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.
We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). ...Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.
Surface plasmon resonance microscopy (SPRM) is a versatile platform for chemical and biological sensing and imaging. Great progress in exploring its applications, ranging from single‐molecule sensing ...to single‐cell imaging, has been made. In this Minireview, we introduce the principles and instrumentation of SPRM. We also summarize the broad and exciting applications of SPRM to the analysis of single entities. Finally, we discuss the challenges and limitations associated with SPRM and potential solutions.
Surface plasmon resonance microscopy has emerged as a versatile platform for single‐molecule sensing and single‐cell imaging with high spatiotemporal resolution. This Minireview highlights the recent advances in the SPRM‐based analysis of single entities. Future challenges and their limitations as well as potential research directions are discussed.
The hydrogenation of esters catalyzed by a manganese complex of phosphine‐aminopyridine ligand was developed. Using this protocol, a variety of (hetero)aromatic and aliphatic carboxylates including ...biomass‐derived esters and lactones were hydrogenated to primary alcohols with 63–98% yields. The manganese catalyst was found to be active for the hydrogenation of methyl benzoate, providing benzyl alcohol with turnover numbers (TON) as high as 45,000. Investigation of catalyst intermediates indicated that the amido manganese complex was the active catalyst species for the reaction.
Efficient recruitment and angiogenesis of endothelial progenitor cells (EPCs) are critical during a thrombus event. However, the details of EPC recruitment and the regulation of angiogenesis have not ...been fully determined. The aim of this study was to determine the role of the long noncoding (lnc)RNA Wilms tumor 1 associated protein pseudogene 1 (WTAPP1) in regulation of the migration and angiogenesis of EPCs. EPCs were isolated from human peripheral blood and characterized by flow cytometry, after which lentivirus‐mediated lncRNA WTAPP1 overexpression and knockdown were performed. Scratch assay, Transwell assay, and in vitro and in vivo tube formation assays were performed to measure cell migration, invasion, and angiogenic abilities, respectively. Moreover, a microarray screen, bioinformatic prediction, and quantitative PCR and Western blot of miRNAs interacting with lncRNA WTAPP1 were conducted. Western blot was carried out to elucidate the relationship among WTAPP1, miR‐3120‐5P, and MMP‐1 in the autophagy pathway. WTAPP1 positively regulated migration, invasion, and in vitro and in vivo tube formation in EPCs by increasing MMP‐1 expression and activating PI3K/Akt/mTOR signaling. Furthermore, WTAPP1 contains a putative miR‐3120‐5P binding site. Suppression of WTAPP1 by miR‐3120‐5P decreased the level of MMP‐1. In addition, we demonstrated that suppression of the autophagy pathway is involved in the effects of WTAPP1 on EPC migration and angiogenesis. The lncRNA WTAPP1, a molecular decoy for miR‐3120‐5p, regulates MMP‐1 expression via the PI3K/Akt and autophagy pathways, thereby mediating cell migration and angiogenesis in EPCs. Acting as a potential therapeutic target, the lncRNA WTAPP1 may play an important role in the pathogenesis of DVT. Stem Cells 2018;36:1863–12
The long noncoding RNA Wilms tumor 1 associated protein pseudogene 1, a molecular decoy for miR‐3120‐5p, regulates MMP‐1 expression via the PI3K/Akt and autophagy pathways, thereby mediating cell migration and angiogenesis in endothelial progenitor cells.
The electrochemical oxygen evolution reaction (OER) is a core electrode reaction for the renewable production of high‐purity hydrogen, carbon‐based fuel, synthetic ammonia, etc. However, the sluggish ...kinetics of the OER result in a high overpotential and limit the widespread application of OER‐based technologies. Recent studies have shown that bimetallic‐based materials with the synergism of different metal components to regulate the adsorption and dissociation energy of intermediates are promising OER electrocatalyst candidates with a lower cost and energy consumption. In the past two decades, tremendous efforts have been devoted to developing OER applications of bimetallic‐based materials with a focus on compositions, phase, structure, etc., to highlight the synergism of different metal components. However, there is a lack of critical thinking and organized analysis of OER applications with bimetallic‐based materials. This review critically discusses the challenges of developing bimetallic‐based OER materials, summarizes the current optimization strategies to enhance both activity and stability, and highlights the state‐of‐the‐art electrocatalysts for OER. The relationship between the componential/structural features of bimetallic‐based materials and their electrocatalytic properties is presented to form comprehensive electronic and geometric modifications based on thorough analysis of the reported works and discuss future efforts to realize sustainable bimetallic‐based OER applications.
The impressive progress in the rational design of bimetals and bimetallic compounds toward oxygen evolution reaction (OER) is summarized. Based on the main advantages and challenges for the bimetallic‐based OER electrocatalysts, the optimization strategies are presented to modify the electronic structure and geometric construction to highlight the synergism characteristics, including compositional regulation, elemental doping, coordination adjustment, interfacial structure establishment, morphology control, and support interaction for achieving efficient OER performance.
The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinical ...isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated by using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.
The Nanwenghe Wetlands Reserve in the Yile'huli Mountains is a representative region of the Xing'an permafrost. The response of permafrost to climate change remains unclear due to limited field ...investigations. Thus, longer-term responses of the ground thermal state to climate change since 2011 have been monitored at four sites with varied surface characteristics: Carex tato wetland (P1) and shrub-C. tato wetland (P2) with a multi-year average temperatures at the depth of zero annual amplitude (TZAA) of −0.52 and −1.19 °C, respectively; Betula platyphylla-Larix gmelinii (Rupr.) Kuzen mixed forest (P3) with TZAA of 0.17 °C, and; the forest of L. gmelinii (Rupr.) Kuzen (P4) with TZAA of 1.65 °C. Continuous observations demonstrate that the ecosystem-protected Xing'an permafrost experienced a cooling under a warming climate. The temperature at the top of permafrost (TTOP) rose (1.8 °C per decade) but the TZAA declined (−0.14 °C per decade), while the active layer thickness (ALT) thinned from 0.9 m in 2012 to 0.8 m in 2014 at P1. Both the TTOP and TZAA increased (0.89 and 0.06 °C per decade, respectively), but the ALT thinned from 1.4 m in 2012 to 0.7 m in 2016 at P2. Vertically detached permafrost at P3 disappeared in summer 2012, with warming rates of +0.42 and + 0.17 °C per decade for TTOP and TZAA, respectively. However, up to date, the ground thermal state has remained stable at P4. We conclude that the thermal offset is crucial for the preservation and persistence of the Xing'an permafrost at the southern fringe.
A Ni‐catalyzed hydroarylation of styrenes and 1,3‐dienes with organoboron compounds has been developed. The reaction offers a highly selective approach to diarylalkanes and allylarenes under ...redox‐neutral conditions. In this hydroarylation reaction, a new strategy that uses the proton of methanol to generate the active catalyst species Ni−H was developed. The Ni‐catalyzed hydroarylation, combined with a Ir‐catalyzed C−H borylation, affords a very efficient and straightforward access to a retinoic acid receptor agonist.
OH yeah: A nickel(0)‐catalyzed hydroarylation of alkenes with organoboron reagents using an alcohol OH group as the H‐atom source is reported. The reaction offers a highly selective approach to diarylalkanes and allylarenes under redox‐neutral conditions.
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