Abstract
Background
Tertiary lymphoid structures (TLSs), organizationally resemble lymph nodes, are frequently present in breast cancer (BCa). It is usually, but not always, associated with a ...positive prognosis or immunotherapy response in cancer patients. This meta-analysis was performed to assess the prognostic and clinical impact of TLSs in BCa.
Methods
We conducted a systematic search in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and WanFang Database to obtain eligible research data up to May 30, 2021. This meta-analysis is focusing on the studies evaluated the prognostic value of TLSs and the associated clinicopathologic indicators, related gene expression and survival. STATA software 16.0 software was used to assess the prognostic significance and clinical impact of TLSs.
Results
Nine studies involved with 2281 cases were incorporated in this meta-analysis, in which four of them evaluated the prognostic value of TLSs. There are 6 studies assessed the relationship of TLSs and 4 studies investigated the clinicopathologic parameters as well as the key gene expression, respectively. The results showed the presence of TLSs were predicting a better OS (HR = 0.61, 95% CI: 0.51–0.73,
p
< 0.001) and DFS (HR = 0.40, 95% CI: 0.17–0.93,
p
< 0.001) of BCa patients. It also revealed that the presence of TLSs was significantly correlated with tumor differentiation (
p
< 0.001), pTNM stage (
p
< 0.001), lymph node metastasis (
p
< 0.001), and TILs density (
p
< 0.001) of BCa, and the expression of Her2 (
p
< 0.001), ER (
p
< 0.001), PR (
p
< 0.001) and Ki67 (
p
= 0.009) of the tumor cell.
Conclusion
Our results indicated that high levels of TLSs could predict a favorable prognosis for BCa. Moreover, the TLSs were significantly correlated with the clinicopathological indicators and the critical gene expression of BCa, indicating its potential clinical impact on BCa patients.
In this study, 2-benzyl-10a-(1
-pyrrol-2-yl)-2,3-dihydropyrazino1,2-
indole-1,4,10(10a
)-trione (DHPITO), a previously identified inhibitor against hepatocellular carcinoma cells, is shown to exert ...its cytotoxic effects by suppressing the proliferation and growth of CRC cells. An investigation of its molecular mechanism confirmed that the cytotoxic activity of DHPITO is mediated through the targeting of microtubules with the promotion of subsequent microtubule polymerisation. With its microtubule-stabilising ability, DHPITO also consistently arrested the cell cycle of the CRC cells at the G2/M phase by promoting the phosphorylation of histone 3 and the accumulation of EB1 at the cell equator, reduced the levels of CRC cell migration and invasion, and induced cellular apoptosis. Furthermore, the compound could suppress both tumour size and tumour weight in a CRC xenograft model without any obvious side effects. Taken together, the findings of the present study reveal the antiproliferative and antitumour mechanisms through which DHPITO exerts its activity, indicating its potential as a putative chemotherapeutic agent and lead compound with a novel structure.
Due to the single-molecule sensitivity and the capability of chemical fingerprints recognition, surface-enhanced Raman scattering (SERS) has been an attractive analytical technique used in various ...fields. However, SERS sensing still suffers from several problems, including the heterogeneous adsorption of molecules on SERS substrates, the spectral fluctuation of molecules, the photo/chemical reactions of molecules in direct contact with metal, and the continuum spectral background originated from fluorescence or photocarbonization. Such problems greatly hinder its practical applications, in particular, in SERS quantification. Graphene, the star of the two-dimensional (2D) materials family, can be used for Raman enhancement, termed as graphene-based surface-enhanced Raman scattering (G-SERS). In this review, we will introduce the discovery of graphene-enhanced Raman scattering (GERS), the chemical enhancement, and its extension to other 2D materials beyond graphene. Then we will concentrate on graphene-based SERS toward analytical applicationsfrom graphene-veiled SERS to G-SERS tape for quantitative analysis.
PI3K/Akt signaling is activated in cancers and governs tumor initiation and progression, but how Akt is activated under diverse stresses is poorly understood. Here we identify AMPK as an essential ...regulator for Akt activation by various stresses. Surprisingly, AMPK is also activated by growth factor EGF through Ca2+/Calmodulin-dependent kinase and is essential for EGF-mediated Akt activation and biological functions. AMPK phosphorylates Skp2 at S256 and promotes the integrity and E3 ligase activity of Skp2 SCF complex leading to K63-linked ubiquitination and activation of Akt and subsequent oncogenic processes. Importantly, AMPK-mediated Skp2 S256 phosphorylation promotes breast cancer progression in mouse tumor models, correlates with Akt and AMPK activation in breast cancer patients, and predicts poor survival outcomes. Finally, targeting AMPK-mediated Skp2 S256 phosphorylation sensitizes cells to anti-EGF receptor targeted therapy. Our study sheds light on how stress and EGF induce Akt activation and new mechanisms for AMPK-mediated oncogenesis and drug resistance.
Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a ...therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.
One great challenge in understanding the history of life is resolving the influence of environmental change on biodiversity. Simulated annealing and genetic algorithms were used to synthesize data ...from 11,000 marine fossil species, collected from more than 3000 stratigraphic sections, to generate a new Cambrian to Triassic biodiversity curve with an imputed temporal resolution of 26 ± 14.9 thousand years. This increased resolution clarifies the timing of known diversification and extinction events. Comparative analysis suggests that partial pressure of carbon dioxide (
co
) is the only environmental factor that seems to display a secular pattern similar to that of biodiversity, but this similarity was not confirmed when autocorrelation within that time series was analyzed by detrending. These results demonstrate that fossil data can provide the temporal and taxonomic resolutions necessary to test (paleo)biological hypotheses at a level of detail approaching those of long-term ecological analyses.
As an important medium of intercellular communication, exosomes play an important role in information transmission between tumor cells and their microenvironment. Tumor metastasis is a serious ...influencing factor for poor treatment effect and shortened survival. Lung cancer is a major malignant tumor that seriously threatens human health. The study of the underlying mechanisms of exosomes in tumor genesis and development may provide new ideas for early and effective diagnosis and treatment of lung cancer metastasis. Many studies have shown that tumor-derived exosomes promote lung cancer development through a number of processes. By promoting epithelial-mesenchymal transition of tumor cells, they induce angiogenesis, establishment of the pretransfer microenvironment, and immune escape. This understanding enables researchers to better understand the mechanism of lung cancer metastasis and explore new treatments for clinical application. In this article, we systematically review current research progress of tumor-derived exosomes in metastasis of lung cancer. Although positive progress has been made toward understanding the mechanism of exosomes in lung cancer metastasis, systematic basic research and clinical translational research remains lacking and are needed to translate our scientific understanding toward applications in the clinical diagnosis and treatment of lung cancer metastasis in the near future.
Paclitaxel is highly effective at killing many malignant tumors; however, the development of drug resistance is common in clinical applications. The issue of overcoming paclitaxel resistance is a ...difficult challenge at present. In this study, we developed nano drugs to treat paclitaxel-resistant lung adenocarcinoma. We selected cabazitaxel and β-elemene, which have fewer issues with drug resistance, and successfully prepared cabazitaxel liposome, β-elemene liposome and cabazitaxel-β-elemene complex liposome with good flexibility. The encapsulation efficiencies of cabazitaxel and β-elemene in these liposomes were detected by precipitation microfiltration and microfiltration centrifugation methods, respectively. Their encapsulation efficiencies were all above 95%. The release rates were detected by a dialysis method. The release profiles of cabazitaxel and β-elemene in these liposomes conformed to the Weibull equation. The release of cabazitaxel and β-elemene in the complex liposome were almost synchronous. The pharmacodynamics study showed that cabazitaxel flexible liposome and β-elemene flexible liposome were relatively good at overcoming paclitaxel resistance on paclitaxel-resistant lung adenocarcinoma. As the flexible complex liposome, the dosage of cabazitaxel could be reduced to 25% that of the cabazitaxel injection while retaining a similar therapeutic effect. It showed that β-elemene can replace some of the cabazitaxel, allowing the dosage of cabazitaxel to be reduced, thereby reducing the drug toxicity.
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•We investigated antibiotic resistome during manure composting by metagenomics.•Moisture was the key environmental factor over composting.•Composting significantly reduced the ...relative abundance of ARGs and MGEs.•Actinobacteria was the primary potential host of ARGs over composting.•Bacterial community and BMRGs profiles structured the antibiotic resistome.
Composting has been widely used to turn livestock manure into organic fertilizer. However, livestock manure contains various contaminants including antibiotics and antibiotic resistance genes (ARGs). Here we investigated the variation of antibiotic resistome and its influencing factors during a commercial livestock manure composting. The results showed that composting could effectively reduce the relative abundance of ARGs and mobile genic elements (MGEs). As the dominant phylum in the composting samples, the key potential bacterial host of ARGs were Actinobacteria such as Leucobacter, Mycobacterium and Thermomonosporaceae unclassified. Meanwhile, Legionella pneumophila, Staphylococcus saprophyticus, Haemophilus ducreyi and Siccibacter turicensis may be the key potential pathogenic host of ARGs because of their co-occurrence with ARG subtypes. Redundancy analysis showed that the dissipation of ARGs during composting was linked to various environmental factors such as moisture. Bacterial succession as well as profile of biocide and metal resistance genes (BMRGs) were the determinants which constructed the antibiotic resistome during manure composting. However, the residues of ARGs and pathogens in compost products may still pose risks to human and crops after fertilization.
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