High-entropy alloys are a class of materials that contain five or more elements in near-equiatomic proportions
. Their unconventional compositions and chemical structures hold promise for achieving ...unprecedented combinations of mechanical properties
. Rational design of such alloys hinges on an understanding of the composition-structure-property relationships in a near-infinite compositional space
. Here we use atomic-resolution chemical mapping to reveal the element distribution of the widely studied face-centred cubic CrMnFeCoNi Cantor alloy
and of a new face-centred cubic alloy, CrFeCoNiPd. In the Cantor alloy, the distribution of the five constituent elements is relatively random and uniform. By contrast, in the CrFeCoNiPd alloy, in which the palladium atoms have a markedly different atomic size and electronegativity from the other elements, the homogeneity decreases considerably; all five elements tend to show greater aggregation, with a wavelength of incipient concentration waves
as small as 1 to 3 nanometres. The resulting nanoscale alternating tensile and compressive strain fields lead to considerable resistance to dislocation glide. In situ transmission electron microscopy during straining experiments reveals massive dislocation cross-slip from the early stage of plastic deformation, resulting in strong dislocation interactions between multiple slip systems. These deformation mechanisms in the CrFeCoNiPd alloy, which differ markedly from those in the Cantor alloy and other face-centred cubic high-entropy alloys, are promoted by pronounced fluctuations in composition and an increase in stacking-fault energy, leading to higher yield strength without compromising strain hardening and tensile ductility. Mapping atomic-scale element distributions opens opportunities for understanding chemical structures and thus providing a basis for tuning composition and atomic configurations to obtain outstanding mechanical properties.
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Most mechanisms used for strengthening crystalline materials, e.g. introducing crystalline interfaces, lead to the reduction of ductility. An additive manufacturing process – ...selective laser melting breaks this trade-off by introducing dislocation network, which produces a stainless steel with both significantly enhanced strength and ductility. Systematic electron microscopy characterization reveals that the pre-existing dislocation network, which maintains its configuration during the entire plastic deformation, is an ideal “modulator” that is able to slow down but not entirely block the dislocation motion. It also promotes the formation of a high density of nano-twins during plastic deformation. This finding paves the way for developing high performance metals by tailoring the microstructure through additive manufacturing processes.
Cancer-associated fibroblasts (CAFs) constitute a prominent component of the tumor microenvironment and play critical roles in cancer progression and drug resistance. Although recent studies indicate ...CAFs may consist of several CAF subtypes, the breadth of CAF heterogeneity and functional roles of CAF subtypes in cancer progression remain unclear. In this study, we implemented a cell-type deconvolutional approach to comprehensively characterize cell-type alternations across 18 cancer types from The Cancer Genome Atlas (TCGA). Pan-cancer survival analysis using deconvoluted CAF subtypes revealed myofibroblastic CAF (myCAF) composition as a poor prognostic factor in nine cancer types. Patients with higher myCAF compositions tend to have worse response to six antineoplastic drugs predicted by a lncRNA-based Elastic Net prediction model (LENP). In addition, integrative mutational analysis identified 14 and 413 genes associated with the differentiation degree of myCAF and inflammatory CAF (iCAF), respectively, with significant enrichment of genes involved in fibroblast and extracellular matrix (ECM)-related pathways. In summary, our findings systematically illustrated the complex roles of CAF subtypes in patient prognosis and drug response, and identified putative driver genes in CAF-subtype differentiation. These results provided novel therapeutic perspectives for targeting CAF subtypes in tumor microenvironment and arranging treatment scheme based on the CAF compositions in different cancer types.
Wuhan was the first city to adopt the lockdown measures to prevent COVID-19 spreading, which improved the air quality accordingly. This study investigated the variations in chemical compositions, ...source contributions, and regional transport of fine particles (PM2.5) during January 23–February 22 of 2020, compared with the same period in 2019. The average mass concentration of PM2.5 decreased from 72.9 μg m−3 (2019) to 45.9 μg m−3 (2020), by 27.0 μg m−3. It was predominantly contributed by the emission reduction (92.0%), retrieved from a random forest tree approach. The main chemical species of PM2.5 all decreased with the reductions ranging from 0.85 μg m−3 (chloride) to 9.86 μg m−3 (nitrate) (p < 0.01). Positive matrix factorization model indicated that the mass contributions of seven PM2.5 sources all decreased. However, their contribution percentages varied from −11.0% (industrial processes) to 8.70% (secondary inorganic aerosol). Source contributions of PM2.5 transported from potential geographical regions showed reductions with mean values ranging from 0.22 to 4.36 μg m−3. However, increased contributions of firework burning, secondary inorganic aerosol, road dust, and vehicle emissions from transboundary transport were observed. This study highlighted the complex and nonlinear response of chemical compositions and sources of PM2.5 to air pollution control measures, suggesting the importance of regional-joint control.
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•Differences in PM2.5 chemical species and sources since lockdown were reported.•Primary emission reduced while secondary formation enhanced since lockdown.•Emission reduction dominated the improvement of air quality in Wuhan during lockdown.
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Technologically important mechanical properties of engineering materials often degrade at low temperatures. One class of materials that defy this trend are CrCoNi-based medium- and ...high-entropy alloys, as they display enhanced strength, ductility, and toughness with decreasing temperature. Here we show, using in situ straining in the transmission electron microscope at 93 K (−180 °C) that their exceptional damage tolerance involves a synergy of deformation mechanisms, including twinning, glide of partials and full dislocations, extensive cross-slip, and multiple slip activated by dislocation and grain-boundary interactions. In particular, massive cross-slip occurs at the early stages of plastic deformation, thereby promoting multiple slip and dislocation interactions. These results indicate that the reduced intensity of thermal activation of defects at low temperatures and the required increase of applied stress for continued plastic flow, together with high lattice resistance, play a pivotal role in promoting the concurrent operation of multiple deformation mechanisms, which collectively enable the outstanding mechanical properties of these alloys.
Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis ...factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.
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•TNF-α stabilizes cancer cell PD-L1 in response to chronic inflammation•Activation of NF-κB by TNF-α induces CSN5 expression leading to PD-L1 stabilization•CSN5 enzyme activity controls T cell suppression via PD-L1 deubiquitination•Destabilization of PD-L1 by CSN5 inhibitor curcumin benefits anti-CTLA4 therapy
Lim et al. show that inflammation increases PD-L1 expression in tumors through TNF-α-mediated activation of NF-κB, leading to transactivation of CSN5. CSN5 reduces PD-L1 ubiquitination and stabilizes it. Inhibition of CSN5 cooperates with anti-CTLA4 to enhance anti-tumor T cell function and reduce tumor growth.
Extracellular interaction between programmed death ligand-1 (PD-L1) and programmed cell death protein-1 (PD-1) leads to tumour-associated immune escape. Here we show that the immunosuppression ...activity of PD-L1 is stringently modulated by ubiquitination and N-glycosylation. We show that glycogen synthase kinase 3β (GSK3β) interacts with PD-L1 and induces phosphorylation-dependent proteasome degradation of PD-L1 by β-TrCP. In-depth analysis of PD-L1 N192, N200 and N219 glycosylation suggests that glycosylation antagonizes GSK3β binding. In this regard, only non-glycosylated PD-L1 forms a complex with GSK3β and β-TrCP. We also demonstrate that epidermal growth factor (EGF) stabilizes PD-L1 via GSK3β inactivation in basal-like breast cancer. Inhibition of EGF signalling by gefitinib destabilizes PD-L1, enhances antitumour T-cell immunity and therapeutic efficacy of PD-1 blockade in syngeneic mouse models. Together, our results link ubiquitination and glycosylation pathways to the stringent regulation of PD-L1, which could lead to potential therapeutic strategies to enhance cancer immune therapy efficacy.
Currently there is no highly specific and sensitive marker to identify breast cancer—the most common malignancy in women. Breast cancer can be categorized as estrogen receptor (ER)/progesterone ...receptor (PR)-positive luminal, human epidermal growth factor receptor 2 (HER2)-positive, or triple-negative breast cancer (TNBC) types based on the expression of ER, PR, and HER2. Although GATA3 is the most widely used tumor marker at present to determine the breast origin, which has been shown to be an excellent marker for ER-positive and low-grade breast cancer, but it does not work well for TNBC with sensitivity as low as <20% in metaplastic breast carcinoma. In the current study, through TCGA data mining we identified trichorhinophalangeal syndrome type 1 (TRPS1) as a specific gene for breast carcinoma across 31 solid tumor types. Moreover, high mRNA level of TRPS1 was found in all four subtypes of breast carcinoma including ER/PR-positive luminal A and B types, HER2-positive type, and basal-type/TNBC. We then analyzed TRPS1 expression in 479 cases of various types of breast cancer using immunochemistry staining, and found that TRPS1 and GATA3 had comparable positive expression in ER-positive (98% vs. 95%) and HER2-positive (87% vs. 88%) breast carcinomas. However, TRPS1 which was highly expressed in TNBC, was significantly higher than GATA3 expression in metaplastic (86% vs. 21%) and nonmetaplastic (86% vs. 51%) TNBC. In addition, TRPS1 expression was evaluated in 1234 cases of solid tumor from different organs. In contrast to the high expression of GATA3 in urothelial carcinoma, TRPS1 showed no or little expression in urothelial carcinomas or in other tumor types including lung adenocarcinoma, pancreatic adenocarcinoma, colon and gastric adenocarcinoma, renal cell carcinoma, melanoma, and ovarian carcinoma. These findings suggest that TRPS1 is a highly sensitive and specific marker for breast carcinoma and can be used as a great diagnostic tool, especially for TNBC.
•Magnetic nitrogen-doped carbon nanotube cages (N-CNTCs) were prepared.•Large amount of doped nitrogen increase hydrophilicity and hydrogen bonding.•The sp2-carbon provide strong π-π stacking ...interaction between material and analyte.•The proposed MSPE-HPLC-MS/MS method exhibited high sensitivity and low LOD.•The material was successfully applied for the isolation OA in real aquatic products.
An easy-prepared adsorbent with high stable and good dispersibility is especially valuable for the development of magnetic solid-phase extraction (MSPE) techniques. In this study, magnetic nitrogen-doped carbon nanotube cages (N-CNTCs) were synthesized via direct carbonization of cobalt (II)-containing metal-organic frameworks. During carbonization, cobalt ions inside the MOFs were converted into magnetic functional nanoparticles of N-CNTCs. Simultaneously, large amounts of nitrogen, originating from the organic ligands, were doped into the carbon framework. This unique structure gave the N-CNTCs excellent chemical stability, high affinity, and good dispersibility. The synthesized magnetic N-CNTCs were then used for MSPE of okadaic acid (OA) from aquatic samples. A simple, efficient, and sensitive method for detecting and quantitating OA was developed by combining the above sample pretreatment technique with high-performance liquid chromatography -tandem mass spectrometry (HPLC-MS/MS). The resulting method boasts a linear dynamic range of 3.0–1000.0 pg mL−1 with good linearity (R2 ≥ 0.9994). The limit of detection (LOD) and limit of quantification (LOQ) were 1.3 pg mL−1 and 3.0 pg mL−1, respectively. Several shellfish and seafood samples were analyzed using the developed method, showing satisfactory recoveries (82.0–107.0%) and relative standard deviations (<4.5%). The developed method was also used to investigate the OA distribution in crab tissues. Our results demonstrate that magnetic N-CNTCs are promising adsorbents for providing reliable support for the early warning and tracing to the source of algae toxins.
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