Incorporating MicroRNA into molecular phenotypes of circulating tumor cells enhances the prognostic accuracy for patients with metastatic breast cancer

Background. The molecular phenotype of circulating tumor cells (CTCs) was associated with clinical outcome of patients with breast cancer. CTCs isolated from patients with metastatic breast cancer (MBC) display a unique microRNA (miRNA) expression profile. The aim of this study was to enhance the prognostic accuracy of the CTC phenotype in patients with MBC, by incorporating miRNA into a combined prediction model. Subjects, Materials, and Methods. CTCs were detected by CellSearch and enriched by magnetic cell sorting. miRNA deep sequencing and quantitative polymerase chain reaction were used to screen and verify potentially CTC‐specific miRNA candidates. Patients with MBC were enrolled from two independent cohorts, and overall survival (OS) and chemotherapy response were analyzed. Results. We screened and identified that miR‐106b was an upregulated molecule in patients with MBC with CTC ≥5/7.5 mL (n = 16) compared with patients with CTC = 0/7.5 mL (n = 16) and healthy donors (n = 8). The expression of CTC‐specific miR‐106b correlated with vimentin and E‐cadherin in CTC and acted as an independent factor for predicting OS (hazard ratio 2.157, 95% confidence interval [CI] 1.098–4.239, p = .026). Although CTC‐specific miR‐106b, E‐cadherin, and vimentin showed a prognostic potential independently, the prognostic performance for OS based on the combination of three markers was significantly enhanced in Cohort 1 (area under the curve [AUC] 0.752, 95% CI 0.658–0.847, n = 128) and further validated in Cohort 2 (AUC 0.726, 95% CI 0.595–0.856, n = 91). Besides, a combined model incorporating miR‐106b was associated with therapy response. Conclusion. The phenotypic assemblies of CTC incorporating miR‐106b show enhanced prognostic accuracy of overall survival in patients with MBC

The C4 Protein of TbLCYnV Promotes SnRK1 β2 Degradation Via the Autophagy Pathway to Enhance Viral Infection in <i>N. benthamiana</i>

Geminiviruses are a group of single-stranded DNA viruses that have developed multiple strategies to overcome host defenses and establish viral infections. Sucrose nonfermenting-1-related kinase 1 (SnRK1) is a key regulator of energy balance in plants and plays an important role in plant development and immune defenses. As a heterotrimeric complex, SnRK1 is composed of a catalytic subunit α (SnRK1 α) and two regulatory subunits, β and γ. Previous studies on SnRK1 in plant defenses against microbial pathogens have mainly focused on SnRK1 α. In this study, we validated the interaction between the C4 protein encoded by tobacco leaf curl Yunnan virus (TbLCYnV) and the regulatory subunit β of Nicotiana benthamiana SnRK1, i.e., NbSnRK1 β2, and identified that the Asp22 of C4 is critical for TbLCYnV C4–NbSnRK1 β2 interactions. NbSnRK1 β2 silencing in N. benthamiana enhances susceptibility to TbLCYnV infection. Plants infected with viral mutant TbLCYnV (C4D22A), which contains the mutant version C4 (D22A) that is incapable of interacting with NbSnRK1 β2, display milder symptoms and lower viral accumulation. Furthermore, we discovered that C4 promotes NbSnRK1 β2 degradation via the autophagy pathway. We herein propose a model by which the geminivirus C4 protein causes NbSnRK1 β2 degradation via the TbLCYnV C4–NbSnRK1 β2 interaction to antagonize host antiviral defenses and facilitates viral infection and symptom development in N. benthamiana

The first experiment to transmit RF data in OAM mode with optical-assisted circular antenna array

We conducted the first experiment to transmit an RF IQ signal in OAM mode by OCAA, to prove that OAM modes coexists with IQ modulation and could be measured. Directionality and transmission quality is assessed

A flame retardant containing dicyandiamide and aluminum hypophosphite for polyethylene

Polyethylene (PE) is a widely used industrial plastic, but its flammable feature limits its further application. A novel composite based on dicyandiamide (DICY) and aluminum hypophosphite (AHP) was integrated into PE. FT-IR confirmed the chemical structures of the composite. During vertical burning and limiting oxygen index tests, the UL-94 flame retardant grade reached level V-0 and the LOI index increased from 18.8 % to 26.3 % when the ratio of AHP and DICY was 4: 1 (occupying 20 wt% of PE). The CCT tests showed the peak heat release rate of 4-AHP/DICY (AHP: DICY = 4: 1) decreased from 620.3 to 323.4 kW/m2 compared with pure PE. Moreover, the carbon residue of 4-AHP/DICY was higher than that of other samples. After cone calorimetry tests, a compact and stable carbon layer formed on the surface of PE composites through the digital photographs and SEM images of the char residue

Chemotherapy-induced microbiota exacerbates the toxicity of chemotherapy through the suppression of interleukin-10 from macrophages

ABSTRACTThe gut microbiota has been shown to influence the efficacy and toxicity of chemotherapy, thereby affecting treatment outcomes. Understanding the mechanism by which microbiota affects chemotherapeutic toxicity would have a profound impact on cancer management. In this study, we report that fecal microbiota transplantation from oxaliplatin-exposed mice promotes toxicity in recipient mice. Splenic RNA sequencing and macrophage depletion experiment showed that the microbiota-induced toxicity of oxaliplatin in mice was dependent on macrophages. Furthermore, oxaliplatin-mediated toxicity was exacerbated in Il10-/- mice, but not attenuated in Rag1-/- mice. Adoptive transfer of macrophage into Il10-/- mice confirmed the role of macrophage-derived IL-10 in the improvement of oxaliplatin-induced toxicity. Depletion of fecal Lactobacillus and Bifidobacterium was associated with the exacerbation of oxaliplatin-mediated toxicity, whereas supplementation with these probiotics alleviated chemotherapy-induced toxicity. Importantly, IL-10 administration and probiotics supplementation did not attenuate the antitumor efficacy of chemotherapy. Clinically, patients with colorectal cancer exposed to oxaliplatin exhibited downregulation of peripheral CD45+IL-10+ cells. Collectively, our findings indicate that microbiota-mediated IL-10 production influences tolerance to chemotherapy, and thus represents a potential clinical target

Integrating Anti-Influenza Virus Activity and Chemical Pattern Recognition to Explore the Quality Evaluation Method of Lonicerae Japonicae Flos

Lonicerae japonicae flos (LJF, Lonicera japonica Thunb.) is adopted as a core herb for preventing and treating influenza. However, the anti-influenza virus components of LJF and the impact of quality-affecting factors on the anti-influenza activity of LJF have not been systematically investigated. In this study, a strategy integrating anti-influenza virus activity, ultrahigh-performance liquid chromatography fingerprint and chemical pattern recognition was proposed for the efficacy and quality evaluation of LJF. As a result, six bioactive compounds were screened out and identified as neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, 4,5-Di-O-caffeoylquinic acid, sweroside and secoxyloganin. Based on the bioactive compounds, chemical pattern recognition models of LJF were established by a linear discriminant analysis (LDA). The results of the LDA models and anti-influenza virus activity demonstrated that cultivation pattern significantly affected the anti-influenza effect of LJF and that the neuraminidase inhibition rate of wild LJF was significantly higher than that of cultivated LJF. Moreover, the quality of LJF samples with different processing methods and geographical origins showed no obvious difference. Overall, the proposed strategy in the current study revealed the anti-influenza virus components of LJF and provided a feasible method for thequality evaluation of LJF, which has great importance for assuring the clinical effect against influenza of LJF

MOESM1 of Dual-drug loaded nanoneedles with targeting property for efficient cancer therapy

Additional file 1: Figure S1. Standard curves of MTX in DMF via ultraviolet spectroscopy. Figure S2. Standard curves of HCPT in DMF via fluorescence spectroscopy

Role of lncRNA Has2os in Skeletal Muscle Differentiation and Regeneration

Long non-coding RNAs (lncRNAs) regulate a series of physiological processes and play an important role in development, metabolism and disease. Our previous studies showed that lncRNAs involved in skeletal muscle differentiation. Here, we demonstrated that lncRNA Has2os is highly expressed in skeletal muscle and significantly elevated during skeletal cell differentiation. The knockdown of Has2os inhibited myocyte fusion and impeded the expression of the myogenic factors MyHC and Mef2C. Mechanically, Has2os regulates skeletal muscle differentiation by inhibiting the JNK/MAPK signaling pathway. Furthermore, we also revealed that Has2os is involved in the early stage of regeneration after muscle injury, and the JNK/MAPK signaling pathway is activated at both protein and mRNA levels during early repair. Our results demonstrate the new function of lncRNA Has2os, which plays crucial roles during skeletal muscle differentiation and muscle regeneration, providing a basis for the therapy of lncRNA-related muscle diseases

Risk score = LncRNAs associated with doxorubicin metabolism can be used as molecular markers for immune microenvironment and immunotherapy in non-small cell lung cancer

Doxorubicin is the most effective anthracycline chemotherapy drug in the treatment of cancer, and it is an effective single agent in the treatment of non-small cell lung cancer (NSCLC). There is a lack of studies on the differentially expressed doxorubicin metabolism-related lncRNAs in NSCLC. In this study, we extracted related genes from the TCGA database and matched them with lncRNAs. Doxorubicin metabolism-related lncRNA-based gene signatures (DMLncSig) were gradually screened from univariate regression, LASSO regression, and multivariate regression analysis, and the risk score model was constructed. These DMLncSig were subjected to a GO/KEGG analysis. We then used the risk model to construct the TME model and analyze drug sensitivity. The IMvigor 210 immunotherapy model was cited for validation. Eventually, we performed tumor stemness index differences, survival, and clinical correlation analyses