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Heat shock protein 90 (HSP90) is important for many organisms, including plants. Based on the whole genome information, the gene number, gene structure, evolutionary relationship, protein structure, and active site of the HSP90 gene family in Rosa chinensis and Rubus idaeus were determined, and the expression of the HSP90 gene under salt, and drought stresses in two rose varieties Wangxifeng and Sweet Avalanche were analyzed. Six and eight HSP90 genes were identified from R. chinensis and Ru. idaeus, respectively. Phylogenetic analysis revealed that the analyzed genes were divided into two Groups and four subgroups (Classes 1a, 1b, 2a, and 2b). Although members within the same classes displayed highly similar gene structures, while the gene structures and conserved domains of Group 1 (Class 1a and 1b) and the Group 2 (Class 2a and 2b) are different. Tandem and segmental duplication genes were found in Ru. idaeus, but not in R. chinensis, perhaps explaining the difference in HSP90 gene quantity in the two analyzed species. Analysis of cis-acting elements revealed abundant abiotic stress, photolight-response, and hormone-response elements in R. chinensis HSP90s. qRT-PCR analysis suggested that RcHSP90-1-1, RcHSP90-5-1 and RcHSP90-6-1 in Sweet Avalanche and Wangxifeng varieties played important regulatory roles under salt and drought stress. The analysis of protein structure and active sites indicate that the potential different roles of RcHSP90-1-1, RcHSP90-5-1, and RcHSP90-6-1 in salt and drought stresses may come from the differences of corresponding protein structures and activation sites. These data will provide information for the breeding of rose varieties with high stress resistance. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04052-0.
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Background: Compliance to sublingual immunotherapy (SLIT) is generally low, resulting in reduced short- and long-term clinical efficacy. Compliance is a critical factor determining the success of allergic rhinitis (AR) treatment. Objective: To analyze the compliance of patients with house dust mite (HDM)-induced AR to SLIT and the impact of coronavirus disease 2019 (COVID-19) on compliance. Methods: The clinical data of 3117 patients with HDM-induced AR who started SLIT between July 2018 and April 2022 were retrospectively reviewed. We assessed the reasons for non-compliance and the changes in non-compliance during the COVID-19 pandemic compared to the pre-pandemic period. Results: Of 3117 patients, 507 (16.27%) patients (ages, 5-67 years) were identified as non-compliant. The most common reason for non-compliance was poor efficacy (27.22%). The non-compliance rate was highest during 24-36 months of SLIT (28.13%, 153/544), followed by 12-24 months (7.02%, 91/1296). Non-compliance was significantly higher in adolescents/adults than in children (P = 0.000). Although the generalized linear model analysis indicated that compliance was affected by the COVID-19 pandemic during 3-6 months of SLIT, the overall compliance to SLIT was not significantly affected by the pandemic, according to the Kaplan-Meier survival analysis. Conclusions: The non-compliance rate of SLIT in this study was low, and poor efficacy was the most common reason for non-compliance. The compliance of adolescents/adults was lower than that of children. The COVID-19 pandemic did not significantly impact compliance to SLIT, which is an appropriate strategy for the home treatment of AR patients during major public health events.
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Paclitaxel and its derivates are the first-line chemotherapeutic agents of breast cancer, which also showed tremendous clinical value in many other diseases including ovarian cancer, lung cancer etc. However, there are many drawbacks for almost all paclitaxel or its derivates, including extremely short half-life, poor solubility and adverse events, which significantly limits their clinical applications. In this work, we designed and constructed a bispecific hydrolysis PAP-SS-PTX (term as PDC), consisting with pro-apoptosis peptide (PAP) and paclitaxel (PTX) that were conjugated together via disulfide and ester bonds. On the one hand, PAP could improve the solubility of PTX and promote cellular uptake for drugs. On the other hand, it was able to prolong the PTX half-life. We performed series of chemo-dynamical assays and showed that PDC would release active drug molecules under micro-acidic and reduction circumstance. The further assays elucidated that PDC could interrupt DNA synthesis and arrest cell division through downregulating CDK4/6 and Histone methylation that inhibit tumor growth inâ vitro. What's more, it could not only inhibit 4T1 breast tumor growth, but also prolong the survival time of mice and exert antitumor efficacy inâ vivo. It may provide a new research idea for cancer therapies via controlled release strategy in tumor microenvironment.
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The human papillomavirus (HPV) is threatening human health as it spreads globally in varying degrees. On the other hand, the speed and scope of information transmission continues to increase, as well as the significant increase in the number of HPV-related news reports, it has never been more important to explore the role of media news coverage in the spread and control of the virus. Using a decreasing factor that captures the impact of media on the actions of people, this paper develops a model that characterizes the dynamics of HPV transmission with media impact, vaccination and recovery. We obtain global stability of equilibrium points employing geometric method, and further yield effective methods to contain the HPV pandemic by sensitivity analysis. With the center manifold theory, we show that there is a forward bifurcation when R0=1. Our study suggested that, besides controlling contact between infected and susceptible populations and improving effective vaccine coverage, a better intervention would be to strengthen media coverage. In addition, we demonstrated that contact rate and the effect of media coverage result in multiple epidemics of infection when certain conditions are met, implying that interventions need to be tailored to specific situations.
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Virus del Papiloma Humano , Medios de Comunicación de Masas , Infecciones por Papillomavirus , Humanos , Medios de Comunicación de Masas/estadística & datos numéricos , Modelos Biológicos , Infecciones por Papillomavirus/transmisión , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/epidemiología , Vacunas contra Papillomavirus/administración & dosificaciónRESUMEN
Congenital heart disease (CHD) is a type of major defect that occurs during embryonic development. Although significant advances have been made in the treatment of CHD, its etiology and molecular mechanism remain unclear. To identify the critical role of SUMOylation in cardiac development, we generated SENP3 knockout mice and showed that SENP3 knockout mice die on embryonic day 8.5 with an open neural tube and reversed left-right cardiac asymmetry. Moreover, SENP3 knockout promoted apoptosis and senescence of H9C2 cells. Further studies showed that Nodal, a critical gene that forms left-right asymmetry, is regulated by SENP3 and that SENP3 regulates cell apoptosis and senescence in a Nodal-dependent manner. Furthermore, Nodal was hyper-SUMOylated after SENP3 knockout, and SUMOylation of Nodal inhibited its ubiquitination and ubiquitin-proteasome degradation pathway. Nodal overexpression enhanced cell apoptosis and senescence; however, the mutation at the SUMOylation site of Nodal reversed its effect on the apoptosis and senescence of H9C2 cells. More importantly, the SENP3-Nodal axis regulates cell senescence by inducing cell autophagy. These results suggest that the SENP3-Nodal signaling axis regulates cardiac senescence-autophagy homeostasis, which in turn affects cardiac development and results in the occurrence of CHD.
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Apoptosis , Cisteína Endopeptidasas , Proteína Nodal , Transducción de Señal , Sumoilación , Animales , Cisteína Endopeptidasas/metabolismo , Cisteína Endopeptidasas/genética , Ratones , Apoptosis/genética , Proteína Nodal/metabolismo , Proteína Nodal/genética , Corazón/embriología , Ratones Noqueados , Autofagia/genética , Senescencia Celular/genética , Línea CelularRESUMEN
Volatile organic compounds (VOCs) originating from diverse sources with complex compositions pose threats to both environmental safety and human health. Photocatalytic treatment of VOCs has garnered attention due to its high efficacy at room temperature. However, the intricate photochemical reaction generates ozone (O3), causing secondary pollution. Herein, our work developed a novel "synergistic effect" system for photocatalytic co-treatment of VOCs and O3 secondary pollution. Under the optimized reactor conditions simulated with computational fluid dynamics (CFD), MgO-loaded g-C3N4 composites (MgO/g-C3N4) were synthesized as efficient catalysts for the photocatalytic synergistic treatment process. Density functional theory (DFT) calculations, characterization, and electron paramagnetic resonance (EPR) tests revealed that the addition of MgO reduced the band gap of g-C3N4, and increased O3 molecule adsorption in the composites, efficiently harnessing the synergistic effect of O3 to generate a significant quantity of reactive oxygen radicals, thereby facilitating the removal of VOCs and O3. This study provides new insights for simultaneous elimination of VOCs and O3 secondary pollution by a photocatalytic process.
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Endothelial-mesenchymal transition (EndoMT) is a complex biological process in which endothelial cells are transformed into mesenchymal cells, and dysregulated EndoMT causes a variety of pathological processes. Transforming growth factor beta (TGF-ß) signaling effectively induces the EndoMT process in endothelial cells, and Smad2 is the critical protein of the TGF-ß signaling pathway. However, whether small ubiquitin-like modifier modification (SUMOylation) is involved in EndoMT remains unclear. Here, we show that Smad2 is predominantly modified by SUMO1 at two major SUMOylation sites with PIAS2α as the primary E3 ligase, whereas SENP1 (sentrin/SUMO-specific protease 1) mediates the deSUMOylation of Smad2. In addition, we identified that SUMOylation significantly enhances the transcriptional activity and protein stability of Smad2, regulating the expression of downstream target genes. SUMOylation increases the phosphorylation of Smad2 and the formation of the Smad2-Smad4 complex, thus promoting the nuclear translocation of Smad2. Ultimately, the wildtype, but not SUMOylation site mutant Smad2 facilitated the EndoMT process. More importantly, TGF-ß enhances the nuclear translocation of Smad2 by enhancing its SUMOylation and promoting the EndoMT process. These results demonstrate that SUMOylation of Smad2 plays a critical role in the TGF-ß-mediated EndoMT process, providing a new theoretical basis for the treatment and potential drug targets of EndoMT-related clinical diseases.
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In many nations, efforts to prevent and control COVID-19 have been significantly impeded by the SARS-CoV-2 virus ongoing mutation. The Omicron strain, a more recent and prevalent strain, has had more significant detrimental effects in countries worldwide. To investigate the impact of the Omicron BA.2 strain on vaccine efficacy, we proposed a model with vaccination and immunological decline in this research. Then, we fitted our model based on the number of daily new instances reported by the government in Jilin and Shanghai, China. We estimated the effective reproduction number Re = 4.71 for the Jilin and Re = 3.32 for Shanghai. Additionally, we do sensitivity analysis to identify the critical factors affecting the effective reproduction number Re. It was found that vaccination rate, effectiveness rate, and declining rate had a significant effect on Re. Further, we investigate the relevant parameter thresholds that make Re lower than unity. Finally, rich numerical experiments were then carried out. We observed that even when vaccine efficiency was not high, increasing vaccination rates had a significant effect on early disease transmission, that limiting social distance was the most economical and rational measure to control the spread of disease, and that for a short period, reducing immune decline was not significant in curbing disease transmission.
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COVID-19 , Vacunas , Humanos , COVID-19/prevención & control , SARS-CoV-2 , China/epidemiología , Número Básico de ReproducciónRESUMEN
Adjuvants are crucial components of vaccines that can enhance and modulate antigen-specific immune responses. Herein, we reported for the first time that human metallothionein-3 (MT3), a low molecular weight cysteine-rich metal-binding protein, was a novel promising adjuvant candidate that could help protein antigens to induce rapid, effective, and durable antigen-specific immune responses. In the present study, MT3 was fused to outer membrane protein 19 (Omp19) of Brucella abortus (MT3-Omp19, MO) and C fragment heavy chain (Hc) of tetanus neurotoxin (MT3-Hc, MH), respectively. The results showed that MT3 as a built-in adjuvant increased the Omp19- or Hc-specific antibody responses by 100-1000 folds in seven days after primary immunization. Compared to other commercially available adjuvants, MT3 could stimulate earlier (4 days after primary injection) and stronger (10-100 folds) antibody response with lower antigen dose, and its adjuvanticity relied on fusion to antigen. Although the mechanism was not clear yet, the fusion protein MO was observed to directly activate DCs, promote germinal center formation and improve the speed of Ig class switching. Interestingly, our subsequent study found that other members of the mammalian MT family (human MT1 or murine MT3 for examples) also had potential adjuvant effects, but their effects were lower than human MT3. Overall, this study explored a new function of human MT3 as a novel built-in adjuvant, which may have important clinical application potential in vaccine development against global pandemics.
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Antígenos VIH , Metalotioneína 3 , Animales , Ratones , Humanos , Adyuvantes Inmunológicos , Brucella abortus , Adyuvantes Farmacéuticos , Inmunidad Adaptativa , MamíferosRESUMEN
Background: Genetic variants in GARP (also known as LRRC32) have been reported to have significant associations with asthma and eczema in special populations, but little is known about allergic rhinitis. This study purposes to evaluate the association of single nucleotide polymorphisms (SNPs) in GARP with house dust mite (HDM)-sensitized persistent allergic rhinitis (PER) in a population of Han Chinese. Methods: In this hospital-based case-control study, 534 HDM-sensitized PER patients and 451 healthy controls were recruited from East China. In this population, six SNPs in GARP were identified. Serum total and specific IgE levels were measured with ImmunoCAP. Secondary structure and minimum free energy were predicted by RNAfold. Results: rs79525962 was associated with the risk of HDM-sensitized PER (P < 0.05). The individuals with CT+TT genotype demonstrated a higher risk of HDM-sensitized PER than those with CC genotype (adjusted ORâ=â1.393, 95% CIâ=â1.019-1.904). The homozygous genotype CC of rs3781699 rendered a lower risk of HDM-sensitized PER than the wild-type genotype AA (adjusted ORâ=â0.646, 95% CIâ=â0.427-0.976); however, the genotype and allele frequencies of rs3781699 demonstrated no associations with HDM-sensitized PER (P > 0.05). rs79525962 increased the risk of HDM-sensitized PER in the subgroup aged ≥16 years (adjusted ORâ=â1.745, 95% CIâ=â1.103-2.760), and this high risk was also found in the females (adjusted ORâ=â1.708, 95% CIâ=â1.021-2.856). The G-C haplotype of rs1320646-rs3781699 rendered a lower risk of HDM-sensitized PER than the common haplotype G-A (adjusted ORâ=â0.819, 95% CIâ=â0.676-0.993). The secondary structure of GARP altered in response to different genotypes of rs79525962 and rs3781699. Conclusion: SNP rs79525962 in the GARP gene marks a risk locus of HDM-sensitized PER in Chinese Hans.
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The primary root is the first organ to perceive the stress signals for abiotic stress. In this study, maize plants subjected to drought, heat and combined stresses displayed a significantly reduced primary root length. Metabolic and transcriptional analyses detected 72 and 5,469 differentially expressed metabolites and genes in response to stress conditions, respectively. The functional annotation of differentially expressed metabolites and genes indicated that primary root development was mediated by pathways involving phenylalanine metabolism, hormone metabolism and signaling under stress conditions. Furthermore, we found that the concentration of salicylic acid and two precursors, shikimic acid and phenylalanine, showed rapid negative accumulation after all three stresses. The expression levels of some key genes involved in salicylic acid metabolism and signal transduction were differentially expressed under stress conditions. This study extends our understanding of the mechanism of primary root responses to abiotic stress tolerance in maize.
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Sequías , Zea mays , Regulación de la Expresión Génica de las Plantas , Respuesta al Choque Térmico , Fenilalanina/genética , Fenilalanina/metabolismo , Ácido Salicílico/metabolismo , Estrés Fisiológico/genética , Zea mays/metabolismoRESUMEN
Background: Allergic rhinitis (AR) is a nasal inflammatory disease resulting from a complex interplay between genetic and environmental factors. The association between Toll-like receptor (TLR) signaling pathway and environmental factors in AR pathogenesis remains to be explored. This study aims to assess the genetic association of AR with single nucleotide polymorphisms (SNPs) in TLR signaling pathway, and investigate the roles of gene-gene and gene-environment interactions in AR. Methods: A total of 452 AR patients and 495 healthy controls from eastern China were enrolled in this hospital-based case-control study. We evaluated putatively functional genetic polymorphisms in TLR2, TLR4 and CD14 genes for their association with susceptibility to AR and related clinical phenotypes. Interactions between environmental factors (such as traffic pollution, residence, pet keeping) and polymorphisms with AR were examined using logistic regression. Models were stratified by genotype and interaction terms, and tested for the significance of gene-gene and gene-environment interactions. Results: In the single-locus analysis, two SNPs in CD14, rs2563298 (A/C) and rs2569191 (C/T) were associated with a significantly decreased risk of AR. Compared with the GG genotype, the GT and GT/TT genotypes of TLR2 rs7656411 (G/T) were associated with a significantly increased risk of AR. Gene-gene interactions (eg, TLR2 rs7656411, TLR4 rs1927914, and CD14 rs2563298) was associated with AR. Gene-environment interactions (eg, TLR4 or CD14 polymorphisms and certain environmental exposures) were found in AR cases, but they were not significant after Bonferroni correction. Conclusion: The genetic polymorphisms of TLR2 and CD14 and gene-gene interactions in TLR signaling pathway were associated with susceptibility to AR in this Han Chinese population. However, the present results were limited to support the association between gene-environment interactions and AR.
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CD147, a glycosylated transmembrane protein in the immunoglobulin superfamily, is overexpressed on the surfaces of various tumor cells and promotes cancer cell proliferation, invasion, and metastasis. Nanobodies, characterized by small sizes, high affinities and specificities, and low immunogenicities, are promising diagnostic and therapeutic tools. However, there are few reports on nanobodies that specifically target CD147. In this work, a specific anti-CD147 nanobody has been successfully identified using phage display technology. The tumor target and antitumor effects have also been detected in different CD147-positive tumors in in vitro and in vivo assays, respectively. Meanwhile, it has a synergistic effect for inhibiting 4T1-bearing mice through conjugating doxorubicin. It may afford new strategies for cancer therapies.
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Neoplasias , Anticuerpos de Dominio Único , Animales , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Ratones , Ratones Desnudos , Neoplasias/tratamiento farmacológico , Anticuerpos de Dominio Único/uso terapéutico , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: House dust mite (HDM)-induced allergic rhinitis (AR) is a highly prevalent disease with bothersome symptoms. Genetic variants of the Hippo pathway genes play a critical role in the respiratory disease. However, no study has reported associations between variants of the Hippo pathway genes and HDM-induced AR risk. METHODS: Forty-three key genes in the Hippo pathway were selected from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome pathway database, and previous reported studies. A case-control study of 222 cases and 237 controls was performed to assess the associations between 121 genetic variants in these genes and HDM-induced AR risk. DNeasy Blood & Tissues Kits were used for extracting genomic DNA from the venous blood and Infinium Asian Screening Array BeadChips for performing genotyping. A logistic regression model was applied to evaluate the effects of variants on HDM-induced AR risk. The false discovery rate (FDR) method was utilized to correct for multiple testing. The receiver operating characteristic (ROC) curve was plotted to obtain the cut-off value of total IgE for the diagnosis of HDM-induced AR. Histone modification and transcription factor binding sites were visualized by UCSC genome browser. Moreover, expression qualitative trait loci (eQTL) analysis was obtained from Genotype-Tissue Expression (GTEx) database. RESULTS: We found that rs754466 in DLG5 was significantly associated with a decreased HDM-induced AR risk after FDR correction (adjusted odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.36-0.74, p = 3.25 × 10-4 , PFDR = 3.93 × 10-2 ). The rs754466 A allele reduced the risk of HDM-induced AR in the subgroup of moderate/severe total nasal symptom score (TNSS). Furthermore, rs754466 was associated with a high mRNA expression of DLG5. Additionally, histone modification and transcription factor binding sites were rich in the region containing rs754466. CONCLUSION: Our findings indicated that rs754466 in DLG5 decreased the susceptibility to HDM-induced AR.
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BACKGROUND: Circular RNAs (circRNAs) are involved in inflammation; however, their role in allergic rhinitis (AR) remains unclear. In this study, we analyzed circRNA expression and identified a circRNA-miRNA-mRNA network through which circRNAs regulate AR pathogenesis. METHODS: We analyzed circRNA, miRNA, and mRNA expression profiles in the nasal mucosa by high-throughput sequencing (HTS), using a fold-change >1.5 and p-value < 0.05 to pinpoint significantly differentially expressed (DE) circRNAs, miRNAs, and mRNAs in AR. A DEcircRNA-DEmiRNA-DEmRNA crosstalk network was then constructed using bioinformatics and statistical analysis. Gene ontology and Kyoto encyclopedia of genes and genomes pathway analyses were performed to identify the biological terms enriched in the network; whereas RT-PCR and Sanger sequencing were used to confirm the circRNAs. RESULTS: A total of 264 DEcircRNAs were identified by HTS, including 120 upregulated and 144 downregulated in AR compared to controls. A DEcircRNA-DEmiRNA-DEmRNA crosstalk network was constructed with 17 miRNAs, 11 circRNAs, 29 mRNAs, and 64 interaction pairs. These genes were involved in the Wnt signaling pathway, TNF biosynthesis, inflammatory responses, the PI3K-Akt signaling pathway, and Toll-like receptors. Of the 11 DEcircRNAs, hsa_circ_0008668 and circTRIQK were upregulated, whereas hsa_circ_0029853 and circRNA_01002 were downregulated in AR tissues. Sanger sequencing confirmed the back-splicing junctions of these circRNAs. CONCLUSIONS: We constructed a novel DEcircRNA-DEmiRNA-DEmRNA network for AR that provides a basis for future studies to investigate its underlying molecular mechanisms.
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Host defense systems can invade viral infection through immune responses and cellular metabolism. Recently, many studies have shown that cellular metabolism can be reprogrammed through N6 -methyladenosine (m6 A) modifications during viral infection. Among of them, methyltransferase like-14 enzyme (METTL14) plays an important role in m6 A RNA modification, yet its antiviral function still remains unclear. In this work, it is uncovered that metal-protein nanoparticles designated GSTP1-MT3(Fe2+ ) (MPNP) can polarize macrophages toward the M1 phenotype and activate immune responses to induce Interferon-beta (IFN-ß) production in vesicular stomatitis virus (VSV)-infected macrophages. Further investigation elucidates that a high dose of IFN-ß can promote the expression of METTL14, which has a well anti-VSV capacity. Moreover, it is found that other negative-sense single-stranded RNA viruses, such as influenza viruses (H1N1(WSN)), can also be inhibited through either immune responses or METTL14. Collectively, these findings provide insights into the antiviral function of METTL14 and suggest that the manipulation of METTL14 may be a potential strategy to intervene with other negative-sense single-stranded RNA viruses infections.
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Antivirales/farmacología , Inmunidad Innata/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A , Nanopartículas del Metal/química , Nanocompuestos/química , Animales , Línea Celular , Expresión Génica/efectos de los fármacos , Células HEK293 , Humanos , Interferón beta/genética , Hierro/química , Metiltransferasas/metabolismo , Ratones , Nanopartículas , Fenotipo , Células RAW 264.7 , Células THP-1 , Virus de la Estomatitis Vesicular Indiana/metabolismo , Vesiculovirus , Replicación Viral/efectos de los fármacosRESUMEN
BACKGROUND: The polymorphisms inside microRNA target sites locating in the 3'-UTR region may introduce the micro-RNA-binding changes, which may regulate the gene expression and correlate with the potential diseases. OBJECTIVES: We aimed to investigate whether the polymorphisms in microRNA target sites of transforming growth factor beta (TGF-ß) signaling pathway genes are associated with the susceptibility of mite-sensitized allergic rhinitis (AR) in a Han Chinese population. METHODS: In this case-control study, 454 AR patients and 448 healthy controls were recruited. Three HapMap single-nucleotide polymorphisms (SNPs) were mapped to putative microRNA recognition sites and genotyped by TaqMan allelic discrimination assay. RESULTS: The genotype and allele frequencies of 3 SNPs (rs1590 in TGFBR1; rs1434536 and rs17023107 in BMPR1B) showed lack of significant association with AR. However, in the subgroup analysis, the TG, GG, and TG/GG genotypes of rs1590 exhibited significantly increased risk of AR in the male subgroup (TG: adjusted OR = 1.57, 95% CI = 1.08-2.31; GG: adjusted OR = 1.76, 95% CI = 1.09-2.86; TG/GG: adjusted OR = 1.62, 95% CI = 1.13-2.33). The CT genotypes of rs17023107 might have potential to protect against AR in the patients age of <15 years (adjusted OR = 0.37, 95% CI = 0.14-0.95) and the males (adjusted OR = 0.48, 95% CI = 0.25-0.95). No significant association was found between SNPs and the total serum IgE level. CONCLUSIONS: In a Han Chinese population, stratified by age and gender, susceptibility to mite-sensitized AR may be associated with 2 SNPs (rs1590 and rs17023107) in microRNA target sites of TGF-ß signaling pathway genes.
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Regiones no Traducidas 3' , MicroARNs/genética , Polimorfismo de Nucleótido Simple , Rinitis Alérgica/etiología , Rinitis Alérgica/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo , Adolescente , Adulto , Alelos , Biomarcadores , Niño , Susceptibilidad a Enfermedades , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Masculino , Rinitis Alérgica/diagnóstico , Adulto JovenRESUMEN
The effect of the layer sequence on the ballistic performance of Ti6Al4V (35 mm)/CP-Ti (5 mm) laminated composite armor, against a 12.7 mm armor piercing projectile, was systematically investigated, both experimentally and computationally. By introducing the Johnson-Cook constitutive model and fracture criterion, the penetrating process of the composite plate was well-simulated. Furthermore, the influence of the layer sequence on the ballistic performance and failure mechanism of the composite plate was evaluated from the perspective of energy absorption and the stress distribution. Numerical simulation results of the macro morphology and penetration depth agreed well with the experimental results. The results showed that the energy absorption histories of each layer and stress distribution of the composite plate were found to be significantly affected by the arrangement sequence. The ballistic performance of Ti6Al4V/CP-Ti was far superior to that of CP-Ti/Ti6Al4V because more energy was absorbed in the early stage of the penetration process, thereby reducing the damage to the rear face. Further studies showed that the first principal stress in both structures was radially distributed in space, but was mainly concentrated at the rear face when the CP-Ti was placed at the front. Therefore, this stress induced cracking and failure in that region and, consequently, lowered the overall ballistic performance.
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In this work, a near ß-type Ti5.1Al2.5Cr0.5Fe4.5Mo1.1Sn1.8Zr2.9Zn alloy was hot-rolled at the temperature of 800-880 °C with a thickness reduction of 87.5% and then heat-treated with the strategy of 880 °C/1 h/air cooling (AC) + 650 °C/3 h/AC. The microstructure difference between the hot-rolled and heat-treated titanium alloys and its influence on the ballistic impact behavior of the hot-rolled and heat-treated titanium alloys were analyzed. The microstructural investigation revealed that the average size of the acicular secondary α phase (αs) dropped from 75 to 42 nm, and the corresponding amount of this phase increased significantly after heat treatment. In addition, the dislocation density of the α and ß phases decreased from 0.3340 × 1015/m2 and 4.6746 × 1015/m2 for the hot-rolled titanium alloy plate to 0.2806 × 1015/m2 and 1.8050 × 1015/m2 for the heat-treated one, respectively. The high strength of the heat-treated titanium alloy was maintained, owing to the positive contribution of the acicular secondary α phase. Furthermore, the critical fracture strain increased sharply from 19.9% for the hot-rolled titanium alloy plate to 23.1% for the heat-treated one, thereby overcoming (to some extent) the constraint of the strength-ductility trade-off. This is mainly attributed to the fact that the dislocation density and the difference between the dislocation densities of the α and ß phases decreased substantially, and deformation localization was effectively suppressed after heat treatment. Damage to the hot-rolled and heat-treated titanium alloy plates after the penetration of a 7.62 mm ordinary steel core projectile at a distance of 100 m was assessed via industrial computer tomography and microstructure observation. The results revealed that a large crack (volume: 2.55 mm3) occurred on the rear face and propagated toward the interior of the hot-rolled titanium alloy plate. The crack tip was connected to a long adiabatic shear band with a depth of 3 mm along the thickness direction. However, good integrity of the heat-treated titanium alloy plate was maintained, owing to its excellent deformation capability. Ultimately, the failure mechanism of the hot-rolled and heat-treated titanium alloy plates was revealed by determining the crack-forming reasons in these materials.
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BACKGROUND: Polymorphism -509C/T in the promoter of transforming growth factor beta1 (TGFB1) gene is implicated in the pathogenesis of asthma. This polymorphism might also act to regulate the development of allergic rhinitis (AR). OBJECTIVES: To investigate whether -509C/T is associated with AR susceptibility and severity in a Han Chinese population. METHODS: The study enrolled 263 patients with persistent AR and 249 healthy controls. AR patients were classified as mild or moderate/severe AR groups according to the Allergic Rhinitis and its Impact on Asthma classification. TGFB1 gene polymorphism -509C/T was genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum total Immunoglobulin E (IgE) and specific IgE levels were determined using an ImmunoCAP. RESULTS: Significant difference was found in the allele frequency of TGFB1 -509C/T between AR patients and healthy controls (P = .027) but not in the genotype frequency (P =.051). However, the genotype frequency of TGFB1 -509C/T showed significant difference between the mild AR group, the moderate/severe AR group, and the control group (P = .012); between the moderate/severe AR group and the control group (P =.036); between the mild AR group and the moderate/severe AR group (P = .038); but not between the mild AR group and the control group (P =.075). CONCLUSION: TGFB1 promoter polymorphism -509C/T may be associated with the susceptibility and the severity of persistent AR of Han Chinese, but the functional relationship still needs clarification.