•The first meta-analysis on serum copper (Cu) to zinc ratio (Cu/Zn) in breast cancer.•Increased serum Cu and Cu/Zn in breast cancer than that in healthy controls.•Increased serum Cu and Cu/Zn in ...breast cancer than that in benign breast disease.•Decreased serum zinc levels in breast cancer than that in healthy controls.•Decreased serum zinc levels in breast cancer than that in benign breast disease.
More and more studies have investigated the relationship between serum copper (Cu) and/or zinc (Zn) levels and breast cancer (BC). However, the results are inconsistent. It is unclear whether the serum Cu to Zn ratio (Cu/Zn) is associated with BC risk. Therefore, we evaluated serum Cu and Zn concentrations, and Cu/Zn in BC through meta-analysis.
Studies reporting serum Cu and/or Zn concentrations in BC patients and controls from 1991 to 2020 were identified from PubMed, CNKI, and Wanfang databases online. Based on a random effects model, summary standard mean differences (SMDs) and the corresponding 95 % confidence intervals (95 % CIs) were applied to compare the serum levels of Cu, Zn and Cu/Zn between BC patients and controls.
Thirty-six eligible studies involving 5747 female subjects were included. The present study illustrated that the BC patients had significantly higher serum Cu levels than healthy controls (HC) (SMD (95 % CI): 1.99(1.48, 2.49)) and patients with benign breast diseases (BD) (SMD (95 % CI): 0.99(0.38, 1.61)). However, Zn concentrations were statistically decreased in BC patients than HC (SMD (95 % CI): -1.20(-1.74, -0.66)) and BD (SMD (95 % CI): -1.13 (-1.73, -0.54)). Cu/Zn concentrations were remarkably increased in BC patients than HC (SMD (95 % CI): 2.75(1.79, 3.60)) and BD (SMD (95 % CI): 2.98(1.91, 4.05)) in some studies.
The results show that elevated serum levels of Cu and Cu/Zn, as well as decreased Zn might be associated with increased risk of breast cancer. These three parameters have the potential to distinguish breast cancer from benign breast diseases.
Sulfur and polysulfides play important roles on the environment and energy storage systems, especially in the recent hot area of high energy density of lithium–sulfur (Li–S) batteries. However, the ...further development of Li–S battery is still retarded by the lack of complete mechanistic understanding of the sulfur redox process. Herein we introduce a conductive Lewis base matrix which has the ability to enhance the battery performance of Li–S battery, via the understanding of the complicated sulfur redox chemistry on the electrolyte/carbon interface by a combined in operando Raman spectroscopy and density functional theory (DFT) method. The higher polysulfides, Li2S8, is found to be missing during the whole redox route, whereas the charging process of Li–S battery is ended up with the Li2S6. DFT calculations reveal that Li2S8 accepts electrons more readily than S8 and Li2S6 so that it is thermodynamically and kinetically unstable. Meanwhile, the poor adsorption behavior of Li2S n on carbon surface further prevents the oxidization of Li2S n back to S8 upon charging. Periodic DFT calculations show that the N-doped carbon surface can serve as conductive Lewis base “catalyst” matrix to enhance the adsorption energy of Li2S n (n = 4–8). This approach allows the higher Li2S n to be further oxidized into S8, which is also confirmed by in operando Raman spectroscopy. By recovering the missing link of Li2S8 in the whole redox route, a significant improvement of the S utilization and cycle stability even at a high sulfur loading (70%, m/m) in the composite on a simple super P carbon.
A sufficiently large supercurrent can close the energy gap in a superconductor and create gapless quasiparticles through the Doppler shift of quasiparticle energy caused by finite Cooper pair ...momentum. In this gapless superconducting state, zero-energy quasiparticles reside on a segment of the normal-state Fermi surface, whereas the remaining Fermi surface is still gapped. We use quasiparticle interference to image the field-controlled Fermi surface of bismuth telluride (Bi
Te
) thin films under proximity effect from the superconductor niobium diselenide (NbSe
). A small applied in-plane magnetic field induces a screening supercurrent, which leads to finite-momentum pairing on the topological surface states of Bi
Te
. We identify distinct interference patterns that indicate a gapless superconducting state with a segmented Fermi surface. Our results reveal the strong impact of finite Cooper pair momentum on the quasiparticle spectrum.
Regularized Einstein-Gauss-Bonnet theory of gravity in four dimensions is a new attempt to include nontrivial contributions of the Gauss-Bonnet term. In this paper, we make a detailed analysis on ...possible constraints of the model parameters of the theory from recent cosmological observations and some theoretical constraints, as well. Our results show that the theory with vanishing bare cosmological constant, Λ0, is ruled out by the current observational value of wde and the observations of gravitational-wave event GW170817 and the gamma-ray burst (GRB) GRB 170817A, as well. For a nonvanishing bare cosmological constant, instead, our results show that the current observation of the speed of gravitational waves (GWs) measured by GW170817 and GRB 170817A would place a constraint on ˜ α , a dimensionless parameter of the theory, as − 7.78 × 10−16 ≤ ˜ α ≤ 3.33 × 10−15 .
Guangzhou has been the city most affected by the dengue virus (DENV) in China, with a predominance of DENV serotype 1 (DENV‐1). Viral factors such as dengue serotype and genotype are associated with ...severe dengue (SD). However, none of the studies have investigated the relationship between DENV‐1 genotypes and SD. To understand the association between DENV‐1 genotypes and SD, the clinical manifestations of patients infected with different genotypes were investigated. A total of 122 patients with confirmed DENV‐1 genotype infection were recruited for this study. The clinical manifestations, laboratory tests, and levels of inflammatory mediator factors were statistically analyzed to investigate the characteristics of clinical manifestations and immune response on the DENV‐1 genotype. In the case of DENV‐1 infection, the incidence of SD with genotype V infection was significantly higher than that with genotype I infection. Meanwhile, patients infected with genotype V were more common in ostealgia and bleeding significantly. In addition, levels of inflammatory mediator factors including IFN‐γ, TNF‐α, IL‐10, and soluble vascular cell adhesion molecule 1 were higher in patients with SD infected with genotype V. Meanwhile, the concentrations of regulated upon activation normal T‐cell expressed and secreted and growth‐related gene alpha were lower in patients with SD infected with genotype V. The higher incidence of SD in patients infected with DENV‐1 genotype V may be attributed to elevated cytokines and adhesion molecules, along with decreased chemokines.
Hepatocellular carcinoma (HCC) has a complex and changeable tumor microenvironment. Despite emerging evidence focusing on autophagy process within immune cells, the function and regulatory mechanism ...of macrophage autophagy in tumor progression remains unclear. Our results of multiplex-immunohistochemistry and RNA-sequencing identified the reduced levels of autophagy in tumor macrophages in the HCC microenvironment, associated with a poor prognosis and increased microvascular metastasis in HCC patients. Specifically, HCC suppressed the macrophage autophagy initiation through the up-regulation of mTOR and ULK1 phosphorylation at Ser757. Knockdown of autophagy-related proteins to further inhibit autophagy significantly boosted the metastatic potential of HCC. Mechanistically, the accumulation of NLRP3 inflammasome mediated by autophagy inhibition promoted the cleavage, maturation, and release of IL-1β, which facilitated the HCC progression, eventually accelerating HCC metastasis via the epithelial-mesenchymal transition. Autophagy inhibition provoked macrophage self-recruitment through the CCL20-CCR6 signaling was also a crucial account of HCC progression. Recruited macrophages mediated the cascade amplification of IL-1β and CCL20 to form a novel pro-metastatic positive feedback loop through promoting HCC metastasis and increased macrophage recruitment, respectively. Notably, targeting IL-1β/IL-1 receptor signaling impaired lung metastasis induced by macrophage autophagy inhibition in a mice HCC lung metastasis model. In summary, this study highlighted that inhibition of tumor macrophage autophagy facilitated HCC progression by increasing IL-1β secretion via NLRP3 inflammasome accumulation and by macrophage self-recruitment through the CCL20 signaling pathway. Interruption of this metastasis-promoting loop by IL-1β blockade may provide a promising therapeutic strategy for HCC patients.
Increasing evidence highlights the potential role of long non-coding RNAs (lncRNAs) in the biological behaviors of renal cell carcinoma (RCC). Here, we explored the mechanism of AGAP2-AS1 in the ...occurrence and development of clear cell RCC (ccRCC) involving IGF2BP3/miR-9-5p/THBS2.
The expressions of AGAP2-AS1, IGF2BP3, miR-9-5p, and THBS2 and their relationship were analyzed by bioinformatics. The targeting relationship between AGAP2-AS1 and miR-9-5p and between miR-9-5p and THBS2 was evaluated with their effect on cell biological behaviors and macrophage polarization assayed. Finally, we tested the effect of AGAP2-AS1 on ccRCC tumor formation in xenograft tumors.
IGF2BP3 could stabilize AGAP2-AS1 through m6A modification. AGAP2-AS1 was highly expressed in ccRCC tissues and cells. The lentivirus-mediated intervention of AGAP2-AS1 induced malignant behaviors of ccRCC cells and led to M2 polarization of macrophages. In addition, THBS2 promoted M2 polarization of macrophages by activating the PI3K/AKT signaling pathway. AGAP2-AS1 could directly bind with miR-9-5p and promote the expression of THBS2 downstream of miR-9-5p. These results were further verified by in vivo experiments.
AGAP2-AS1 stabilized by IGF2BP3 competitively binds to miR-9-5p to up-regulate THBS2, activating the PI3K/AKT signaling pathway and inducing macrophage M2 polarization, thus facilitating the development of RCC.
In this paper, we study the polarization of a gravitational wave (GW) emitted by an astrophysical source at a cosmic distance propagating through the Friedmann-Lemaître-Robertson-Walk (FLRW) ...universe. By considering the null geodesic deviations, we first provide a definition of the polarization of the GW in terms of the Weyl scalars with respect to a parallel-transported frame along the null geodesics, and then show explicitly that, due to different effects of the expansion of the universe on the two polarization modes, the so-called “+” and “×” modes, the polarization angle of the GW changes generically, when it is propagating through the curved background. More precisely, due to the presence of the matter field of the FLRW background, both of the “×” and “+” modes can get amplified or diluted, depending on their waveforms, so in principle the effects to the “×” modes are different from those to the “+” modes. As a result, the polarization angle will change along the wave path, regardless of which source it is. As a concrete example, we directly compute the polarization angle in a binary system, and show that different epochs, radiation-, matter- and Λ-dominated, have different effects on the polarization. In particular, for a GW emitted by a binary system, we find explicitly the relation between the change of the polarization angle |Δφ| and the redshift zs of the source in different epochs. In the ΛCDM model, we find that the order of |Δφ|η0F is typically O(10−3) to O(103), depending on the values of zs, where η0 is the (comoving) time of the current universe, and F≡(52561τobs)3/8(GNMc)−5/8 with τobs and Mc being, respectively, the time to coalescence in the observer's frame and the chirp mass of the binary system. The typical value of |Δφ| for LIGO-Virgo sources is 10−21. Hence, it may not be easily detected with current detectors.
The gut microbiota of amphibians is affected by exogenous and endogenous factors. We performed a comprehensive analysis using high-throughput sequencing technology and functional predictions and ...observed general changes in the gut microbiota of frogs in different growth stages, seasons, and growth environments. There were no significant differences in microbial richness and diversity between juvenile and adult wild frogs, between the summer and autumn groups of captive frogs, or between wild and captive frogs. There were significant differences in the gut microbiota community structure of
between the summer and autumn groups of captive frogs and between wild and captive
, whereas the differences between juvenile and adult wild frogs were not significant. The dominant gut bacterial phyla in frogs from both captive and wild environments included Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Linear discriminant effect size (LEfSe) analysis showed that Bacteroidetes and Firmicutes were significantly enriched in captive and wild
, respectively linear discriminant analysis (LDA > 4). The core operational taxonomical units (OTUs) that were found in >90% of all frogs tested encompassed 15 core OTUs. The captive frogs exhibited 15 core OTUs in addition to the above overall core microbiota, whereas the wild frogs exhibited 19 core OTUs in addition to the above overall core microbiota. Predictions made using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) suggested that eleven KEGG pathways, such as infectious diseases, immune system diseases, metabolism, metabolism of other amino acids, metabolism of cofactors and vitamins, metabolism of terpenoids and polyketides, neurodegenerative diseases, and transport and catabolism, were enriched in captive frogs. The relative abundance of several red-leg-syndrome-related pathogens increased significantly in captive frogs compared with that in wild frogs. To our knowledge, this is the first study on the effects of individual seasons and captivity on the gut microbiota of frogs.
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