and tumor necrosis factor (TNF) were upregulated 4.25 and 6.86 fold, respectively, and TLR4 was downregulated 0.58 fold. In addition, 283 DEGs were identified in the control vs. ARA comparison (p < 0.05), and prostaglandin-endoperoxide synthase 2 (PSTG2) was downregulated 0.54 fold. Our research reveals that the MAPK/TNF signaling pathway regulates the inflammatory response of BRECs. Metabolomics identified 35 biochemical compounds that were significantly affected (p < 0.05) in control vs. SARA and 51 in control vs. ARA. Bioinformatics analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database revealed that drug metabolism-cytochrome P450 metabolic and alpha-linolenic acid metabolism changes occurred. These transcriptional and metabolic changes are related to the adaptation of BRECs to low-pH stresses. In conclusion, the combined data analyses presented a worthy strategy to characterize the cellular, transcriptomic, and metabonomic adaptation of BRECs to pH in vitro. We demonstrated transcriptional expression changes in BRECs under pH stress and activation of the molecular mechanisms controlling inflammation.

Although many researches have explored the prognostic factors associated with length of hospital stay (LOS) of adult burn patients, fewer reports concerning pediatric burn patients have been conducted. The present study employed pediatric burn data to identify factors related to LOS and developed a novel model to assess the possibility of requiring surgery. A total of 750 children admitted for burns met the criteria for enrollment. We have analyzed the medical records using multivariable linear regression and logistic regression. The pediatric patients were stratified into medical (nonsurgical) and surgical groups, respectively. The median LOS was 27.11 ± 17.91 days (range: 6–107 days). Following multiple linear regression, surgery (P < .001; 95% confidence interval [CI]: 6.485, 11.918), percent total BSA (%TBSA) (P < .001; 95% CI: 0.271, 0.459), days to surgery (P < .001; 95% CI: 0.349, 0.648), etiology (P < .001; 95% CI: −15.801, −9.422), infection (P < .001; 95% CI: 4.163, 8.329), and erythrocyte loss (P < .001; 95% CI: 1.923, 4.017) were significantly associated with LOS. After logistic regression, the percent full thickness (%FT) (P < .001; odds ratio [OR]: 2.358; 95% CI: 1.680, 3.311), infection (P < .001; OR: 2.935; 95% CI: 2.014, 4.278), and erythrocyte loss (P < .001; OR: 0.572; 95% CI: 0.470, 0.696) within 5 days postadmission were independently related to the probability of requiring surgery. In conclusion, in pediatric patients admitted with burn size of TBSA ≥20%, factors independently influencing LOS were surgery, %TBSA, days to surgery, etiology, erythrocyte loss, and infection. Furthermore, the pivotal predictors of probability requiring surgery were %FT, infection, and erythrocyte loss.

Objective To investigate the efficacy and safety of simultaneous subxiphoid single-port thoracoscopic resection of bilateral lung lesions. Methods This retrospective study analyzed the clinical data of 72 patients who underwent resection of bilateral lung lesions at the Department of Thoracic Surgery in the First Affiliated Hospital of University of Science and Technology of China between August 2020 and January 2022. Surgery-related parameters were compared between patients who underwent subxiphoid single-port thoracoscopy (subxiphoid group, 36 patients) and patients who underwent intercostal single-port thoracoscopy (intercostal group, 36 patients). Results Compared to the intercostal group, the subxiphoid group exhibited significantly better postoperative catheterization time (P = 0.013), postoperative thoracic drainage, postoperative visual analog scale pain scores at 24 and 48 h, and incision pain and numbness at 1 and 3 months after surgery (all P P > 0.05). There were no cases of perioperative mortality, conversion to thoracotomy, or serious complications in either group. Conclusion Subxiphoid single-port thoracoscopic surgery for simultaneous resection of bilateral lung lesions is safe and effective, reduces postoperative acute and chronic pain, decreases trauma, allows faster recovery, and is more consistent with the concept of minimally invasive surgery than bilateral intercostal single-port thoracoscopy. Thus, this subxiphoid single-port thoracoscopic surgery approach should be considered for clinical application.

Although various pro- and anti-inflammatory T cell subsets have been observed in murine and human atherosclerosis, principal issues of T cell immunity remain unanswered: Is atherosclerosis progression critically affected by aberrant T cell responses? Are tolerance checkpoints compromised during atherosclerosis progression? Answers to these questions will determine if we are at the cusp of developing T cell-dependent therapeutic strategies. Rapid advances in single cell RNA sequencing (scRNA-seq) and single cell α/β T cell receptor (TCR) (scTCR) sequencing allows to address these issues in unprecedented ways. The majority of T cells recognize peptide antigen-MHC complexes presented by antigen-presenting cells which, in turn, trigger activation and proliferation (clonal expansion) of cognate TCR-carrying T cells. Thus, clonal expansion and their corresponding transcriptome are two similarly important sides of T cell immunity and both will-as hypothesized-affect the outcome of atherosclerosis. Here, we combined scRNA-seq and scTCR-seq in single cells. Moreover, we provide single T cell transcriptomes and TCR maps of three important tissues involved in atherosclerosis This approach is anticipated to address principal questions concerning atherosclerosis autoimmunity that are likely to pave the long sought way to T cell-dependent therapeutic approaches.

A major goal of methodologies related to large scale gene expression analyses is to initiate comprehensive information on transcript signatures in single cells within the tissue's anatomy. Until now, this could be achieved in a stepwise experimental approach: (1) identify the majority of transcripts in a single cell (single cell transcriptome); (2) provide information on transcripts on multiple cell subtypes in a complex sample (cell heterogeneity); and (3) give information on each cell's spatial location within the tissue (zonation transcriptomics). Such genetic information will allow construction of functionally relevant gene expression maps of single cells of a given anatomically defined tissue compartment and thus pave the way for subsequent analyses, including their epigenetic modifications. Until today these aims have not been achieved in the area of cardiovascular disease research though steps toward these goals become apparent: laser capture microdissection (LCM)-based mRNA expression microarrays of atherosclerotic plaques were applied to gain information on local gene expression changes during disease progression, providing limited spatial resolution. Moreover, while LCM-derived tissue RNA extracts have been shown to be highly sensitive and covers a range of 10-16,000 genes per array/small amount of RNA, its original promise to isolate single cells from a tissue section turned out not to be practicable because of the inherent contamination of the cell's RNA of interest with RNA from neighboring cells. Many shortcomings of LCM-based analyses have been overcome using single-cell RNA sequencing (scRNA-seq) technologies though scRNA-seq also has several limitations including low numbers of transcripts/cell and the complete loss of spatial information. Here, we describe a protocol toward combining advantages of both techniques while avoiding their flaws.

Although various pro- and anti-inflammatory T cell subsets have been observed in murine and human atherosclerosis, principal issues of T cell immunity remain unanswered: Is atherosclerosis progression critically affected by aberrant T cell responses? Are tolerance checkpoints compromised during atherosclerosis progression? Answers to these questions will determine if we are at the cusp of developing T cell-dependent therapeutic strategies. Rapid advances in single cell RNA sequencing (scRNA-seq) and single cell α/β T cell receptor (TCR) (scTCR) sequencing allows to address these issues in unprecedented ways. The majority of T cells recognize peptide antigen-MHC complexes presented by antigen-presenting cells which, in turn, trigger activation and proliferation (clonal expansion) of cognate TCR-carrying T cells. Thus, clonal expansion and their corresponding transcriptome are two similarly important sides of T cell immunity and both will-as hypothesized-affect the outcome of atherosclerosis. Here, we combined scRNA-seq and scTCR-seq in single cells. Moreover, we provide single T cell transcriptomes and TCR maps of three important tissues involved in atherosclerosis This approach is anticipated to address principal questions concerning atherosclerosis autoimmunity that are likely to pave the long sought way to T cell-dependent therapeutic approaches.

Much prior research has found gender bias in peer production systems like Wikipedia and OpenStreetMap. This bias affects both women’s participation in these platforms and content about women on these platforms. We investigated the gender content gap in Wikidata, where less than 22% of items that represent people are about women. We asked: what is the source of this bias? Specifically, does it originate from the actions of Wikidata editors or from external factors; that is, does it simply reflect existing real world gender bias? We conducted a quantitative case study that found: (i) the most popular categories of people included in Wikidata represent male-dominant professions, such as American football; (ii) within a selected set of professions where we could obtain gender distribution data, Wikidata is no more biased than the real world: men and women are included at similar percentages, and the quality of items representing men and women also is similar. We provide possible explanations for our findings and implications for addressing the Wikidata content gap.

The working environment of contemporary mechanical products is becoming more complex, and the working conditions are becoming more extreme. This has led to a significant increase in the frequency of problems in mechanical products. In order to reduce the frequency of human repair after problems, the application of the self-recovery concept has become a hot research topic in the area of smart design. However, the current application of the self-recovery concept is mostly limited to the structural and parametric levels, with less research at the functional level, which may lead to a waste of resources within products. To solve this problem, this research combines the functional-level product research method with the self-recovery concept and establishes a design process model of complex products under functional self-recovery. This model extends the application scope of the self-recovery concept and improves the efficiency of resource utilization in the product. The design process model has six steps. First, according to the user requirements and the existing product, the initial function solving is carried out, and the initial function model of the product is established. Next, the main functions of the product are determined based on the initial function model of the product. Then, according to the determined main functions of the product, combined with the parameters marked in the function structure, the self-diagnosis function is designed. After that, the LT matrix and effect library are used to design the self-regulation function corresponding to the main functions, and the parameters are used to screen the self-regulation function design scheme. Finally, according to the design scheme of the self-diagnosis function and self-regulation function, the functional period oriented to self-recovery is constructed to ensure the realization of the main functions of the product. The effectiveness of the design process model is proved through the design process of an intelligent photovoltaic power generation system at the end of the paper.

IntroductionSegmentectomy is widely used for early-stage lung cancer presenting as single or multiple ground-glass opacities (GGOs). Precise segmentectomy is the recommended procedure in China. However, clinically, most routine segmentectomies are performed using only high-resolution computed tomography (CT). The aim of this study was to evaluate the effect of two segmentectomy approaches for GGOs in the lung.MethodsFrom January 2020 to September 2020, 55 precise segmentectomies performed with real-time guidance using 3D reconstruction and 343 routine segmentectomies for patients with single or multiple GGOs were performed as uniportal procedures. To reduce bias related to outcomes, preoperative clinical factors were used for propensity score matching (1:1); 55 precision and 55 routine segmentectomies were selected and further analyzed. Perioperative outcomes, namely operation time, blood loss, resection margins, number of removed lymph nodes, postoperative pulmonary function (1 month after surgery), length of postoperative stay, and postoperative complications were compared between the two groups.ResultsPatients constituted 43 men and 67 women, with an age range of 25–68 years (median: 53 years). No significant differences were seen between the groups regarding blood loss, complications, histological type, and postoperative pulmonary function, and there were no 30-day postoperative deaths in either group. The median operation time for the Precision group (74 min) was longer than in the Routine group (55 min) (p <0.01), and the number of removed lymph nodes in the Precision group (5 ± 1.1) was higher than in the Routine group (3 ± 0.8) (p <0.01). Chest tube duration days and postoperative stay days were similar in both groups; however, the rate of air leakage on postoperative day 1 was higher in the Precision group (p = 0.020). All patients in the Precision group had adequate resection margins. Four patients (7.3%) undergoing complex segmentectomy in the Routine group had inadequate resection margins and required resection of additional lung tissue.ConclusionRoutine segmentectomy can significantly shorten the operation time and might prevent postoperative air leakage in uniportal segmentectomy for lung GGOs. However, precision segmentectomy may be more precise for complex cases, ensuring adequate resection margins and lymph node dissection.

Background and objectives: In patients with metastatic renal cell cancer (mRCC), cytoreductive nephrectomy (CN) may occasionally be performed. However, the role of lymph node dissection (LND) for such cases is unknown in era of target therapy. To test the effect of LND at CN on cancer-specific survival (CSS), overall survival (OS) in era of target therapy compared with no LND in patients with mRCC. Methods: A total of 4690 mRCC patients treated with CN were identified within the Surveillance, Epidemiology, and End Result (SEER) database (2006-2015). Survival differences were assessed by Kaplan-Meier estimate and compared using log-rank test. Multivariable Cox regression analysis (MCR) was used to evaluate the effect of LND on CSS and OS. Results: Within the SEER database, 1902 (40.6%) of 4690 mRCC patients underwent LND at CN. MCR analysis showed that LND at CN exhibited lower CSS (hazard ratio [HR] 1.18, 95% confidence interval (CI) 1.09-1.27; p < 0.01) and OS (HR 1.13, 95% CI 1.05-1.21; p < 0.01) compared with non-LND in mRCC patients. The adverse effect of LND on CSS and OS were also detected in metastatic patients with clear cell RCC (ccRCC) and non-ccRCC (all p

High utility sequential pattern mining (HUSPM) is an emerging topic in data mining. Compared with the previous topics (sequential pattern mining and high utility itemset mining), HUSPM can provide more applicable knowledge, for it comprehensively considers utility indicating the business value and sequential indicating the causality of different items. However, the combination of utility and sequential brings the dramatic challenges and makes HUSPM more difficult than the previous problems. In this paper, we propose an two efficient algorithms, HUS-UT and HUS-Par, for HUSPM. The proposed HUS-UT algorithm adopts a novel data structure named Utility-Table to facilitate the utility calculation, so it can find the desired patterns quickly. The HUS-Par algorithm is a parallel version of HUS-UT based on the thread model, which also exploits two balance strategies to improve efficiency. We also conduct substantially experiments to evaluate the performance of our algorithms. The experimental results show that our algorithms are much faster than the state-of-the-art algorithms.

Acute lung injury (ALI) is characterized by protein-rich pulmonary edema, critical hypoxemia, and influx of pro-inflammatory cytokines and cells. There are currently no effective pharmacon therapies in clinical practice. Syndecan-1 in endothelial cells has potential to protect barrier function of endothelium and suppress inflammation response. Thus, the present study was to identify whether exosomes with encapsulation of syndecan-1 could achieve ideal therapeutic effects in ALI. Exosomes were isolated from the conditional medium of lentivirus-transfected mouse pulmonary microvascular endothelial cells (MPMVECs) and characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and western blotting. ALI mouse models were induced via intratracheal administration of lipopolysaccharide (LPS) and treated with exosomes. Lung edema, inflammation, and glycocalyx thickness were examined. The possible mechanism was verified by immunoblotting in MPMVECs. The purified exosomes included SDC1-high-Exos and SDC1-low-Exos which loaded with up-regulated syndecan-1 and down-regulated syndecan-1 respectively. Compared with SDC1-low-Exos, administration of SDC1-high-Exos could ameliorate lung edema and inflammation, attenuate number of cells and protein levels in bronchoalveolar lavage fluid (BALF), and preserve glycocalyx. Furthermore, SDC1-high-Exos also mitigated the expression of pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6 following LPS challenge. In MPMVECs, SDC1-high-Exos decreased stress fiber formation and ameliorated monolayer hyper-permeability after LPS stimulation. Western blotting analysis demonstrated that FAK/p190RhoGAP/RhoA/ROCK/NF-κB signaling pathway may be involved in LPS-induced ALI. In conclusion, SDC1-high-Exos play a pivotal role in ameliorating LPS-stimulated ALI models and may be served as a potential therapeutic agent for clinical application in the future.

Fluconazole for fungal infections and amiodarone for arrhythmia are commonly prescribed medications, and coadministration of such medications is sometimes inevitable in clinical practice. However, both medications have been associated with prolonged QTc intervals and subsequent arrhythmias, which are sometimes fatal. We present the case of a 75-year-old man with sudden cardiac arrest triggered by coadministration of fluconazole and amiodarone, which raises the need for caution regarding coadministration of these medications. To our knowledge, this case has not been previously described.

MicroRNAs (miRNAs) are small noncoding RNAs that have a pivotal role in the post-transcriptional regulation of gene expression by sequence-specifically targeting multiple mRNAs. Although miR-33a was recently reported to play an important role in lipid homeostasis, atherosclerosis, and hepatic fibrosis, the functions of miR-33a in tumor progression and metastasis are largely unknown. Here, we found that downregulated miR-33a in breast cancer tissues correlates with lymph node metastasis. MiR-33a expression is significantly lower in the highly metastatic breast cancer cell lines than the noncancerous breast epithelial cells and non-metastatic breast cancer cells. Moreover, the overexpression of miR-33a in metastatic breast cancer cells remarkably decreases cell proliferation and invasion in vitro and significantly inhibits tumor growth and lung metastasis in vivo, whereas its knockdown in non-metastatic breast cancer cells significantly enhances cell proliferation and invasion in vitro and promotes tumor growth and lung metastasis in vivo. Combining bioinformatics prediction and biochemical analyses, we showed that ADAM9 and ROS1 are direct downstream targets of miR-33a. These findings identified miR-33a as a negative regulator of breast cancer cell proliferation and metastasis.

Image quality assessment (IQA) of an image is a vital research direction in the field of image processing. With the quickly developing evaluation methods, study of image quality evaluation method has a profound impact on image and video processing. At present, most of the image quality assessment methods are based on full reference. The traditional quality evaluation method based on structural similarity has the characteristics of narrow application range, unstable evaluation algorithm and so on. The difficulties of obtaining the original image and the difficulty of the reference model design directly incented the development of the semi reference IQA. In this context, a topic-based image quality evaluation process grounded on local information and structure information is proposed. Compared to the traditional image quality evaluation algorithm, the structure similarity has been improved by combining local information. The results show that the evaluation results of the method are more reasonable and stable, which provides a good reference for the post processing of the image.

In the version of this article originally published, a sentence was erroneously included in the author contributions, and information regarding second shared authorship was missing from the author contributions. The following should not have been included in the author contributions: "C.W. and A.J.R.H. supervised the work presented in Figs. 1, 2, 5, 6; P.Z. and C.S. supervised the work presented in Figs. 3, 4." Additionally, this sentence should have appeared at the beginning of the author contributions: "These authors contributed equally: C.W., P.F.Z., C.S., and A.J.R.H." The errors have been corrected in the print, PDF and HTML versions of the article.

The abnormal expression of the chicken ovalbumin upstream promoter transcription factor 2 (COUP‑TFII) is associated with numerous forms of cancer, including gastric, prostate, colon and lung cancer. However, previous studies investigating the association between COUP‑TFII expression and the occurrence, recurrence, invasion and metastasis of gastric cancer are limited in number. In the present study, it was revealed that the expression of COUP‑TFII is significantly reduced in gastric carcinoma tissues compared with normal gastric mucosa cells (GES‑1). In addition, the expression of COUP‑TFII was also reduced in gastric cancer cell lines compared with GES‑1 cells. Furthermore, it was revealed that ectopic expression of COUP‑TFII was able to suppress the proliferation, migration and invasion of gastric cells, as well as inhibit hepatic metastasis, in vivo. In addition, it was demonstrated that COUP‑TFII knockdown was able to promote the proliferation, migration and invasion of GES‑1 cells in vitro. Furthermore, database analysis suggested that COUP‑TFII expression in patients with gastric cancer is correlated with clinical stage classification and increased expression levels of COUP‑TFII improved overall survival rates in patients with gastric cancer. The results of the present study suggest that COUP‑TFII functions as a significant regulatory suppressor of gastric cancer growth and metastasis, and suggests that COUP‑TFII may serve as a novel diagnostic and prognostic biomarker for gastric cancer metastasis.

miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasion while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy.

MicroRNAs are a class of small noncoding RNAs that regulate gene expression post-transcriptionally either by inhibiting protein translation or by causing the degradation of target mRNAs. Current evidence indicates that miR-33b is involved in the regulation of lipid metabolism, cholesterol homeostasis, glucose metabolism and several human diseases; however, whether miR-33b contributes to the pathogenesis of human cancers and participates in the regulation of self-renewal of human cancer stem cells remains unknown. Here, we report the identification of miR-33b as a negative regulator of cell stemness and metastasis in breast cancer. Compared with paired normal breast tissues, miR-33b expression is downregulated in breast tumor samples and is inversely correlated with lymph node metastatic status. Ectopic overexpression of miR-33b in highly metastatic breast cancer cells suppresses cell self-renewal, migration and invasion in vitro and inhibits lung metastasis in vivo. Conversely, miR-33b knockdown promotes the self-renewal, migration and invasion capabilities of noncancerous mammary epithelial cells. The mechanism through which miR-33b inhibits the stemness, migration and invasion of breast cancer cells is by targeting HMGA2, SALL4 and Twist1. These data indicate that miR-33b acts as an onco-suppressive microRNA in breast cancer progression by inhibiting the stemness and metastasis of breast cancer cells.

Brillouin distributed optical fiber sensing system based on spontaneous Brillouin scattering frequency shift measurement may measure temperature in the optical fiber, due to the dependence of spontaneous Brillouin scattering frequency shift on temperature. In this paper, nonlinear theoretical models of the Brillouin spectrum in the BOTDR temperature sensing system are analyzed. The model parameters are optimized with Levenberg-Marquardt algorithm. By numerical calculation, it is indicated that pseudo-Voigt function can approach approximated the Voigt profile well and quickly.

Apolipoprotein-E (ApoE) has been implicated in Alzheimer’s disease, atherosclerosis, and other unresolvable inflammatory conditions but a common mechanism of action remains elusive. We found in ApoE-deficient mice that oxidized lipids activated the classical complement cascade (CCC), resulting in leukocyte infiltration of the choroid plexus (ChP). All human ApoE isoforms attenuated CCC activity via high-affinity binding to the activated CCC-initiating C1q protein (KD~140–580 pM) in vitro, and C1q–ApoE complexes emerged as markers for ongoing complement activity of diseased ChPs, Aβ plaques, and atherosclerosis in vivo. C1q–ApoE complexes in human ChPs, Aβ plaques, and arteries correlated with cognitive decline and atherosclerosis, respectively. Treatment with small interfering RNA (siRNA) against C5, which is formed by all complement pathways, attenuated murine ChP inflammation, Aβ-associated microglia accumulation, and atherosclerosis. Thus, ApoE is a direct checkpoint inhibitor of unresolvable inflammation, and reducing C5 attenuates disease burden. ApoE is a direct checkpoint inhibitor of unresolvable inflammation in neurodegenerative and cardiovascular diseases