Considered as a sensitive indicator of climate change, lake ice phenology can have significant influences on regional climate by affecting lake-atmosphere energy and water exchange. However, in situ ...measurements of ice phenology events are quite limited over high-elevation lakes on the Tibetan Plateau, where satellite monitoring can make up such deficiency. In this study, by a combination of AMSR-E (2002-2011) and AMSR-2 (2012-2021) passive microwave data, MODIS optimal products and in situ measurements of temperature profiles in four lakes, the ice phenology events of 40 high-elevation large lakes were derived and their inter-annual trends and influencing factors were analyzed. The freeze-up start date (FUS) mainly occurs in November-December with an average date of 9 December and the break-up end date (BUE) is concentrated in April-May with a multi-year average of 5 May. Under climate warming, 24 of the 34 (70.6%) lakes show delayed FUS at an average trend of 0.35 days/year, and 7 (20.6%) lakes show advanced BUE (rate of change CR = -0.17 days/year). The average ice coverage duration (ID) was 147 days, and 13 (38.2%) lakes shortened ID at an average rate of -0.33 days/year. By synthesizing other ice phenology products, we obtained the assembled products of lake ice phenology, and found that air temperature dominates during the freeze-thaw process, with a higher dependence of BUE than that of FUS on air temperature.
Surface texture and nitride coating have been proved as effective ways to improve the tribological properties of biomedical titanium alloys. However, the influence of surface texture and nitride ...coating on cells behavior, especially on the polarization of macrophages, was rarely reported. In this work, Ti-6Al-4V parts with designed rhombus surface texture were successfully prepared by selective laser melting process. Followed by post heating treatment in N2, uniform and dense nitride coatings on the textured surfaces consisted of TiN, Ti2N, TiN0.9 and N-containing solid solution with a thickness of ~5 μm were generated. The combination of surface texture and nitride coating reduced the frictional coefficient from 0.343 to 0.166, and significantly improved the wear resistance of the substrate. The nitride coating promoted the adhesion and proliferation of MC3T3-E1 cells in the early stages (1 d and 3 d). Textured surfaces provided larger area for cells growth that encouraged the cell adhesion and early spread. The significant increasing of the expression of Arg-1 and the ratio of CD206 positive cells (M2 phenotype) comparing with the uncoated group indicated that the nitride coating promoted the macrophages (Raw264.7 cells) polarization into anti-inflammatory type after co-culturing for 24 h. Surface texture combined with nitride coating further increased the ratio of CD206 positive cells and also reduced the inflammatory factors releasing.
•Designable textured nitride coating prepared by SLM followed with post heating treatment in N2•Significant reduction of the frictional coefficient and wear volume by textured nitride coating•Macrophages polarization into anti-inflammatory phenotype through nitride coating and 3D-printed texture
Despite remarkable clinical efficacy of immune checkpoint blockade (ICB) in cancer treatment, ICB benefits for triple-negative breast cancer (TNBC) remain limited. Through pooled in vivo CRISPR ...knockout (KO) screens in syngeneic TNBC mouse models, we found that deletion of the E3 ubiquitin ligase Cop1 in cancer cells decreases secretion of macrophage-associated chemokines, reduces tumor macrophage infiltration, enhances anti-tumor immunity, and strengthens ICB response. Transcriptomics, epigenomics, and proteomics analyses revealed that Cop1 functions through proteasomal degradation of the C/ebpδ protein. The Cop1 substrate Trib2 functions as a scaffold linking Cop1 and C/ebpδ, which leads to polyubiquitination of C/ebpδ. In addition, deletion of the E3 ubiquitin ligase Cop1 in cancer cells stabilizes C/ebpδ to suppress expression of macrophage chemoattractant genes. Our integrated approach implicates Cop1 as a target for improving cancer immunotherapy efficacy in TNBC by regulating chemokine secretion and macrophage infiltration in the tumor microenvironment.
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•In vivo CRISPR screens identify new immune targets regulating the tumor microenvironment•Cop1 knockout in cancer cells enhances anti-tumor immunity•Cop1 modulates chemokine secretion and macrophage infiltration into tumors•Cop1 targets C/ebpδ degradation via Trib2 and influences ICB response
Large-scale in vivo CRISPR screens reveal that Cop1 knockout in cancer cells stabilizes C/ebpδ protein, suppressing macrophage infiltration and enhancing anti-tumor immunity.
Tumor-infiltrating B cells are an important component in the microenvironment but have unclear anti-tumor effects. We enhanced our previous computational algorithm TRUST to extract the B cell ...immunoglobulin hypervariable regions from bulk tumor RNA-sequencing data. TRUST assembled more than 30 million complementarity-determining region 3 sequences of the B cell heavy chain (IgH) from The Cancer Genome Atlas. Widespread B cell clonal expansions and immunoglobulin subclass switch events were observed in diverse human cancers. Prevalent somatic copy number alterations in the MICA and MICB genes related to antibody-dependent cell-mediated cytotoxicity were identified in tumors with elevated B cell activity. The IgG3-1 subclass switch interacts with B cell-receptor affinity maturation and defects in the antibody-dependent cell-mediated cytotoxicity pathway. Comprehensive pancancer analyses of tumor-infiltrating B cell-receptor repertoires identified novel tumor immune evasion mechanisms through genetic alterations. The IgH sequences identified here are potentially useful resources for future development of immunotherapies.
Numerous previous studies have pointed out that the South Asia monsoon (SAM) contributes most moisture to the southern Tibetan Plateau, whilst the moisture over the Northern Tibetan Plateau (NTP) is ...supplied by the westerlies, but the moisture sources for extreme precipitation events remain unclear. In this study, the tracking of external moisture sources was performed on ten extreme precipitation events over each of six target subregions of the NTP during the summer of 2010–2018. We found that the SAM provided most of the external moisture for extreme precipitation events in the NTP, except for the largest contribution from East Asia to extreme precipitation in the easternmost subregion. The moisture carried by westerly winds is the second foreign source over the western NTP. In addition, more than 40% of the NTP extreme precipitation events occurred under the synergy of weak westerlies and enhanced SAM, and these events have a longer duration than others. Thus, SAM plays a key role in moisture transport for the extreme precipitation events over the NTP, even though its contribution to the climatological moisture is not significant.
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•A novel iron-based shape memory alloy was successfully deposited by wire and arc additive manufacturing.•As-deposited material was predominantly composed by FCC γ phase with a ...columnar dendritic morphology.•High mechanical performance was observed for yield strength, fracture stress, elongation, cyclic repetibility and hardness.•Uniaxial loading induced the FCC γ → HCP ε phase transformation and resulted in a ductile fracture.
Shape memory alloys (SMA) are a class of smart materials with inherent shape memory and superelastic characteristics. Unlike other SMAs, iron-based SMAs (Fe-SMA) offer cost-effectiveness, weldability, and robust mechanical strength for the construction industry. Thus, applying these promising materials to advanced manufacturing processes is of considerable industrial and academic relevance. This study aims to present a pioneer application of a Fe–Mn–Si–Cr–Ni–V-C SMA to arc-based directed energy deposition additive manufacturing, namely wire and arc additive manufacturing (WAAM), examining the microstructure evolution and mechanical/functional response. The WAAM-fabricated Fe-SMAs presented negligible porosity and high deposition efficiency. Microstructure characterization encompassing electron microscopy and high energy synchrotron X-ray diffraction revealed that the as-deposited material is primarily composed by γ FCC phase with modest amounts of VC, ε and σ phases. Tensile and cyclic testing highlighted the Fe-SMA's excellent mechanical and functional response. Tensile testing revealed a yield strength and fracture stress of 472 and 821 MPa, respectively, with a fracture strain of 26%. After uniaxial tensile loading to fracture, the γ → ε phase transformation was clearly evidenced with post-mortem synchrotron X-ray diffraction analysis. The cyclic stability during 100 load/unloading cycles was also evaluated, showcasing the potential applicability of the fabricated material for structural applications.
Cancer results from a breakdown of normal gene expression control, so the study of gene regulation is critical to cancer research. To gain insight into the transcriptional and epigenetic factors ...regulating abnormal gene expression patterns in cancers, we developed the Cistrome Cancer web resource (http://cistrome.org/CistromeCancer/). We conducted the systematic integration and modeling of over 10,000 tumor molecular profiles from The Cancer Genome Atlas (TCGA) with over 23,000 ChIP-seq and chromatin accessibility profiles from our Cistrome collection. The results include reconstruction of functional enhancer profiles, "super-enhancer" target genes, as well as predictions of active transcription factors and their target genes for each TCGA cancer type. Cistrome Cancer reveals novel insights from integrative analyses combining chromatin profiles with tumor molecular profiles and will be a useful resource to the cancer gene regulation community.
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Circular RNAs (circRNAs) have been shown to be essential for the emergence and growth of different cancers. However, further research is required to validate the function of circRNA in glioblastoma ...(GBM).
CircNDC80 expression in both normal brain tissues (NBTs) and glioma tissues was determined using real-time PCR. The impact of circNDC80 on GBM cell proliferation, migration, and invasion was then confirmed by CCK-8, colony formation, EdU incorporation, Transwell, and wound healing assays. To determine how circNDC80 affects the capacity of glioma stem cells (GSCs) to maintain their stemness and self-renewal, a CellTiter-Glo assay, clonogenic assay and extreme limiting dilution assay were utilized. To ascertain the impact of circNDC80 in vivo, intracranial xenograft models were established.
When compared to NBT, glioblastoma tissue had a higher level of circNDC80 expression. In functional assays, circNDC80 promoted glioblastoma cell proliferation, migration, and invasion, while sustaining the stemness and fostering the self-renewal of glioma stem cells. In addition, a dual luciferase reporter assay and circRIP were used to verify that circNDC80 simultaneously affects the expression of ECE1 mRNA by sponging miR-139-5p, and a rescue experiment was used to verify the above results further.
According to our research, circNDC80 is an oncogenic factor that promotes glioblastoma through the miR-139-5p/ECE1 pathway. This implies that circNDC80 may be employed as a novel therapeutic target and a possible predictive biomarker.
•Heterologous expression of two nitrite reductase subunits from Acidovorax wautersii.•Enzymatic activity range of temperature (20−60 °C) and pH (5.0–9.0).•Molecular dynamics simulations indicate ...specific amino residues of subunits.•Nitrite ion interacts with active site of enzyme by forming ligand hydrogen bonds.
Large accumulation of nitrate in soil has resulted in soil salinization. Nitrate and nitrite reduction are of great importance for nitrogen assimilation, and understanding the specific roles of each participating reductase is necessary to describe the biochemical balance that dictates the bacteria responses to their environments. The genes encoding assimilatory nitrite reductase from Acidovorax wautersii QZ-4 were cloned and over-expressed in Escherichia coli. The molecular mass of over-expressed nitrite reductase was 91.75 kDa and 12.40 kDa for large subunit NirB and small subunit NirD, respectively. The purified recombinant enzyme showed broad activity range of temperature (20−60 °C) and pH (5.0–9.0). The optimum electron donor was MV + Na2S2O4, and NADH can be used as physiological electron donor. It was found that two important amino residues in NirD, Arg 90 and Arg 24 are critical for interaction with NirB, meanwhile, two amino residues of NirB such as Arg 257 and Asp 333 are found to be critical to interact with NirD. The nitrite ion was responsible for the unique interaction with the active site of NirB with the ligand quintuple hydrogen bonds with Arg 44 and Arg 128. These findings constitute a solid basis for valuable application of nitrite reduction in polluted environment, and give a reasonable explanation for the modes of action between enzyme from A. wautersii QZ-4 and nitrite ion.
Clutter cancellation and long time integration are two vital steps for global navigation satellite system (GNSS)-based bistatic radar target detection. The former eliminates the influence of direct ...and multipath signals on the target detection performance, and the latter improves the radar detection range. In this paper, the extensive cancellation algorithm (ECA), which projects the surveillance channel signal in the subspace orthogonal to the clutter subspace, is first applied in GNSS-based bistatic radar. As a result, the clutter has been removed from the surveillance channel effectively. For long time integration, a modified version of the Fourier transform (FT), called long-time integration Fourier transform (LIFT), is proposed to obtain a high coherent processing gain. Relative acceleration (RA) is defined to describe the Doppler variation results from the motion of the target and long integration time. With the estimated RA, the Doppler frequency shift compensation is carried out in the LIFT. This method achieves a better and robust detection performance when comparing with the traditional coherent integration method. The simulation results demonstrate the effectiveness and advantages of the proposed processing method.
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