Pulmonary fibrosis (PF) is one of the leading causes of death in systemic sclerosis (SSc) patients. Although all SSc patients are characterized by autoimmunity, only part of them suffer from PF, ...suggesting that beside autoimmunity, some additional factors are involved in the initiation of PF in SSc. In this study, we aimed to identify genetic polymorphisms associated with the status of PF in SSc. We performed that an exhaustive search of the PubMed database was performed to identify eligible studies. Then, a comprehensive meta-analysis was performed by comparing PF
+
-SSc and PF
−
-SSc patients to identify genetic polymorphisms associated with the status of PF in SSc. Among eight SSc-associated susceptibility polymorphisms which were applied for meta-analysis,
IRF5
rs2004640 polymorphism (OR 1.12; 95% CI 1.02–1.22,
P
= 1.39 × 10
−2
),
STAT4
rs7574865 polymorphism (OR 1.25; 95% CI 1.07–1.47,
P
= 5.3 × 10
−3
),
IRAK1
rs1059702 polymorphism (OR 1.20; 95% CI 1.05–1.37,
P
= 0.007), and
CTGF
G-945C polymorphism (OR 1.42; 95% CI 1.18–1.71,
P
= 0.002) are associated with PF status in SSc, while
TNFAIP3
rs5029939,
CD226
rs763361,
CD247
rs2056626, and
IRF5
rs10488631 polymorphisms are not. Since IRF5, STAT4, and IRAK1 are important regulatory factors in the control of innate immune responses and CTGF is involved in the synthesis of extracellular matrix, these results suggest a role of the innate immunity and matrix compounds in the pathogenesis of PF in SSc.
KRAS-mutant lung adenocarcinomas (LUADs) are heterogeneous and frequently occur in smokers. The heterogeneity of KRAS-mutant LUAD has been an obstacle for the drug discovery.
We integrated ...multiplatform datatypes and identified two corresponding subtypes in the patients and cell lines. We further characterized the features of these two subtypes and performed drug screening to identify subtype-specific drugs. Finally, we used the defining features of the KRAS subtypes for drug sensitivity prediction.
Patient-Subtype 1 (PS1) was characterized by increased smoking-related mutational signature activity, a low tumor-infiltrating lymphocyte (TIL)-associating score and STK11/KEAP1 co-mutations. Patient-Subtype 2 (PS2) was characterized by an increased smoking-related methylation signature activity, a high TIL-associating score and increased KRAS dependency. The cell line subtypes faithfully recapitulated all the patients' features. Drug screening of the two cell line subtypes yielded several potential candidates, such as cytarabine and enzastaurin for Cell-line-Subtype 1 (CS1) and a BTK inhibitor QL-XII-61 for Cell-line-Subtype 2 (CS2). The defining features, such as smoking-related methylation signature, were significantly associated with the sensitivity to several drugs.
The heterogeneity of KRAS-mutant LUAD is associated with smoking-related genomic and epigenomic aberration along with other features such as immunogenicity, KRAS dependency and STK11/KEAP1 co-mutations. These features might be used as biomarkers for drug sensitivity prediction.
This research was funded by the Young Scientists Fund of the National Natural Science Foundation of China, the Natural Science Foundation of Fujian Province, China and the Education and Research Foundation for Young Scholars of Education Department of Fujian Province, China.
To control the morphology and particle size of dense spherical molybdenum powder prepared by radio frequency（RF） plasma from irregular molybdenum powder as a precursor, plasma process parameters were ...optimized in this paper. The effects of the carrier gas flow rate and molybdenum powder feeding rate on the shape and size of the final products were studied. The molybdenum powder morphology was examined using high-resolution scanning electron microscopy. The powder phases were analyzed by X-ray diffraction. The tap density and apparent density of the molybdenum powder were investigated using a Hall flow meter and a Scott volumeter. The optimal process parameters for the spherical molybdenum powder preparation are 50 g/min powder feeding rate and 0.6 m^3/h carrier gas rate. In addition, pure spherical molybdenum powder can be obtained from irregular powder, and the tap density is enhanced after plasma processing. The average size is reduced from 72 to 62 μm, and the tap density is increased from 2.7 to 6.2 g/cm^3. Therefore, RF plasma is a promising method for the preparation of high-density and high-purity spherical powders.
Background: KRAS-mutant lung adenocarcinomas (LUADs) are heterogeneous and frequently occur in smokers. The heterogeneity of KRAS-mutant LUAD has been an obstacle for the drug discovery. Methods: We ...integrated multiplatform datatypes and identified two corresponding subtypes in the patients and cell lines. We further characterized the features of these two subtypes and performed drug screening to identify subtype-specific drugs. Finally, we used the defining features of the KRAS subtypes for drug sensitivity prediction. Findings: Patient-Subtype 1 (PS1) was characterized by increased smoking-related mutational signature activity, a low tumor-infiltrating lymphocyte (TIL)-associating score and STK11/KEAP1 co-mutations. Patient-Subtype 2 (PS2) was characterized by an increased smoking-related methylation signature activity, a high TIL-associating score and increased KRAS dependency. The cell line subtypes faithfully recapitulated all the patients' features. Drug screening of the two cell line subtypes yielded several potential candidates, such as cytarabine and enzastaurin for Cell-line-Subtype 1 (CS1) and a BTK inhibitor QL-XII-61 for Cell-line-Subtype 2 (CS2). The defining features, such as smoking-related methylation signature, were significantly associated with the sensitivity to several drugs. Interpretation: The heterogeneity of KRAS-mutant LUAD is associated with smoking-related genomic and epigenomic aberration along with other features such as immunogenicity, KRAS dependency and STK11/KEAP1 co-mutations. These features might be used as biomarkers for drug sensitivity prediction. Fund: This research was funded by the Young Scientists Fund of the National Natural Science Foundation of China, the Natural Science Foundation of Fujian Province, China and the Education and Research Foundation for Young Scholars of Education Department of Fujian Province, China. Keywords: KRAS-mutant lung adenocarcinoma, KRAS subtypes, TIL-associating score, Smoking-related methylation signature, Smoking-related mutational signature, Drug sensitivity prediction
•Different interfaces between Pt and TmIG are designed by grown on different oriented substrates.•Only Pt/TmIG/(1 1 1)GGG sample showed square AHE while Pt/110TmIG exhibits nonhysterisis AHE ...loop.•Square AHE loops are resulted from the interfacial Tm3+ ions moment.•Our results provide a way to detect the rare earth moment switching in iron garnets by the electrical measurements.
We performed anomalous Hall effect (AHE) measurements in Pt/Tm3Fe5O12 (Pt/TmIG) bilayers grown on (1 1 0) and (1 1 1)-oriented Gd3Ga5O12 (GGG) substrates (Pt/110TmIG and Pt/111TmIG). Qualitative differences were observed in the two sets of samples: at low magnetic fields only Pt/111TmIG displays square AHE loop, while Pt/110TmIG exhibits non-hysteretic AHE behavior. Systematic temperature-dependent AHE measurements in Pt/111TmIG showed double switching events of AHE loops below 30 K, which was attributed to the larger moment of Tm3+ sublattice at low temperatures and was consistent with earlier theoretical calculations A. Lehmann-Szweykowska et al., Phys. Rev. B 37, 459 (1988). Our results confirmed the strong coupling of Tm3+ magnetic moment with the lattice and the crucial role of the interfacial structure, suggesting a way to detect rare earth moment switching in iron garnets by electrical measurements.
Antiferromagnets have shown great potential for replacing ferromagnets in spintronics applications in recent years. In this work, antiferromagnetic La0.35Sr0.65MnO3 (AFM-LSMO) thin films were grown ...on ultrathin ferromagnetic La0.7Sr0.3MnO3 (FM-LSMO) layer over a wide temperature range. The different AFM-LSMO growth temperatures introduced variation of strain states in the AFM-LSMO layer, changing the AFM-LSMO magnetic properties. Considering the thermally activated switching model of antiferromagnetic grains, the behaviour of AFM-LSMO growth temperature-dependent exchange bias effect are explained. This work demonstrates the modulation of exchange bias effect through the control of AFM-LSMO growth conditions, suggesting possibility to control and probe oxide antiferromagnets via exchange bias coupling.
•Exchange bias in antiferromagnetic La0.35Sr0.65MnO3/ferromagnetic La0.7Sr0.3MnO3 bilayers was investigated.•Higher antiferromagnet growth temperature induced larger tensile strain, affecting the magnetic properties of bilayers.•Antiferromagnet growth temperature greatly affected the microstructures, and hence blocking temperature, of the bilayers.
The SmBi4Fe0.5Co0.5Ti3O15 compounds were prepared by the insertion of the SmFe0.5Co0.5O3 into the Bi4Ti3O12 host and the conventional solid state reaction method, respectively. X-ray diffraction ...analysis indicates that the conventional solid state reaction method favors the formation of a single phase four-layer Aurivillius phase of SmBi4Fe0.5Co0.5Ti3O15 more easily than that prepared by the insertion method. Magnetic and ferroelectric measurements demonstrate that the samples prepared by both methods exhibit coexistence of strong ferromagnetic and weak ferroelectric behaviors at room temperature. Compared with the Bi5FeTi3O15, the ferromagnetism of the SmBi4Fe0.5Co0.5Ti3O15 was dramatically enhanced by the partial substitution of Co for Fe and Sm for Bi. The SmBi4Fe0.5Co0.5Ti3O15 samples exhibit large magnetic responses (2M r~643 memu/g and coercive fields 2H c~344 Oe) at room temperature.
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