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Abstract Background Modulation of the immune system is one of the principal roles of Vitamin D, for which the effects are exerted via the vitamin D receptor (VDR). Importantly, variants in the VDR gene have been susceptible in the past to raise the risk of asthma in several populations. These effects of VDR allelic markers remain speculative in the Chinese Han population. Results A case-control study of 1090 individuals including 567 asthmatic patients was realized on five SNPs within the VDR gene. Only rs7975232 (ApaI) marker showed a significant association with asthma (P = 0.009). Haplotype analysis of the five VDR polymorphisms showed a significant association with asthma (global-p value = 0.012). Conclusion Although the susceptibility of VDR gene variants with asthma could not be confirmed for all SNPs tested in this study, the significant association obtained for rs7975232 provides evidence for a previously unknown report about the Chinese Han population and may raise the susceptibility of VDR to be a candidate gene for asthma.

Abstract Background Mutation in SPINK5 causes Netherton syndrome, a rare recessive skin disease that is accompanied by severe atopic manifestations including atopic dermatitis, allergic rhinitis, asthma, high serum IgE and hypereosinophilia. Recently, single nucleotide polymorphism (SNP) of the SPINK5 was shown to be significantly associated with atopy, atopic dermatitis, asthma, and total serum IgE. In order to determine the role of the SPINK5 in the development of asthma, a case-control study including 669 asthma patients and 711 healthy controls in Han Chinese was conducted. Methods Using PCR-RFLP assay, we genotyped one promoter SNP, -206G>A, and four nonsynonymous SNPs, 1103A>G (Asn368Ser), 1156G>A (Asp386Asn), 1258G>A (Glu420Lys), and 2475G>T (Glu825Asp). Also, we analyzed the functional significance of -206G>A using the luciferase reporter assay and electrophoresis mobility shift assay. Results we found that the G allele at SNP -206G>A was associated with increased asthma susceptibility in our study population (p = 0.002, odds ratio 1.34, 95% confidence interval 1.11–1.60). There was no significant association between any of four nonsynonymous SNPs and asthma. The A allele at -206G>A has a significantly higher transcriptional activity than the G allele. Electrophoresis mobility shift assay also showed a significantly higher binding efficiency of nuclear protein to the A allele compared with the G allele. Conclusion Our findings indicate that the -206G>A polymorphism in the SPINK5 is associated with asthma susceptibility in a Chinese Han population.

Background: Mesenchymal to epithelial transition factor (MET) dysregulation in non-small-cell-lung-cancer (NSCLC) is understudied, with scant data on treatment outcomes. Methods: We retrospectively examined 160 NSCLC patients: 125 with primary MET mutations (further classified into MET exon 14 (METex14) skipping mutations and primary MET amplifications) and 35 with secondary MET amplifications. Patients underwent varied treatments: Chemotherapy, Immune monotherapy, Crizotinib, or Savolitinib. Secondary MET amplification patients were grouped by treatment: Group A (Class Ib MET-TKI with third-generation EGFR-TKI), Group B (Crizotinib with first-generation EGFR-TKI), and Group C (Crizotinib alone). One hundred and thirty patients have completed the whole treatment process. Their data were included in the study's survival analysis (included 95 patients with primary MET mutations and 35 patients with secondary MET amplifications). Results: Among METex14 skipping mutations patients (n = 57), median progression free survival (PFS) was: Chemotherapy 7.64 m, Crizotinib 8.5 m, Savolitinib 9.3 m, and Immunotherapy 3.87 m. Targeted therapies and chemotherapy significantly outperformed Immunotherapy. Sub-group analysis indicated splice donor region mutations benefited more than those at the polypyrimidine tract (9.23 m vs. 4.03 m, P = 0.038). For primary MET amplifications (n = 38), PFS was: Chemotherapy 2.84 m, Crizotinib 3.80 m, Savolitinib 5.23 m, and Immunotherapy 3.30 m. Patients with copy number (CN) > 5 had longer PFS than CN ≤ 5 (5.17 m vs. 3.44 m, P = 0.039). In secondary MET amplifications (n = 35), Group A and B had similar PFS (6.77 m and 6.57 m) versus Group C (3.13 m). Dual-target therapy PFS showed no difference between CN ≤ 5 and CN > 5 (8.63 m vs. 6.27 m, P = 0.29). Conclusion: NSCLC patients with METex14 skipping mutations benefit more from targeted therapies, especially those with splice donor mutations. MET amplification patients benefit universally from targeted therapies; primary MET amplifications show higher benefits with increased copy numbers. For secondary MET amplifications post-EGFR-TKI resistance, dual-target therapy surpasses Crizotinib monotherapy, independent of MET copy number. [ABSTRACT FROM AUTHOR]

The acoustic, velocity, and surface pressure fields of vertical jet impingement are studied utilizing pressure sensors, particle image velocimetry, and pressure sensitive paint measurements in parallel. Experiments are carried out at Mach numbers of 1.1 and 1.2, with corresponding Reynolds number of 5.8 × 10 5 and 6.2 × 10 5 , respectively. The focus is placed on the understanding of the relationships between noise generation mechanisms within these fields. Features of fluctuation and pulsation of velocity and surface pressure are analyzed using proper orthogonal decomposition and Fourier transformation. Different types of acoustic tones are found corresponding to unique patterns in the decomposition of velocity and pressure fields. Large-scale coherent structures in the velocity field and monopoles in the surface pressure field are correlated with pure tones due to the shedding of coherent structures. Corresponding velocity fluctuations can be detected throughout the jet, reflecting the global effect of aeroacoustic resonance. Near-plate coherent flow structures and dipoles of surface pressure pulsation are associated with impingement tones. These structures account for a smaller portion of the total kinetic energy and act as a local effect near the plate. Additionally, broadband noise is presented as quadrupoles of surface pressure pulsation. The dominant modes of surface pressure exhibit morphological similarity and consistent spectral characteristics with the acoustic poles in the Lighthill analogy. [ABSTRACT FROM AUTHOR]

Leaf morphology plays a crucial role in plant classification and provides a significant model for studying plant diversity while directly impacting photosynthetic efficiency. In the case of melons, leaf shape not only influences production and classification but also represents a key genetic trait that requires further exploration. In this study, we utilized forward genetics to pinpoint a recessive locus, dubbed Cmrl (Round leaf), which is responsible for regulating melon leaf shape. Through bulked segregant analysis sequencing and extensive evaluation of a two-year F2 population, we successfully mapped the Cmrl locus to a 537.07 kb region on chromosome 8 of the melon genome. Subsequent genetic fine-mapping efforts, leveraging a larger F2 population encompassing 1322 plants and incorporating F2:3 phenotypic data, further refined the locus to an 80.27 kb interval housing five candidate genes. Promoter analysis and coding sequence cloning confirmed that one of these candidates, MELO3C019152.2 (Cmppr encoding a pentatricopeptide repeat-containing family protein, Cmppr), stands out as a strong candidate gene for the Cmrl locus. Notably, comparisons of Cmrl expressions across various stages of leaf development and different leaf regions suggest a pivotal role of Cmrl in the morphogenesis of melon leaves. [ABSTRACT FROM AUTHOR]

The mechanical properties of various Ti-6Al-4V alloys are influenced by their respective microstructures. This study generated an ultrafine-grain (UFG) Ti-6Al-4V alloy featuring bimodal grain distribution characteristics achieved through initial heat treatment, multi-axial forging (MF), and annealing. The study also extensively examined the evolution process of the alloy's microstructure. By subjecting the materials to heat treatments at 900 °C with air cooling and 950 °C with air cooling, both materials were found to be consisted of primary α (αp) and transformed β (αs+β) regions with different proportions. Following MF, the sample treated at 900 °C displays a microstructure featuring UFGs of α+β surrounding larger micron-sized αp grains. On the other hand, the sample treated at 950 °C displays a microstructure distinguished by twisted αs lamellar and fragmented β grains surrounding larger micron-sized αp grains. Following annealing, no significant grain growth was observed in the sample. The geometrically necessary dislocations (GNDs) within the UFGs were eliminated, though some GNDs persisted within the αp grains. The samples undergoing the 900 °C heat treatment, MF, and subsequent annealing exhibited elevated strength (1280 MPa) and total elongation (10.7%). This investigation introduces a novel method for designing the microstructure of the Ti-6Al-4V alloy to achieve superior performance. [ABSTRACT FROM AUTHOR]

[Objective] This study comprehensively evaluated the drought tolerance of watermelon resources by screening drought tolerant germplasm resources and identifying key drought tolerance indexes at seedling stage to provide support for drought tolerance breeding of watermelon. [Method] Twenty-five watermelon materials were selected for two treatments of drought stress and normal watering in pots at seedling stage. Seven growth indexes including plant height, root length, aboveground fresh weight, underground fresh weight, aboveground dry weight, underground dry weight and root-shoot ratio, and six physiological indexes including chlorophyll content, soluble protein content, proline content, nialondialdehyde con-tent, catalase activity and relative conductivity were measured. Using the methods of membership function, multiple linear regression analysis and cluster analysis, the response differences of watermelon gerniplasm to drought stress were compared, the drought resistance of gerniplasm at seedling stage was evaluated, and the key drought resistance indexes were screened. [Result] Drought stress inhibited the growth and development of watermelon seedlings. Drought stress significantly inhibited shoot fresh mass and root fresh mass of watermelon seedlings, generally reduced plant height, root length, shoot dry mass and root dry mass, and had positive and negative effects on root-shoot ratio. After drought treatment, proline content in watermelon leaves increased significantly, catalase activity increased generally, soluble protein content and relative conductivity in leaves decreased generally, while chlorophyll and nialondialdehyde contents showed differences among germplasms. [Conclusion] The watermelon materials with strong drought resistance at seedling stage including M20, ZTC, M33, M24 and M26, and they can be used for further breeding watermelon resources with drought resistance. Shoot fresh weight, catalase activity, soluble protein content, pro-line content, underground dry weight, and root length could be used as the traits for evaluating drought resistance of watermelon seedlings. [ABSTRACT FROM AUTHOR]