The electronic metal–support interaction (EMSI) plays a crucial role in catalysis as it can induce electron transfer between metal and support, modulate the electronic state of the supported metal, ...and optimize the reduction of intermediate species. In this work, the tailoring of electronic structure of Pt single atoms supported on N‐doped mesoporous hollow carbon spheres (Pt1/NMHCS) via strong EMSI engineering is reported. The Pt1/NMHCS composite is much more active and stable than the nanoparticle (PtNP) counterpart and commercial 20 wt% Pt/C for catalyzing the electrocatalytic hydrogen evolution reaction (HER), exhibiting a low overpotential of 40 mV at a current density of 10 mA cm−2, a high mass activity of 2.07 A mg−1Pt at 50 mV overpotential, a large turnover frequency of 20.18 s−1 at 300 mV overpotential, and outstanding durability in acidic electrolyte. Detailed spectroscopic characterizations and theoretical simulations reveal that the strong EMSI effect in a unique N1−Pt1−C2 coordination structure significantly tailors the electronic structure of Pt 5d states, resulting in promoted reduction of adsorbed proton, facilitated H−H coupling, and thus Pt‐like HER activity. This work provides a constructive route for precisely designing single‐Pt‐atom‐based robust electrocatalysts with high HER activity and durability.
A N‐doped mesoporous hollow carbon sphere supported Pt single atom (Pt1/NMHCS) composite for electrocatalytic hydrogen evolution reaction (HER) is fabricated by a novel strategy. Owing to the strong electronic metal–support interaction in the unique N1−Pt−C2 coordination structure that significantly alters the electronic structure of the Pt 5d states, both the reduction of adsorbed H+ and the generation of H2 are promoted, thus leading to bare‐Pt‐like activity and extraordinary durability for HER.
FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), a 5-fluorouracil (5-FU)-based chemotherapy regimen, is one of most common therapeutic regimens for colorectal cancer. However, intestinal ...mucositis is a common adverse effect for which no effective preventive strategies exist. Moreover, the efficacy and the safety of fecal microbiota transplants (FMT) in cancer patients treated with anti-neoplastic agents are still scant. We investigated the effect of FMT on FOLFOX-induced mucosal injury. BALB/c mice implanted with syngeneic CT26 colorectal adenocarcinoma cells were orally administered FMT daily during and two days after five-day injection of FOLFOX regimen for seven days. Administration of FOLFOX significantly induced marked levels of diarrhea and intestinal injury. FMT reduced the severity of diarrhea and intestinal mucositis. Additionally, the number of goblet cells and zonula occludens-1 decreased, while apoptotic and NF-κB-positive cells increased following FOLFOX treatment. The expression of toll-like receptors (TLRs), MyD88, and serum IL-6 were upregulated following FOLFOX treatment. These responses were attenuated following FMT. The disrupted fecal gut microbiota composition was also restored by FMT after FOLFOX treatment. Importantly, FMT did not cause bacteremia and safely alleviated FOLFOX-induced intestinal mucositis in colorectal cancer-bearing mice. The putative mechanism may involve the gut microbiota TLR-MyD88-NF-κB signaling pathway in mice with implanted colorectal carcinoma cells.
Clearance of apoptotic cells by macrophages prevents excessive inflammation and supports immune tolerance. Here, we examined the effect of blocking apoptotic cell clearance on anti-tumor immune ...response. We generated an antibody that selectively inhibited efferocytosis by phagocytic receptor MerTK. Blockade of MerTK resulted in accumulation of apoptotic cells within tumors and triggered a type I interferon response. Treatment of tumor-bearing mice with anti-MerTK antibody stimulated T cell activation and synergized with anti-PD-1 or anti-PD-L1 therapy. The anti-tumor effect induced by anti-MerTK treatment was lost in Stinggt/gt mice, but not in Cgas−/− mice. Abolishing cGAMP production in Cgas−/− tumor cells, depletion of extracellular ATP, or inactivation of the ATP-gated P2X7R channel also compromised the effects of MerTK blockade. Mechanistically, extracellular ATP acted via P2X7R to enhance the transport of extracellular cGAMP into macrophages and subsequent STING activation. Thus, MerTK blockade increases tumor immunogenicity and potentiates anti-tumor immunity, which has implications for cancer immunotherapy.
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•Antibody blockade of MerTK prevents apoptotic cell clearance by macrophages•MerTK blockade induces tumor-cGAS- and host-STING-dependent type I IFN response•Extracellular ATP facilitates transfer of tumor-derived cGAMP to TAMs via P2X7R•MerTK blockade increases tumor immunogenicity and enhances anti-PD-1/PD-L1 therapy
Zhou et al. generate an antibody that selectively inhibits efferocytosis by the phagocytic receptor MerTK and show that MerTK blockade increases tumor immunogenicity and potentiates anti-tumor immunity via the transfer of tumor-derived cGAMP into tumor-associated macrophages (TAMs) through the ATP-gated channel P2X7R and subsequent STING activation.
Phase transition in thermoelectric (TE) material is a double‐edged sword—it is undesired for device operation in applications, but the fluctuations near an electronic instability are favorable. Here, ...Sb doping is used to elicit a spontaneous composition fluctuation showing uphill diffusion in GeTe that is otherwise suspended by diffusionless athermal cubic‐to‐rhombohedral phase transition at around 700 K. The interplay between these two phase transitions yields exquisite composition fluctuations and a coexistence of cubic and rhombohedral phases in favor of exceptional figures‐of‐merit zT. Specifically, alloying GeTe by Sb2Te3 significantly suppresses the thermal conductivity while retaining eligible carrier concentration over a wide composition range, resulting in high zT values of >2.6. These results not only attest to the efficacy of using phase transition in manipulating the microstructures of GeTe‐based materials but also open up a new thermodynamic route to develop higher performance TE materials in general.
The interplay between phase decomposition and athermal phase transition is leveraged in a Ge–Sb–Te ternary system to enable exquisite microstructure features by strong composition fluctuations and coexistence of rhombohedral and cubic GeTe. Specifically, alloying GeTe with Sb2Te3 significantly suppresses thermal conductivity while retaining eligible carrier concentration over a wide composition range, resulting in high zT values of >2.6.
Real bifunctional electrocatalysts for hydrogen evolution reaction and oxygen evolution reaction have to be the ones that exhibit a steady configuration during/after reaction without irreversible ...structural transformation or surface reconstruction. Otherwise, they can be termed as “precatalysts” rather than real catalysts. Herein, through a strongly atomic metal–support interaction, single-atom dispersed catalysts decorating atomically dispersed Ru onto a nickel–vanadium layered double hydroxide (LDH) scaffold can exhibit excellent HER and OER activities. Both in situ X-ray absorption spectroscopy and operando Raman spectroscopic investigation clarify that the presence of atomic Ru on the surface of nickel–vanadium LDH is playing an imperative role in stabilizing the dangling bond-rich surface and further leads to a reconstruction-free surface. Through strong metal–support interaction provided by nickel–vanadium LDH, the significant interplay can stabilize the reactive atomic Ru site to reach a small fluctuation in oxidation state toward cathodic HER without reconstruction, while the atomic Ru site can stabilize the Ni site to have a greater structural tolerance toward both the bond constriction and structural distortion caused by oxidizing the Ni site during anodic OER and boost the oxidation state increase in the Ni site that contributes to its superior OER performance. Unlike numerous bifunctional catalysts that have suffered from the structural reconstruction/transformation for adapting the HER/OER cycles, the proposed Ru/Ni3V-LDH is characteristic of steady dual reactive sites with the presence of a strong metal–support interaction (i.e., Ru and Ni sites) for individual catalysis in water splitting and is revealed to be termed as a real bifunctional electrocatalyst.
Dysregulated lipid metabolism contributes to cancer progression. Our previous study indicates that long-chain fatty acyl-Co A synthetase (ACSL) 3 is essential for lipid upregulation induced by ...endoplasmic reticulum stress. In this report, we aimed to identify the role of ACSL family in cancer with systematic analysis and in vitro experiment. We explored the ACSL expression using Oncomine database to determine the gene alteration during carcinogenesis and identified the association between ACSL expression and the survival of cancer patient using PrognoScan database. ACSL1 may play a potential oncogenic role in colorectal and breast cancer and play a potential tumor suppressor role in lung cancer. Co-expression analysis revealed that ACSL1 was coexpressed with MYBPH, PTPRE, PFKFB3, SOCS3 in colon cancer and with LRRFIP1, TSC22D1 in lung cancer. In accordance with PrognoScan analysis, downregulation of ACSL1 in colon and breast cancer cell line inhibited proliferation, migration, and anchorage-independent growth. In contrast, increase of oncogenic property was observed in lung cancer cell line by attenuating ACSL1. High ACSL3 expression predicted a better prognosis in ovarian cancer; in contrast, high ACSL3 predicted a worse prognosis in melanoma. ACSL3 was coexpressed with SNUPN, TRIP13, and SEMA5A in melanoma. High expression of ACSL4 predicted a worse prognosis in colorectal cancer, but predicted better prognosis in breast, brain and lung cancer. ACSL4 was coexpressed with SERPIN2, HNRNPCL1, ITIH2, PROCR, LRRFIP1. High expression of ACSL5 predicted good prognosis in breast, ovarian, and lung cancers. ACSL5 was coexpressed with TMEM140, TAPBPL, BIRC3, PTPRE, and SERPINB1. Low ACSL6 predicted a worse prognosis in acute myeloid leukemia. ACSL6 was coexpressed with SOX6 and DARC. Altogether, different members of ACSLs are implicated in diverse types of cancer development. ACSL-coexpressed molecules may be used to further investigate the role of ACSL family in individual type of cancers.
•New fast and fully automatic bone marrow WSI analysis without manual intervention•Identify cells of the most abundant 16 types•Achieve high recall and accuracy greater than 0.9•Provide clinical ...insights of the potential applications of the proposed method•High-speed performance of bone marrow WSI analysis in seconds
Bone marrow (BM) examination is an essential step in both diagnosing and managing numerous hematologic disorders. BM nucleated differential count (NDC) analysis, as part of BM examination, holds the most fundamental and crucial information. However, there are many challenges to perform automated BM NDC analysis on whole-slide images (WSIs), including large dimensions of data to process, complicated cell types with subtle differences. To the authors best knowledge, this is the first study on fully automatic BM NDC using WSIs with 40x objective magnification, which can replace traditional manual counting relying on light microscopy via oil-immersion 100x objective lens with a total 1000x magnification. In this study, we develop an efficient and fully automatic hierarchical deep learning framework for BM NDC WSI analysis in seconds. The proposed hierarchical framework consists of (1) a deep learning model for rapid localization of BM particles and cellular trails generating regions of interest (ROI) for further analysis, (2) a patch-based deep learning model for cell identification of 16 cell types, including megakaryocytes, mitotic cells, and four stages of erythroblasts which have not been demonstrated in previous studies before, and (3) a fast stitching model for integrating patch-based results and producing final outputs. In evaluation, the proposed method is firstly tested on a dataset with a total of 12,426 annotated cells using cross validation, achieving high recall and accuracy of 0.905 ± 0.078 and 0.989 ± 0.006, respectively, and taking only 44 seconds to perform BM NDC analysis for a WSI. To further examine the generalizability of our model, we conduct an evaluation on the second independent dataset with a total of 3005 cells, and the results show that the proposed method also obtains high recall and accuracy of 0.842 and 0.988, respectively. In comparison with the existing small-image-based benchmark methods, the proposed method demonstrates superior performance in recall, accuracy and computational time.
Cephalometric analysis is an essential clinical and research tool in orthodontics for the orthodontic analysis and treatment planning. This paper presents the evaluation of the methods submitted to ...the Automatic Cephalometric X-Ray Landmark Detection Challenge, held at the IEEE International Symposium on Biomedical Imaging 2014 with an on-site competition. The challenge was set to explore and compare automatic landmark detection methods in application to cephalometric X-ray images. Methods were evaluated on a common database including cephalograms of 300 patients aged six to 60 years, collected from the Dental Department, Tri-Service General Hospital, Taiwan, and manually marked anatomical landmarks as the ground truth data, generated by two experienced medical doctors. Quantitative evaluation was performed to compare the results of a representative selection of current methods submitted to the challenge. Experimental results show that three methods are able to achieve detection rates greater than 80% using the 4 mm precision range, but only one method achieves a detection rate greater than 70% using the 2 mm precision range, which is the acceptable precision range in clinical practice. The study provides insights into the performance of different landmark detection approaches under real-world conditions and highlights achievements and limitations of current image analysis techniques.
With the introduction of direct-acting antiviral (DAA) agents, hepatitis C virus (HCV) treatment has dramatically improved. However, there are insufficient data on the benefits of DAA therapy in ...hepatocellular carcinoma (HCC). The purpose of this study was to investigate the outcome of patients who received DAA therapy after HCC treatment. We retrospectively reviewed patients with HCV-related HCC in a single medical center, and the outcome of patients with or without DAA therapy was analyzed. In total, 107 HCC patients were enrolled, of whom 60 had received DAA therapy after treatment for HCC. There were no significant intergroup differences in age, sex, laboratory results, or tumor burden. A more advanced stage was noted in the no DAA group (P = 0.003). In the treatment modality, sorafenib was commonly prescribed in the no DAA group (P = 0.007). The DAA group had a longer overall survival (OS) time than the no DAA group (P<0.001). When stratified by Barcelona Clinic Liver Cancer staging, the DAA group had better OS in the HCC stages 0-A and B-C (P = 0.034 and P = 0.006). There were 35 patients who received DAA therapy after curative HCC therapy. At a median follow-up of 20 months, 37.1% patients had HCC recurrence after DAA therapy. There was no statistical difference in recurrence-free survival between patients receiving and those not receiving DAA (P = 0.278). DAA therapy improved the survival outcome of HCC patients and did not increase recurrent HCC after curative therapy. .
Close proximity between cytotoxic T lymphocytes and tumour cells is required for effective immunotherapy. However, what controls the spatial distribution of T cells in the tumour microenvironment is ...not well understood. Here we couple digital pathology and transcriptome analysis on a large ovarian tumour cohort and develop a machine learning approach to molecularly classify and characterize tumour-immune phenotypes. Our study identifies two important hallmarks characterizing T cell excluded tumours: 1) loss of antigen presentation on tumour cells and 2) upregulation of TGFβ and activated stroma. Furthermore, we identify TGFβ as an important mediator of T cell exclusion. TGFβ reduces MHC-I expression in ovarian cancer cells in vitro. TGFβ also activates fibroblasts and induces extracellular matrix production as a potential physical barrier to hinder T cell infiltration. Our findings indicate that targeting TGFβ might be a promising strategy to overcome T cell exclusion and improve clinical benefits of cancer immunotherapy.
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