In the upcoming decades, connected vehicles will join regular vehicles to appear on roads, and the characteristics of traffic flow will be changed accordingly. To model the heterogeneous traffic ...mixing regular and connected vehicles, a generic car-following framework is first proposed in this paper. A linear stability condition is theoretically derived, which indicates that the stability of the heterogeneous traffic is closely related to the penetration rate and the spatial distribution of connected vehicles. The generic car-following framework is applied by taking the Intelligent Driver Model as an example, and it is shown that connected vehicles can obviously enhance the stability of traffic flow and improve traffic efficiency in particular when traffic is in congestion. Moreover, a driver assistance strategy based on distributed feedback control is developed for connected vehicles, and the simulation results show that the proposed driver assistance strategy performs satisfactorily in stabilizing traffic as well as improving traffic efficiency.
Background
Molecular subtyping of triple‐negative breast cancers (TNBCs) via gene expression profiling is essential for understanding the molecular essence of this heterogeneous disease and for ...guiding individualized treatment. We aim to devise a clinically practical method based on immunohistochemistry (IHC) for the molecular subtyping of TNBCs.
Materials and Methods
By analyzing the RNA sequencing data on TNBCs from Fudan University Shanghai Cancer Center (FUSCC) (n = 360) and The Cancer Genome Atlas data set (n = 158), we determined markers that can identify specific molecular subtypes. We performed immunohistochemical staining on tumor sections of 210 TNBCs from FUSCC, established an IHC‐based classifier, and applied it to another two cohorts (n = 183 and 214).
Results
We selected androgen receptor (AR), CD8, FOXC1, and DCLK1 as immunohistochemical markers and classified TNBCs into five subtypes based on the staining results: (a) IHC‐based luminal androgen receptor (IHC‐LAR; AR‐positive +), (b) IHC‐based immunomodulatory (IHC‐IM; AR‐negative −, CD8+), (c) IHC‐based basal‐like immune‐suppressed (IHC‐BLIS; AR−, CD8−, FOXC1+), (d) IHC‐based mesenchymal (IHC‐MES; AR−, CD8−, FOXC1−, DCLK1+), and (e) IHC‐based unclassifiable (AR−, CD8−, FOXC1−, DCLK1−). The κ statistic indicated substantial agreement between the IHC‐based classification and mRNA‐based classification. Multivariate survival analysis suggested that our IHC‐based classification was an independent prognostic factor for relapse‐free survival. Transcriptomic data and pathological observations implied potential treatment strategies for different subtypes. The IHC‐LAR subtype showed relative activation of HER2 pathway. The IHC‐IM subtype tended to exhibit an immune‐inflamed phenotype characterized by the infiltration of CD8+ T cells into tumor parenchyma. The IHC‐BLIS subtype showed high expression of a VEGF signature. The IHC‐MES subtype displayed activation of JAK/STAT3 signaling pathway.
Conclusion
We developed an IHC‐based approach to classify TNBCs into molecular subtypes. This IHC‐based classification can provide additional information for prognostic evaluation. It allows for subgrouping of TNBC patients in clinical trials and evaluating the efficacy of targeted therapies within certain subtypes.
Implications for Practice
An immunohistochemistry (IHC)‐based classification approach was developed for triple‐negative breast cancer (TNBC), which exhibited substantial agreement with the mRNA expression‐based classification. This IHC‐based classification (a) allows for subgrouping of TNBC patients in large clinical trials and evaluating the efficacy of targeted therapies within certain subtypes, (b) will contribute to the practical application of subtype‐specific treatment for patients with TNBC, and (c) can provide additional information beyond traditional prognostic factors in relapse prediction.
This article describes an immunohistochemistry‐based approach to classification of triple‐negative breast cancers into molecular subtypes for purposes of the translation of TNBC molecular classification into clinical practice.
Rational utilization of the rich light‐bio‐matter interplay taking place in single‐cell analysis represents a new technological direction in the field. The light‐fueled operation is expected to ...achieve advanced photoelectrochemical (PEC) single‐cell analysis with unknown possibilities. Here, a PEC nanoreactor capable of single‐cell sampling and near zero‐background Faradaic detection of intracellular microRNA (miR) is devised by the construction of a small reaction chamber accommodating the target‐triggered hybridization chain reaction for binding the metallointercalator of Ru(bpy)2(dppz)2+ as the signal reporter. Light stimulation of the dsDNA/metallointercalator adduct will induce the generation of photocurrents, underpinning a zero‐biased and near zero‐background PEC method toward Faradaic detection of non‐electrogenic miR at the single‐cell level. Using this nanotool, lower miR concentration in the near‐nucleus region than that in the main cytosol was revealed.
A photoelectrochemical nanoreactor was devised for single‐cell sampling and near zero‐background faradic detection of intracellular microRNA. This platform provided a new perspective for exploring light‐biomatter interplay toward single‐cell studies.
New tools for single‐cell interrogation enable deeper understanding of cellular heterogeneity and associated cellular behaviors and functions. Information of RNA expression in single cell could ...contribute to our knowledge of the genetic regulatory circuits and molecular mechanism of disease development. Although significant progresses have been made for intracellular RNA analysis, existing methods have a trade‐off between operational complexity and practical feasibility. We address this challenge by combining the ionic current rectification property of nanopipette reactor with duplex‐specific nuclease‐assisted hybridization chain reaction for signal amplification to realize a simple and practical intracellular nanosensor with minimal invasiveness, which enables single‐cell collection and electrochemical detection of intracellular RNA with cell‐context preservation. Systematic studies on differentiation of oncogenic miR‐10b expression levels in non‐malignant breast cells, metastatic breast cancer cells as well as non‐metastatic breast cancer cells were then realized by this nanotool accompanied by assessment of different drugs effects. This work has unveiled the ability of electrochemistry to probe intracellular RNA and opened new opportunities to study the gene expression and heterogeneous complexity under physiological conditions down to single‐cell level.
A DSN‐assisted ICR‐nanopipette was fabricated for tracking the drug‐induced variation of the oncogenic miR‐10b expression levels of a dynamic manner. This method unveils the ability of electrochemistry to probe intracellular RNA and to study the gene expression and heterogeneous complexity under physiological conditions down to single‐cell level.
Perovskite (PVSK) photovoltaics have been a promising field in the exploitation of renewable energy due to the fascinating performances of PVSK materials and devices. Although the efficiency is ...gradually approaching that of traditional solar cells, the stability is still a challenge. Hence, tomato lycopene, a botanic antioxidant, is introduced as a modification layer on the PVSK absorber layer to prevent moisture and oxygen erosion, for enhanced both intrinsic and environmental stabilities. This inserted protection layer can also interact with the PVSK material through carbon‐halogen bonds and influence its crystallinity. Therefore, PVSK films are obtained with less defects and better intrinsic stability. The device achieved a champion outdoor efficiency at AM 1.5G more than 21% and its indoor efficiency at 1000 lux can reach 40.24%. In addition, the efficiency can keep almost 90% of the original value after exposure to wet oxygen ambience for 1000 h. The antioxidant gives a unique perspective towards enhancing the stability of solar cells
Lycopene, a botanic antioxidant, is introduced to modify the perovskite film for adjusting crystallization through carbon‐halogen bonds, and preventing moisture and oxygen erosion. Therefore, the optimized device yields efficiencies of 21.04% under 100 mW cm−2 and 40.24% at 1000 lux. It also retains almost 90% of the original efficiency value after exposure to wet oxygen ambience for 1000 h.
An efficient asymmetric dearomative 3+2 cycloaddition reaction of 2‐nitroindoles and 2‐nitrobenzothiophenes with 3‐isothiocyanato oxindoles was developed by using a chiral Zn(OTf)2/bis(oxazoline) ...complex as a catalyst. With the developed protocol, a range of enantioenriched complex heterocyclic compounds containing three contiguous stereocenters, one of which is spirocyclic center, could be obtained in quantitative yields with excellent diastereo‐ and enantioselectivities. The potential utility of this method was showcased by the diverse transformations of the products.
Background
One of the most striking characteristics of nasopharyngeal carcinoma (NPC) is the presence of a very abundant immune cells infiltrate containing mainly T‐lymphocytes. The purpose of this ...study was to present our analysis providing a comprehensive characterization of antitumor inflammatory response in NPC.
Methods
The densities of 9 types of inflammatory cells were assessed in 197 patients with NPC, including CD3 + T‐lymphocytes, CD8 + cytotoxic T‐lymphocytes, CD20 + B‐lymphocytes, CD56 + natural killer (NK) cells, FOXP3 + regulatory T‐lymphocytes, CD1a + immature dendritic cells, CD83 + mature dendritic cells, neutrophil elastase + neutrophils, and tryptase + mast cells. We characterized the inflammatory infiltrate in relation to clinical stage and patient survival. The expression of programmed death‐1 (PD‐1) on tumor‐infiltrating lymphocytes (TILs) was also detected. The correlations between PD‐1 expression and clinical characteristics and posttreatment outcome were analyzed.
Results
The patients with NPC with a low density of tumor‐infiltrating FOXP3+, CD8 + T‐lymphocytes, neutrophils, and mast cells showed a significantly longer overall survival (OS) and progression‐free survival (PFS). However, patients with a high density of NK cells showed a better OS and PFS. The densities of NK cells and mast cells could be served as biomarkers for predicting recurrence or distant metastasis in patients with NPC. Moreover, PD‐1 positivity predicted poor prognosis in patients with NPC.
Conclusion
The densities of inflammatory cells are correlated with the prognosis of patients with NPC.
Background and purpose
Motoric cognitive risk syndrome (MCR) is characterized by slow walking speed and subjective memory complaints (SMCs). This study investigated the prevalence and potential risk ...factors of MCR and its association with falls in Chinese community‐dwelling older adults.
Methods
The analysis was based on data from the Rugao Longevity and Aging Study (RuLAS). MCR was defined as the presence of both SMCs and slow walking speed in participants free of major neurocognitive disorders. SMCs were determined according to a positive answer to the question ‘Do you feel you have more problems with memory than most?’ in the 15‐item Geriatric Depression Scale. Slow walking speed was defined as one standard deviation or more below the mean value for patients’ age and sex. Data on falls were derived from a standardized questionnaire.
Results
The prevalence of SMCs, slow walking speed and MCR in the RuLAS cohort (N = 1592) was 51.9%, 15.6% and 8.3%, respectively. After adjusting for other covariates, an occupation of farming (odds ratio OR 2.358, 95% confidence interval CI 1.007–5.521, p = 0.048), history of cerebrovascular disease (OR 2.215, 95% CI 1.032–4.752, p = 0.041) and hospitalization (OR 2.008, 95% CI 1.120–3.602, p = 0.019) were risk factors for MCR. Binary logistic regression analysis indicated that the risk of falls was increased by MCR (OR 1.547, 95% CI 1.009–2.371), SMC (OR 1.308, 95% CI 1.003–1.707) and slow walking speed (OR 1.442, 95% CI 1.030–2.017).
Conclusions
Early identification of potential risk factors of MCR can prevent the occurrence of adverse health events such as falls in the elderly.
Emerging evidence suggests that epithelial‐mesenchymal transitions (EMTs) play important roles in tumor metastasis and recurrence. Understanding molecular mechanisms that regulate the EMT process is ...crucial for improving treatment of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) play important roles in HCC; however, the mechanisms by which miRNAs target the EMT and their therapeutic potential remains largely unknown. To better explore the roles of miRNAs in the EMT process, we established an EMT model in HCC cells by transforming growth factor beta 1 treatment and found that several tumor‐related miRNAs were significantly decreased. Among these miRNAs, miR‐125b expression was most strongly suppressed. We also found down‐regulation of miR‐125b in most HCC cells and clinical specimens, which correlated with cellular differentiation in HCC patients. We then demonstrated that miR‐125b overexpression attenuated EMT phenotype in HCC cancer cells, whereas knockdown of miR‐125b promoted the EMT phenotype in vitro and in vivo. Moreover, we found that miR‐125b attenuated EMT‐associated traits, including chemoresistance, migration, and stemness in HCC cells, and negatively correlated with EMT and cancer stem cell (CSC) marker expressions in HCC specimens. miR‐125b overexpression could inhibit CSC generation and decrease tumor incidence in the mouse xenograft model. Mechanistically, our data revealed that miR‐125b suppressed EMT and EMT‐associated traits of HCC cells by targeting small mothers against decapentaplegic (SMAD)2 and 4. Most important, the therapeutic delivery of synthetic miR‐125b mimics decreased the target molecule of CSC and inhibited metastasis in the mice model. These findings suggest a potential therapeutic treatment of miR‐125b for liver cancer. Conclusion: miR‐125b exerts inhibitory effects on EMT and EMT‐associated traits in HCC by SMAD2 and 4. Ectopic expression of miR‐125b provides a promising strategy to treat HCC. (Hepatology 2015;62:801–815)
Single‐cell epigenetics is envisioned to decipher manifold epigenetic phenomena and to contribute to our accurate knowledge about basic epigenetic mechanisms. Engineered nanopipette technology has ...gained momentum in single‐cell studies; however, solutions to epigenetic questions remain unachieved. This study addresses the challenge by exploring N6‐methyladenine (m6A)‐bearing deoxyribozyme (DNAzyme) confined within a nanopipette for profiling a representative m6A‐modifying enzyme, fat mass and obesity‐associated protein (FTO). Electroosmotic intracellular extraction of FTO could remove the m6A and cause DNAzyme cleavage, leading to the altered ionic current signal. Because the cleavage can release a DNA sequence, we simultaneously program it as an antisense strand against FTO‐mRNA, intracellular injection of which has been shown to induce early stage apoptosis. This nanotool thus features the dual functions of studying single‐cell epigenetics and programmable gene regulation.
An integrated iontronic nanotool was developed for the study of single‐cell epigenetics and programmable gene regulation. With the nanotool, an N6‐methyladenine (m6A)‐modified deoxyribozyme (DNAzyme) was used for profiling a representative m6 A‐modifying enzyme, fat mass and obesity‐associated protein (FTO), which also released a DNA sequence that could be programmed as an antisense strand against intracellular FTO‐mRNA.
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