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Summary: Current studies on the immune microenvironment of colorectal cancer (CRC) were mostly limited to the tissue level, lacking relevant studies in the peripheral blood, and failed to describe its alterations in the whole process of adenocarcinoma formation, especially of adenoma carcinogenesis. Here, we constructed a large-scale population cohort and used the CyTOF to explore the changes of various immune cell subsets in peripheral blood of CRC. We found monocytes and basophils cells were significantly higher in adenocarcinoma patients. Compared with early-stage CRC, effector CD4+T cells and naive B cells were higher in patients with lymph node metastasis, whereas the basophils were lower. We also performed random forest algorithm and found monocytes play the key role in carcinogenesis. Our study draws a peripheral blood immune cell landscape of the occurrence and development of CRC at the single-cell level and provides a reference for other researchers.

Enzyme-production microorganisms typically occupy a dominant position in composting, where cellulolytic microorganisms actively engage in the breakdown of lignocellulose. Exploring strains with high yields of cellulose-degrading enzymes holds substantial significance for the industrial production of related enzymes and the advancement of clean bioenergy. This study was inclined to screen cellulolytic bacteria, conduct genome analysis, mine cellulase-related genes, and optimize cellulase production. The potential carboxymethylcellulose-hydrolyzing bacterial strain Z2.6 was isolated from the maturation phase of pig manure-based compost with algae residuals as the feedstock and identified as Bacillus velezensis. In the draft genome of strain Z2.6, 31 related cellulolytic genes were annotated by the CAZy database, and further validation by cloning documented the existence of an endo-1,4-β-D-glucanase (EC 3.2.1.4) belonging to the GH5 family and a β-glucosidase (EC 3.2.1.21) belonging to the GH1 family, which are predominant types of cellulases. Through the exploration of ten factors in fermentation medium with Plackett–Burman and Box–Behnken design methodologies, maximum cellulase activity was predicted to reach 2.98 U/mL theoretically. The optimal conditions achieving this response were determined as 1.09% CMC-Na, 2.30% salinity, and 1.23% tryptone. Validation under these specified conditions yielded a cellulose activity of 3.02 U/mL, demonstrating a 3.43-fold degree of optimization. In conclusion, this comprehensive study underscored the significant capabilities of strain Z2.6 in lignocellulolytic saccharification and its potentialities for future in-depth exploration in biomass conversion.

Hafnia (HfO2) is a potential candidate for the high-k gate dielectrics in next-generation high-power electronics. Its thermal transport properties, which determine the performance of these related high-power electronics, are critical while rarely investigated. Here, the thermal transport properties of HfO2 in a wide temperature range of 300–2000 K with a phase transition between monoclinic and tetragonal phases at ∼1765 K, are systematically studied based on the temperature-dependent effective potential landscapes with both propagating and coherence thermal transport considered. It is found that the cage-like structure of monoclinic HfO2 results in the avoid crossing in the phonon band structures, which increases the three-phonon scattering largely. Some phonon modes with significant scattering matrix can have relatively larger 3ph and 4ph scattering rates in tetragonal HfO2. Consequently, the thermal conductivity of HfO2 is only 11.95–1.72 W/mK at 300–2000 K. Our results further show that propagating phonon channels dominate the thermal transport in HfO2 and contribute at least 70% to the total thermal conductivity. The rest of the thermal conductivity of HfO2 results from the coherence thermal transport channels, which is caused by the overlap of phonons. Four-phonon scatterings are found to be significant for the thermal transport in tetragonal HfO2, which can result in a thermal conductivity reduction of ∼50%. Our results here advance the understanding of the thermal transport in HfO2, which may benefit the performance optimization of HfO2-related electronics. [ABSTRACT FROM AUTHOR]

Abstract Objectives Gliomas with comutations of isocitrate dehydrogenase (IDH) genes and telomerase reverse transcriptase (TERT) gene promoter (IDHmut pTERTmut) show distinct biological features and respond to first‐line treatment differently in comparison with other gliomas. This study aimed to characterize the IDHmut pTERTmut gliomas in multimodal MRI using the radiomic method and establish a precise diagnostic model identifying this group of gliomas. Methods A total of 140 patients with untreated primary gliomas were admitted between 2016 and 2020 to West China Hospital as a discovery cohort, including 22 IDHmut pTERTmut patients. Thirty‐four additional cases from a different hospital were included in the study as an independent validation cohort. A total of 3654 radiomic features were extracted from the preoperative multimodal MRI images (T1c, FLAIR, and ADC maps) and filtered in a data‐driven approach. The discovery cohort was split into training and test sets by a 4:1 ratio. A diagnostic model (multilayer perceptron classifier) for detecting the IDHmut pTERTmut gliomas was trained using an automatic machine‐learning algorithm named tree‐based pipeline optimization tool (TPOT). The most critical radiomic features in the model were identified and visualized. Results The model achieved an area under the receiver‐operating curve (AUROC) of 0.971 (95% CI, 0.902–1.000), the sensitivity of 0.833 (95% CI, 0.333–1.000), and the specificity of 0.966 (95% CI, 0.931–1.000) in the test set. The area under the precision‐recall curve (AUCPR) was 0.754 (95% CI, 0.572–0.833) and the F1 score was 0.833 (95% CI, 0.500–1.000). In the independent validation set, the model reached 0.952 AUROC, 0.714 sensitivity, 0.963 specificity, 0.841 AUCPR, and 0.769 F1 score. MR radiomic features of the IDHmut pTERTmut gliomas represented homogenous low‐complexity texture in three modalities. Conclusions An accurate diagnostic model was constructed for detecting IDHmut pTERTmut gliomas using multimodal radiomic features. The most important features were associated with the homogenous simple texture of IDHmut pTERTmut gliomas in MRI images transformed using Laplacian of Gaussian and wavelet filters.

Abstract Colorectal cancer (CRC) is a major malignancy threatening the health of people in China and screening could be effective for preventing the occurrence and reducing the mortality of CRC. We conducted a multicenter, prospective clinical study which recruited 4,245 high‐risk CRC individuals defined as having positive risk‐adapted scores or fecal immunochemical test (FIT) results, to evaluate the clinical performance of the multitarget fecal immunochemical and stool DNA (FIT‐sDNA) test for CRC screening. Each participant was asked to provide a stool sample prior to bowel preparation, and FIT‐sDNA test and FIT were performed independently of colonoscopy. We found that 186 (4.4%) were confirmed to have CRC, and 375 (8.8%) had advanced precancerous neoplasia among the high CRC risk individuals. The sensitivity of detecting CRC for FIT‐sDNA test was 91.9% (95% CI, 86.8–95.3), compared with 62.4% (95% CI, 54.9–69.3) for FIT (P

Abstract Background Obg-like ATPase 1 (OLA1) is a highly conserved GTPase, which was over expressed in a variety of malignant tumors, but its role in colorectal cancer (CRC) was poorly studied. Patients and methods Three public CRC gene databases were applied for OLA1 mRNA expression detection. The clinical data of 111 CRC patients were retrospectively collected from the Second Affiliated Hospital of Zhejiang University (SAHZU) for OLA1 protein expression and Kaplan-Meier Survival analysis. OLA1 stably knocked out CRC cell lines were conducted by CRISPR-Cas9 for experiments in vitro and in vivo. Results OLA1 was highly expressed in 84% CRC compared to matched surrounding tissues. Patients with OLA1 high expression had a significantly lower 5-year survival rate (47%) than those with OLA1 low expression (75%). OLA1 high expression was an independent factor of poor prognosis in CRC patients. OLA1-KO CRC cell lines showed lower ability of growth and tumorigenesis in vitro and in vivo. By mRNA sequence analysis, we found 113 differential express genes in OLA1-KO cell lines, of which 63 were hypoxic related. HIF1α was a key molecule in hypoxic regulation. Further molecular mechanisms showed HIF1α /CA9 mRNA and/or protein levels were heavily downregulated in OLA1-KO cell lines, which could explain the impaired tumorigenesis. According to previous studies, HIF1α was a downstream gene of GSK3β, we verified GSK3β was over-activated in OLA1-KO cell lines. Conclusion OLA1 was a new gene that was associated with carcinogenesis and poor outcomes in CRC by activation of HIF1α/CA9 axis, which may be interpreted by GSK3β.

Transition metal phosphides (TMPs) and phosphates (TM‐Pis) nanostructures are promising functional materials for energy storage and conversion. Nonetheless, controllable synthesis of crystalline/amorphous heterogeneous TMPs/TM‐Pis nanohybrids or related nanoarchitectures remains challenging, and their electrocatalytic applications toward overall water splitting (OWS) are not fully explored. Herein, the Ni2P nanocrystals anchored on amorphous V‐Pi nanosheet based porous flower‐like nanohybrid architectures that are self‐supported on carbon cloth (CC) substrate (Ni2P/V‐Pi/CC) are fabricated by conformal oxidation and phosphorization of pre‐synthesized NiV‐LDH/CC. Due to the unique microstructures and strong synergistic effects of crystalline Ni2P and amorphous V‐Pi components, the obtained Ni2P/V‐Pi/CC owns abundant active sites, suitable surface/interface electronic structure and optimized adsorption‐desorption of reaction intermediates, resulting in outstanding electrocatalytic performances toward hydrogen and oxygen evolution reactions in alkaline media. Correspondingly, the assembled Ni2P/V‐Pi/CC||Ni2P/V‐Pi/CC electrolyzer only needs an ultralow cell voltage (1.44 V) to deliver 10 mA cm−2 water‐splitting currents, exceeding its counterparts, recently reported bifunctional catalysts‐based devices, and Pt/C/CC||IrO2/CC pairs. Moreover, the Ni2P/V‐Pi/CC||Ni2P/V‐Pi/CC manifests remarkable stability. Also, such device shows a certain prospect for OWS in acidic media. This work may spur the development of TMPs/TMPis‐based nanohybrid architectures by combining structure and phase engineering, and push their applications in OWS or other clean energy options. [ABSTRACT FROM AUTHOR]