Colorectal cancer (CRC) patients, especially those with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) tumors, whose sensitivity to immune checkpoint inhibitors (ICIs) is ...significantly higher than that of patients with microsatellite-stable (MSS)/microsatellite instability-low (MSI-L) tumors, have derived clinical benefits from immunotherapy. Most studies have not systematically evaluated the immune characteristics and immune microenvironments of MSI-H and MSS/MSI-L CRCs. We analyzed the relationship between the MSI status and prognosis of ICI treatment in an immunotherapy cohort. We further used mutation data for the immunotherapy and The Cancer Genome Atlas (TCGA)-CRC colon adenocarcinoma (COAD) + rectum adenocarcinoma (READ) cohorts. For mRNA expression, mutation data analysis of the immune microenvironment and immunogenicity under different MSI statuses was performed. Compared with CRC patients with MSS/MSI-L tumors, those with MSI-H tumors significantly benefited from ICI treatment. MSI-H CRC had more immune cell infiltration, higher expression of immune-related genes, and higher immunogenicity than MSS/MSI-L CRC. The MANTIS score, which is used to predict the MSI status, was positively correlated with immune cells, immune-related genes, and immunogenicity. In addition, subtype analysis showed that COAD and READ might have different immune microenvironments. MSI-H CRC may have an inflammatory tumor microenvironment and increased sensitivity to ICIs. Unlike those of MSI-H READ, the immune characteristics of MSI-H COAD may be consistent with those of MSI-H CRC.
Chips of commercial pure titanium (ASTM Grade 2) were consolidated into fully dense bulk material by severe plastic deformation (in the form of multi-pass equal channel angular pressing). The ...strengthening effect (as contributed by microstructure characteristics) was quantitatively analyzed by electron backscatter diffraction and mechanical tests. The effects of grain parameters (e.g., grain size and grain orientation) on yield strength and the Vickers micro-hardness were analyzed by the Hall–Petch relationship. The tensile curve of the consolidated sample was modeled by the Ludwik–Hollomon equation. The strain-hardening of the consolidated titanium was analyzed by the Taylor formula and the Kocks–Mecking equation. The theoretical analysis is consistent with the experimental results obtained from microstructure characterization and mechanical testing.
Summary
A new deaminase, TadA8e, was recently evolved in the laboratory. TadA8e catalyzes DNA deamination over 1,000 times faster than ABE7.10. We developed a high‐efficiency adenine base editor, ...rABE8e (rice ABE8e), combining monomeric TadA8e, bis‐bpNLS and codon optimization. rABE8e had substantially increased editing efficiencies at NG‐protospacer adjacent motif (PAM) and NGG‐PAM target sequences compared with ABEmax. For most targets, rABE8e exhibited nearly 100% editing efficiency and high homozygous substitution rates in the specific editing window, especially at Positions A5 and A6. The ability to rapidly generate plant materials with homozygous base substitutions will benefit gene function research and precision molecular breeding.
The high‐efficiency adenine base editor rABE8e combines monomeric TadA8e, bis‐bpNLS and codon optimization. rABE8e exhibited close to 100% editing efficiency and high homozygous substitution rates. With the advent of rABE8e, it is now easy to obtain homozygous substitution rice materials in the T0 generation.
Niobium nitride (NbN) is widely used in the production of superconducting nanowire single-photon detectors (SNSPDs) due to its high superconducting transition temperature and suitable energy gap. The ...processing parameters used for the preparation of NbN films and the subsequent processing of nanowires have a significant effect on the performance of the SNSPD. In this review, we will present various thin film growth methods, including magnetron sputtering, atomic layer deposition (ALD), and chemical vapor deposition (CVD). The relationships between the superconducting performance of each thin film and the corresponding deposition process will be discussed. Subsequently, NbN nanowire fabrication methods and microstructures based on thin film etching will be summarized, and their impact on the qualities of the finished SNSPDs will be systematically analyzed. Finally, we will provide an outlook for the future development of preparation for SNSPD.
Immunotherapy has been incorporated into the first- and second-line treatment strategies for non-small cell lung cancer (NSCLC), profoundly ushering in a new treatment landscape. However, both ...adaptive signaling and oncogenic (epidermal growth factor receptor (EGFR)-driven) signaling may induce PD-L1 upregulation in NSCLC. Nevertheless, the superiority of immune checkpoint inhibitors (ICIs) in advanced EGFR-mutant NSCLC is only moderate. ICIs appear to be well tolerated, but clinical activity for some advanced EGFR-mutant NSCLC patients has only been observed in a small proportion of trials. Hence, there are still several open questions about PD-L1 axis inhibitors in patients with NSCLC whose tumors harbor EGFR mutations, such as the effect of EGFR tyrosine kinase inhibitors (TKIs) or EGFR mutations in the tumor microenvironment (TME). Finding the answers to these questions requires ongoing trials and preclinical studies to identify the mechanisms explaining this possible increased susceptibility and to identify prognostic molecular and clinical markers that may predict benefits with PD-1 axis inhibition in this specific NSCLC subpopulation. The presence of multiple mechanisms, including dynamic immune TME profiles, changes in PD-L1 expression and low tumor mutational burdens, may explain the conflicting data regarding the correlation between PD-L1 axis inhibitors and EGFR mutation status. We conducted a review of this currently controversial topic in an attempt to aid in the decision-making process.
Cyclin dependent kinase inhibitor 2A (CDKN2A) is an essential regulator of immune cell functionality, but the mechanisms whereby it drives immune infiltration in hepatocellular carcinoma (HCC) remain ...unclear. In the present study, we studied the association with CDKN2A expression and immune invasion with the risk of developing HCC. A totally of 2207 different genes were found between HCC and adjacent liver tissues from TCGA and GEO databases. CDKN2A was highly expressed in HCC and associated with poorer overall survival and disease-free survival. Notably, CDKN2A expression was positively correlated with infiltrating levels into purity, B cell, CD+8 T cell, CD+4 T cell, macrophage, neutrophil, and dendritic cells in HCC. CDKN2A expression showed strong correlations between diverse immune marker sets in HCC. These findings suggest that CDKN2A expression potentially contributes to regulation of tumor-associated macrophages and can be used as a prognostic biomarker for determining prognosis and immune infiltration in HCC.
Ion adsorption-type rare earth element (REE) ore deposits in South China are a major source of heavy rare earth elements (HREE) around the world, which are of considerable economic and strategic ...significance. In these ores, REE is enriched in the clay minerals, specifically kaolinite and halloysite, which are derived from their parent granitoid by the weathering process. However, the mechanisms of supergene REE mineralization remain unclear. We investigated the nature and origin of supergene REE mineralization, based on a nanoscale study of a typical REE-mineralized granite regolith profile (ΣREEmax = 1201 ppm) in the Dazhou super-large, ion adsorption-type REE deposit, Guangxi Province, South China. Bulk mineralogical and geochemical analyses, coupled with novel nano-characterization techniques i.e., hollow fiber flow field-flow fractionation inductively coupled plasma-mass spectrometry (HF5-ICP-MS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), were used to determine the nature of the nano-minerals and nanoparticles in the regolith samples. X-ray diffraction and SEM-EDS analyses revealed that ion-adsorption clay minerals are dominated by platy-shaped kaolinite and rod-like halloysite (10 and 7 Å) within the regolith. The average clay mineral contents decreased from 38 to 15% from the fully weathered horizon to the semi-weathered horizon, whereas the proportion of halloysite increased in the clay mineral fraction in the deep horizons. The REE-bearing nanoparticles consist predominantly of macromolecules of organic matter (2-5 nm) and clay minerals (5-40 and 40-80 nm) according to the HF5-ICP-MS analysis. There is a close association between REE and Al contents in particles with sizes of 5-40 nm in the semi-weathered horizons and 40-80 nm in the highly weathered horizons, which indicates that nanoscale clay minerals (halloysite and kaolinite, respectively) are important REE carriers. In addition, nanoscale secondary REE mineral phases, including oxide, silicate, and phosphate, were identified by the SEM and TEM observations. These phases are typically adsorbed onto the surfaces of clay minerals, specifically rod-like halloysite, but have different occurrences in the regolith profile. Cesium-oxide (cerianite) and Ce-silicate (cerite) occur mainly in the upper horizon of the regolith profile, whereas low-crystallinity REE phosphates rhabdophane-(La) occur mainly in the lower horizon of the profile. Our results indicate that nano-minerals and nanoparticles affect REE enrichment and fractionation during granite weathering. Migration and accumulation of REE-bearing nano-minerals were caused by leaching and neoformation of REE-bearing nano-minerals during secondary precipitation. These processes contribute to the formation of supergene REE mineralization in granite regolith.
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