Alternative splicing (AS) and its regulation play critical roles in cancer, yet the dysregulation of AS and its molecular bases in breast cancer development have not yet been elucidated. Using an
...CRISPR screen targeting RNA-binding proteins, we identified PHD finger protein 5A (PHF5A) as a key splicing factor involved in tumor progression. PHF5A expression was frequently upregulated in breast cancer and correlated with poor survival, and knockdown of PHF5A significantly suppressed cell proliferation, migration, and tumor formation. PHF5A was required for SF3b spliceosome stability and linked the complex to histones, and the PHF5A-SF3b complex modulated AS changes in apoptotic signaling. In addition, expression of a short truncated FAS-activated serine/threonine kinase (FASTK) protein was increased after PHF5A ablation and facilitated Fas-mediated apoptosis. This PHF5A-modulated FASTK-AS axis was widely present in breast cancer specimens, particularly those of the triple-negative subtype. Taken together, our findings reveal that PHF5A serves as an epigenetic suppressor of apoptosis and thus provides a mechanistic basis for breast cancer progression and may be a valuable therapeutic target.
This study provides an epigenetic mechanistic basis for the aggressive biology of breast cancer and identifies a translatable therapeutic target.
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The activities and gene expression of antioxidative enzymes and the ROS content were analyzed in two typical storage-tolerant cultivars (Xushu 32 and Shangshu 19) and another two storage-sensitive ...cultivars (Yanshu 25 and Sushu 16) to explore the association between the storage capacity of sweetpotato (Ipomoea batatas (L.) Lam) and ROS scavenging capability. The storage roots of the storage-tolerant cultivars maintained higher activities and expression levels of antioxidative enzymes, including ascorbate peroxidase (APX), peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD); lower activity and expression of lipoxygenase (LOX); and lower accumulation of ROS metabolites compared with the storage-sensitive cultivars. The antioxidative capability and ROS parameters of leaves were positively correlated with those of storage roots. Our results provide valuable insight for evaluating the storability of sweetpotato cultivars by analyzing the capabilities of the antioxidative system and the contents of ROS metabolites.
We present a simpler and novel design of a six-band terahertz perfect metamaterial absorber (MA) composed of a metal U-shaped closed-ring resonator, a dielectric spacer, and a metal back plate. The ...numerical simulation results demonstrate that it can perform absorption peaks at six resonant frequencies whose peaks average 97.3%. The physical mechanism of the proposed MA is explained by the multipolar plasmon resonance of the structure, thus making the structure very easy to fabricate. Furthermore, the sensing performance of the absorber is analyzed in terms of the overlayer.
Recent studies have shown that circulating microRNAs might be useful, novel biomarkers for the diagnosis of acute myocardial infarction. The aims of this study were to evaluate the expression of ...cardiac-specific miRNAs (miR-1, -133a, -208b, and -499) in patients with acute myocardial infarction and to compare the diagnostic values of these miRNAs with that of cardiac troponin T.
Sixty-seven plasma samples obtained from patients with acute myocardial infarction and 32 plasma specimens collected from healthy volunteers were analyzed in this study. The levels of cardiac-specific miRNAs (miR-1, -133a, -208b, and -499) were measured by quantitative reverse transcription-polymerase chain reaction, and the concentrations of plasma cardiac troponin T were measured using electrochemiluminescence-based methods and an Elecsys 2010 Immunoassay Analyzer.
The levels of plasma miR-1, -133a, -208b, and -499 were significantly higher in acute myocardial infarction patients (all p<0.001) than in healthy volunteers. The expression of the cardiac-specific miRNAs in acute myocardial infarction patients decreased to close to the baseline levels at the time of hospital discharge (all p>0.05). There were no correlations between the levels of the four circulating miRNAs and the clinical characteristics of the study population (all p>0.05). Furthermore, receiver operating characteristic curve analyses showed that the four plasma miRNAs were not superior to cardiac troponin T for the diagnosis of acute myocardial infarction (all p>0.05).
Our results demonstrate that circulating miR-1, -133a, -208b, and -499 may be useful biomarkers in acute myocardial infarction patients but that these miRNAs are not superior to cardiac troponin T for the diagnosis of acute myocardial infarction.
Ferroelectricity in two-dimensional (2D) systems generally arises from phonons and has been widely investigated. On the contrary, electronic ferroelectricity in 2D systems has been rarely studied. ...Using first-principles calculations, the ferroelectric behavior of the buckled blue SiSe monolayer under strain are explored. It is found that the direction of the out-of-plane ferroelectric polarization can be reversed by applying an in-plane strain. And such polarization switching is realized without undergoing geometric inversion. Besides, the strain-triggered polarization reversal emerges in both biaxial and uniaxial strain cases, indicating it is an intrinsic feature of such a system. Further analysis shows that the polarization switching is the result of the reversal of the magnitudes of the positive and negative charge center vectors. And the variation of buckling is found to play an important role, which results in the switch. Moreover, a non-monotonic variation of band gap with strain is revealed. Our findings throws light on the investigation of novel electronic ferroelectric systems.
Unlike conventional ferroelectrics, ferroelectric polarization reversal is realized by strain without undergoing geometric inversion in the blue phase.
Combining ultrasmall NiS2 nanodots with three-dimensional carnation-like CoS2 microstructures is demonstrated to be able to enhance the electrocatalytic activities for both the oxygen and hydrogen ...evolution reactions, leading to efficient overall alkaline water splitting.
•The equilibrium data were well represented by the Freundlich isotherm.•Dominant sludge parameter affecting sorption was protein rather than carbohydrate.•The enhanced sorption of PASs on sludge was ...found when solution pH decreased.•For all PASs, enhanced adsorption occurred with increasing calcium concentration.•Sorption on sludge increases with increasing alkyl chain length for PASs with C5–C15.
Perfluoroalkyl surfactants (PASs) have attracted increasing concerns in recent years due to their global distribution, persistence, bioaccumulation and potential toxicity. Since sludge was a significant source of PASs to environment, the sorption of short (C2–C6) and long-chain (C7–C15) PASs on different sewage sludge was investigated in this study. The equilibrium data were well represented by the Freundlich isotherm and were generally nonlinear. In order to elucidate the sorption mechanism of PASs to sludge, effect of sludge property, solution chemistry and molecular structure were also investigated in details. The dominant sludge parameter influencing sorption of PASs was protein in extracellular polymeric substances. The sorption of PASs onto sludge increased as solution pH decreased. For all the PASs homologues, enhanced adsorption occurred with increasing calcium concentration in solution. For PASs with C5–C15, sorption on sludge increases with increasing alkyl chain length, while for PASs with C2–C5, the association of sludge decreases when the alkyl chain length increases. The perfluorinated sulfonic acid (PFSA) demonstrated substantially stronger sorption than perfluorinated carboxylic acid (PFCA) analog. Evidence for both hydrophobic and electrostatic interactions was found.
An online steady-state load identification method is proposed to solve the problems related to frequency drift, system robustness deterioration, difficulties in controller design due to the ...uncertainties in load and mutual inductance variations of an inductive power transfer (IPT) system. Take a Series-Series-type IPT system as an example, an additional capacitor is added into the system to make the system work in two operating modes, and a mathematical model is established according to the two modes for the system identification. Simulation and experimental results have verified the proposed online load identification method. It has demonstrated that the method is accurate and reliable for identifying uncertain loads and magnetic coupling variations if other system parameters are known. The method can be used to improve the system performance with precise control.
A novel and environmentally friendly lignin-based surfactant sodium lignosulfonate (SLS) modified layered double hydroxide (LDH) flame retardant (LDH-LS) was fabricated via co-precipitation method, ...and subsequently incorporated into polypropylene (PP) matrix to obtain the PP and LDH-LS composites (PP/LDH-LS) by melt blending method. The XRD, FT-IR and XPS results indicated that SLS had successfully modified LDH by adsorbing on the surface of the LDH nanosheet. The WCA and SEM results revealed that the hydrophobic property of LDH-LS had been evidently improved, and it displayed a more homogeneous dispersion than virgin LDH in the PP matrix. Furthermore, cone calorimetry tests (CCT) illustrated that the peak heat release rate (PHRR), total heat release (THR), and total smoke release (TSR) of PP/LDH-LS composites exhibited declines of 62.9%, 25.1%, and 43.3% compared with those of Neat PP, respectively. Besides, the PP/LDH-LS achieved a LOI value of 29.4% and a UL-94 V-0 rating, whereas the PP/LDH showed only a LOI value of 25.2% and a UL-94 V-2 rating at 20 wt% loading. These improvements of flame retardant properties can be attributed to that the well-dispersed LDH-LS and synergistic flame retardancy between LDH and SLS.
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Ulcerative colitis (UC) is an increasingly common condition particularly in developed countries. The lack of satisfactory treatment has fueled the search for alternative therapeutic ...strategies. In recent studies, berberine, a plant alkaloid with a long history of medicinal use in Chinese medicine, has shown beneficial effects against animal models of acute UC. However, UC usually presents as a chronic condition with frequent relapse in patients. How berberine will act on chronic UC remains unclear. In the present study, we adopted dextran sulfate sodium (DSS)-induced chronic relapsing colitis model to assess the ameliorating activity of berberine. Colitis was induced by two cycles of 2.0% DSS for five days followed by 14days of drinking water plus a third cycle consisting of DSS only for five days. The colitis mice were orally administered 20mg/kg berberine from day 13 onward for 30days and monitored daily. The body weight, stool consistency, and stool bleeding were recorded for determination of the disease activity index (DAI). At the end of treatment, animals were sacrificed and samples were collected and subjected to histological, RT-qPCR, Western blot, and LC–MS analyses. Lymphocytes were isolated from spleens and mesenteric lymph nodes (MLN) and cultured for flow cytometry analysis of IL-17 secretion from CD4+ cells and the Th17 cell differentiation. Results showed that berberine significantly ameliorated the DAI, colon shortening, colon tissue injury, and reduction of colonic expression of tight junction (TJ) protein ZO-1 and occludin of colitis mice. Notably, berberine treatment pronouncedly reduced DSS-upregulated Th17-related cytokine (IL-17 and ROR-γt) mRNAs in the colon. Furthermore, the mRNA expression of IL-6 and IL-23, and the phosphorylation of STAT3 in colon tissues from DSS-treated mice were pronouncedly inhibited by berberine. Moreover, the up-regulation of IL-17 secretion from CD4+ cells of spleens and MLNs caused by DSS were significantly reversed by berberine treatment. Furthermore, Th17 cell differentiation from naive CD4+ cells isolated from above DSS colitis mice were suppressed by berberine in a concentration-dependent manner. In summary, we demonstrated for the first time that berberine reduced the severity of chronic relapsing DSS-induced colitis by suppressing Th17 responses. The demonstration of activity in this mouse model supports the possibility of clinical efficacy of berberine in treating chronic UC.
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