Immunohistochemical p16 expression in the prognosis of patients with sinonasal squamous cell carcinoma.

In sinonasal squamous cell carcinoma (SNSCC), the prognostic relevance of p16INK4a (p16) expression has been reported rarely. This study aims to examine the immunohistochemical expression of p16 and investigate the possibility of p16 as a prognostic factor for SNSCC. The medical records of 173 individuals with SNSCC between 2010 and 2022 were retrospectively reviewed. The researchers examined patients' demographics, p16 status, staging, tumor histological subtypes, treatment details, recurrence, metastasis, and survival outcomes. p16 was found in 22.0% (38/173) of SNSCC patients, and there was no difference between inverted papilloma-SNSCC (19.6%) and de novo SNSCC (23.0%). p16 status did not correlate with all the cases' age, gender, clinical stage, or therapy features. p16-positive patients had a considerably superior 5-year overall survival (OS) rate (80.7% vs. 57.5%, p=0.039) and a slight tendency in progression-free survival (PFS) rate (68.1% vs. 52.0%, p=0.15), except in stage T4b cases. In maxillary sinus lesions, p16-positive SNSCC had a better 5-year OS (87.4% vs. 49.2%, p=0.03) rate and PFS (79.1% vs. 40.7%, p=0.01) rate than p16-negative SNSCC. Among patients without skull base involvement (82.9% vs. 57.7%, p=0.037) or orbital invasion (86.9% vs. 57.3%, p=0.02), p16-positive SNSCC confers benefits in OS rates more than p16-negative SNSCC. Immunohistochemical p16 expression may be a predictive predictor in individuals with maxillary sinus SCC, non-T4b stage, without skull base involvement, and without orbital invasion.

Household mold exposure interacts with inflammation-related genetic variants on childhood asthma: a case-control study.

BACKGROUND: A number of studies have examined the association between mold exposure and childhood asthma. However, the conclusions were inconsistent, which might be partly attributable to the lack of consideration of gene function, especially the key genes affecting the pathogenesis of childhood asthma. Research on the interactions between genes and mold exposure on childhood asthma is still very limited. We therefore examined whether there is an interaction between inflammation-related genes and mold exposure on childhood asthma. METHODS: A case-control study with 645 asthmatic children and 910 non-asthmatic children aged 3-12 years old was conducted. Eight single nucleotide polymorphisms (SNPs) in inflammation-related genes were genotyped using MassARRAY assay. Mold exposure was defined as self-reported visible mold on the walls. Associations between visible mold exposure, SNPs and childhood asthma were evaluated using logistic regression models. In addition, crossover analyses were used to estimate the gene-environment interactions on childhood asthma on an additive scale. RESULTS: After excluding children without information on visible mold exposure or SNPs, 608 asthmatic and 839 non-asthmatic children were included in the analyses. Visible mold exposure was reported in 151 asthmatic (24.8%) and 119 non-asthmatic children (14.2%) (aOR 2.19, 95% CI 1.62-2.97). The rs7216389 SNP in gasdermin B gene (GSDMB) increased the risk of childhood asthma with each C to T substitution in a dose-dependent pattern (additive model, aOR 1.32, 95% CI 1.11-1.57). Children carrying the rs7216389 T allele and exposed to visible mold dramatically increased the risk of childhood asthma (aOR 3.21; 95% CI 1.77-5.99). The attributable proportion due to the interaction (AP: 0.47, 95% CI 0.03-0.90) and the relative excess risk due to the interaction (RERI: 1.49, 95% CI 0-2.99) were statistically significant. CONCLUSIONS: In the present study, there was a significant additive interaction between visible mold exposure and rs7216389 SNP on childhood asthma. Future studies need to consider the gene-environment interactions when exploring the risk factors of childhood asthma.

Interaction between antibiotic use and MS4A2 gene polymorphism on childhood eczema: a prospective birth cohort study.

BACKGROUND: Eczema is usually the first allergic manifestation to appear in life attributed to gene-environment interactions. IL13, IL4, MS4A2 and ILR4A are four key inflammatory genes associated with atopy. This study aimed to explore gene-environment interactions on eczema in early life among the above four genes and environmental factors in Chinese Han children. METHODS: Five hundred ninety-seven children from a birth cohort who completed two-year follow-up were enrolled and their cord blood was collected. Subjects were genotyped for six polymorphisms in the aforementioned four genes. The children were followed at 6, 12 and 24 months, with epidemiologic information and medical history of eczema collected by questionnaire and eczema assessed by dermatologists. RESULTS: Among the 597 children, 168 were diagnosed with eczema and the others were not after 2 years of follow-up. MS4A2 rs569108 GG genotype (P = 1.68E-02, odds ratio (OR) = 4.66) and antibiotic use (P = 3.75E-4, OR = 2.02) were found independently associated with development of childhood eczema. Children with both antibiotic use and MS4A2 rs569108 GG genotype were more likely to develop eczema than those with only antibiotic use or GG homozygote (OR = 6.24 VS. 2.04 or 4.68). CONCLUSIONS: MS4A2 rs569108 polymorphism and antibiotic use were solely associated with eczema, and they interacted with each other to increase the risk of developing the disease in Chinese Han toddlers. Long-term follow-up along with functional and replication studies are still needed.

CCNB1 may as a biomarker for the adipogenic differentiation of adipose-derived stem cells in the postoperative fat transplantation of breast cancer.

Background: Adipose-derived stem cells (ADSCs) are closely associated with the survival rate of transplanted fat in breast reconstruction after breast cancer surgery. Nevertheless, the intrinsic mechanisms regulating ADSCs adipogenic differentiation remain ambiguous. The aim of our study was to explore the relevant genes and pathways to elucidate the potential mechanisms of adipogenic differentiation in ADSCs. Methods: The Gene Expression Omnibus (GEO) dataset GSE61302 was downloaded and analyzed to identify differentially expressed genes (DEGs). Key genes and signaling pathways were obtained through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional and enrichment analysis. Protein-protein interaction (PPI) network and hub gene analyses were performed with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Cytoscape software. Finally, the transcription levels of hub genes in the adipogenic differentiated group and undifferentiated group of ADSCs were compared via real-time quantitative polymerase chain reaction (RT-qPCR). Results: In total, 1,091 DEGs were identified through bioinformatics analysis of the adipogenic differentiated group and undifferentiated group. If was then found that the 10 downregulated key genes, CCNB1, NUSAP1, DLGAP5, TTK, CCNB2, KIF23, BUB1B, CDC20, CDCA8, and KIF11 may play important roles in the adipogenic differentiation of ADSCs. Subsequent in vitro experimental verification also revealed that the messenger RNA (mRNA) expression levels of cyclin B1 in adipogenic differentiated cells and undifferentiated cells were significantly different at the early stage (P<0.05), but there was no significant difference at the late stage (P>0.05). Conclusions: As a key gene, CCNB1 might be a potential biomarker in the adipogenic differentiation of ADSCs at the early stage.

Fluconazole assists berberine to kill fluconazole-resistant Candida albicans.

It was found in our previous study that berberine (BBR) and fluconazole (FLC) used concomitantly exhibited a synergism against FLC-resistant Candida albicans in vitro. The aim of the present study was to clarify how BBR and FLC worked synergistically and the underlying mechanism. Antifungal time-kill curves indicated that the synergistic effect of the two drugs was BBR dose dependent rather than FLC dose dependent. In addition, we found that BBR accumulated in C. albicans cells, especially in the nucleus, and resulted in cell cycle arrest and significant change in the transcription of cell cycle-related genes. Besides BBR, other DNA intercalators, including methylene blue, sanguinarine, and acridine orange, were all found to synergize with FLC against FLC-resistant C. albicans. Detection of intracellular BBR accumulation by fluorescence measurement showed that FLC played a role in increasing intracellular BBR concentration, probably due to its effect in disrupting the fungal cell membrane. Similar to the case with FLC, other antifungal agents acting on the cell membrane were able to synergize with BBR. Interestingly, we found that the efflux of intracellular BBR was FLC independent but strongly glucose dependent and associated with the drug efflux pump Cdr2p. These results suggest that BBR plays a major antifungal role in the synergism of FLC and BBR, while FLC plays a role in increasing the intracellular BBR concentration.

Clinical characteristics and genetic profiles of 44 patients with severe combined immunodeficiency (SCID): report from Shanghai, China (2004-2011).

Severe combined immunodeficiency (SCID), a rare type of genetic associated immune disorder, is poorly characterized in mainland China. We retrospectively reviewed 44 patients with SCID who received treatment from 2004 to 2011 in Shanghai, China, and herein summarize their clinical manifestations and immunological and preliminary genetic features. The male-to-female ratio was 10:1. Twenty five patients presented with X-SCID symptoms. Only one patient was diagnosed before the onset of symptoms due to positive family history. The mean time of delay in the diagnosis of X-SCID was 2.69 months (range, 0.5-8.67). Thirty-seven of the 44 patients died by the end of 2011 with the mean age of death being 7.87 months (range, 1.33-31). Six patients received hematopoietic stem cell transplantation (HSCT); only one of them survived, who was transplanted twice. The time between onset and death was shorter in the HSCT-treated group compared with the untreated group (2.87 ± 1.28 and 3.34 ± 0.59 months, respectively), probably due to active infections during transplantation. Bacillus Calmette-Guérin (BCG) complications occurred in 14 of the 34 patients who received BCG vaccination. Transfusion-induced graft-versus-host disease occurred in 5 patients. Total 20 mutations in interleukin-2 receptor subunit gamma (IL2RG) were identified in 22 patients, including 11 novel mutations. Most patients were misdiagnosed before referred to our SCID Center. Therefore, establishing more diagnostic centers dedicated to the care of PID and accessible by primary immunodeficiency patients will facilitate early, correct diagnosis and better care of SCID in China.

[Efficacy and safety of tulobuterol patch versus oral salbutamol sulfate in children with mild or moderate acute attack of bronchial asthma: a comparative study].

OBJECTIVE: To compare tulobuterol patch and oral salbutamol sulfate in terms of efficacy and safety in children with mild or moderate acute attack of bronchial asthma. METHODS: A total of 92 children with mild and moderate acute asthmatic attack were randomly divided into salbutamol group (n=46) and tulobuterol group (n=46). Both groups received routine treatment with antihistamine, selective leukotriene receptor antagonist and glucocorticoid. In addition, the salbutamol group was given slow-release capsules of salbutamol sulfate, and the tulobuterol group was treated with tulobuterol patch. The two groups were compared with respect to symptom scores of cough, wheeze, respiratory rate, wheezing sound, three depression sign and peak expiratory flow, as well as adverse events. RESULTS: As the treatment proceeded, symptom scores decreased in both groups; on the third day of treatment, all symptom scores except cough score showed a significant decrease in both groups (P<0.05), but the tulobuterol group had significantly lower symptom scores than the salbutamol group (P<0.05). On the fourteenth day of treatment, both groups had a significant decrease in cough score (P<0.05), but the tulobuterol group had a significantly lower cough score than the salbutamol group (P<0.05). One child developed hand trembling in the salbutamol group, while no adverse event occurred in the tulobuterol group. CONCLUSIONS: Compared with oral salbutamol sulfate, tulobuterol patch has a better therapeutic efficacy and a higher safety in children with mild or moderate acute asthmatic attack.

Clinical efficacy of tetrandrine in artificial stone-associated silicosis: A retrospective cohort study.

Background: Outbreaks of silicosis have occurred among workers in the artificial stone (AS) industry, and there is currently no effective antifibrosis treatment for silicosis. Design: A retrospective cohort study. Methods: We retrospectively analyzed the clinical data of 89 artificial stone-associated silicosis patients treated in Shanghai Pulmonary Hospital (China). Patients who agreed to be administered tetrandrine entered the observation group and those who disagreed entered the control group. Changes in chest HRCT, pulmonary function, and clinical symptoms of patients in two groups were compared pre- and post-treatment. Results: After treatment for 3-12 months, 56.5%-65.4% of patients in the observation group showed improvements in HRCT imaging, while there was no improvement in the control group (p < 0.05). Disease progression occurred in 0%-17.4% of patients in the observation group after 3-12 months of treatment compared with 44.4%-92.0% of patients in the control group (p < 0.05). After 3 months of treatment, the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and diffusing capacity of the lung for carbon monoxide (DLco) in the observation group increased by 136.7 ± 189.2 mL (p < 0.05), 124.2 ± 169.9 mL (p < 0.05), and 1.4 ± 2.3 mL/min/mmHg (p > 0.05), respectively, while those in the control group decreased (145.8 ± 356.5; 107.5 ± 272.1; 1.9 ± 3.8). After 6 months of treatment, FVC, FEV1, and DLco in the observation group increased by 207.8 ± 372.2 mL (p > 0.05), 107.8 ± 295.2 mL (p > 0.05) and 0.7 ± 6.0 mL/min/mmHg (p > 0.05), respectively, while those of the control group decreased (383.3 ± 536.7; 215.6 ± 228.9; 1.4 ± 1.7). The incidences of clinical symptoms such as cough, expectoration, dyspnea, chest tightness, and chest pain in the observation group were decreased-after treatment (all p < 0.05), while the incidences of these symptoms increased in the control group, although the change was not statistically significant (all p > 0.05). Conclusion: Tetrandrine can control and delay the progression of AS-associated silicosis fibrosis, with improved chest HRCT imaging and pulmonary function.

Genomic profiling and prognostic factors of H3 K27M-mutant spinal cord diffuse glioma.

H3 K27-altered diffuse midline glioma is a highly lethal pediatric-type tumor without efficacious treatments. Recent findings have highlighted the heterogeneity among diffuse midline gliomas with different locations and ages. Compared to tumors located in the brain stem and thalamus, the molecular and clinicopathological features of H3 K27-altered spinal cord glioma are still largely elusive, thus hindering the accurate management of patients. Here we aimed to characterize the clinicopathological and molecular features of H3 K27M-mutant spinal cord glioma in 77 consecutive cases. We found that the H3 K27M-mutant spinal cord glioma, with a median age of 35 years old, had a significantly better prognosis than H3 K27M-mutant brain tumors. We noticed a molecular heterogeneity of H3 K27M-mutant spinal cord astrocytoma via targeted sequencing with 34 cases. TP53 mutation which occurred in 58.8% of cases is mutually exclusive with PPM1D (26%) and NF1 (44%) mutations. The TP53-mutant cases had a significantly higher number of copy number variants (CNV) and a marginally higher proportion of pediatric patients (age at diagnosis <18 years old, p = 0.056). Cox regression and Kaplan-Meier curve analysis showed that the higher number of CNV events (≥3), chromosome (Chr) 9p deletion, Chr 10p deletion, ATRX mutation, CDK6 amplification, and retinoblastoma protein (RB) pathway alteration are associated with worse survival. Cox regression analysis with clinicopathological features showed that glioblastoma histological type and a high Ki-67 index (>10%) are associated with a worse prognosis. Interestingly, the histological type, an independent prognostic factor in multivariate Cox regression, can also stratify molecular features of H3 K27M-mutant spinal cord glioma, including the RB pathway, KRAS/PI3K pathway, and chromosome arms CNV. In conclusion, although all H3 K27M-mutant spinal cord diffuse glioma were diagnosed as WHO Grade 4, the histological type, molecular features representing chromatin instability, and molecular alterations associated with accelerated cell proliferative activity should not be ignored in clinical management.

Risk Factors of Silicosis Progression: A Retrospective Cohort Study in China.

Background: Silicosis poses a threat to workers' health due to the irreversible lung lesions. Design: A retrospective cohort study. Methods: A total of 259 patients [80 worked with artificial stone (AS), 179 with non-artificial stone (non-AS)] with confirmed silicosis were included in this study. Forty-one of AS and 91 of non-AS had approximately 2 years' follow-up records [lung function tests and high-resolution computer tomography (HRCT)]. Compared with the first records, increased, densified, or newly emerging lesions in lung HRCT images were judged as progression of the disease. Cox proportional hazards models were used to determine the risk factors. Kaplan-Meier survival curve and log-rank test were used to compare prognostic factors for cumulative risk of progression. Results: In 132 patients with median follow-up of 24.0 months (IQR, 13.8, 24.9), 66 patients showed progression, in them, 36 (87.8%) were from AS group and 30 (32.9%) from non-AS group. Working experience of AS processing (hazard ratio, 5.671; 95% CI, 3.048-10.550) and complicated silicosis in CT images (hazard ratio, 2.373; 95% CI, 1.379-4.082) were the main risk factors associated with progression. Forced vital capacity decreased after 1-year (241.5 vs. 55.2 mL) and 2-year (328.1 vs. 68.8 mL) follow-up in the two groups (AS vs. non-AS). History of anti-tuberculosis medication, chest oppression and pain, ground-glass opacity, pleural abnormalities, and restrictive pulmonary dysfunction were more frequently found on HRCT images in the AS group than non-AS group. Lung functions (DLCO, %) were lower in the current/former smokers than the non-smokers (P < 0.05) in AS patients. Conclusion: Prevention and protection rules are needed to be enforced in the occupation involving AS processing; smoking may be associated with declined lung function in AS patients.

[Mechanisms of Fe-cyclam/H2O2 System Catalyzing the Degradation of Rhodamine B].

Fenton reaction is a traditional method for the treatment of dye-containing wastewater. However, this process should be performed in a narrow pH range and requires large amounts of ferrous salt input, limiting its application. In this work, a robust iron complex bearing a cross-bridge cyclam ligand (Fe-cyclam) was successfully prepared. This complex could effectively activate H2O2 to degrade rhodamine B at a pH range of 2-7. The Fe-cyclam/H2O2 system was more effective in the degradation of rhodamine B than the Fenton reaction, when the input [Fe] was lower than 50 µmol·L-1. Moreover, in addition to rhodamine B, the Fe-cyclam/H2O2 system was also capable of degrading dyes such as acid red 88, acid orange II, reactive red 24, and neutral red. This system was more efficient in the degradation of azo dyes than that of triphenylmethane dyes. The removal of rhodamine B remained higher than 90% in three cycle experiments, indicating the excellent stability of Fe-cyclam. The quenching experiments proved that the degradation of rhodamine B by Fe-cyclam/H2O2 was a free-radical-control process. Meanwhile, the electron paramagnetic resonance captured the signals of high valent FeV-oxo species, indicating that FeV-oxo possibly mediated the degradation of rhodamine B in the Fe-cyclam/H2O2 system. This work proves the potential application of Fe-cyclam/H2O2 in the degradation of dyes in a practical environment.

Drug-eluting beads transarterial chemoembolization sequentially combined with radiofrequency ablation in the treatment of untreated and recurrent hepatocellular carcinoma.

BACKGROUND: Drug-eluting beads transarterial chemoem-bolization (DEB-TACE) has the advantages of slow and steady release, high local concentration, and low incidence of adverse drug reactions compared to the traditional TACE. DEB-TACE combined with sequentially ultrasound-guided radiofrequency ablation (RFA) therapy has strong anti-cancer effects and little side effects, but there are fewer related long-term studies until now. AIM: To explore the outcome of DEB-TACE sequentially combined with RFA for patients with primary hepatocellular carcinoma (HCC). METHODS: Seventy-six patients with primary HCC who underwent DEB-TACE sequentially combined with RFA were recruited. Forty patients with untreated HCC were included in Group A, and 36 patients with recurrent HCC were included in Group B. In addition, 40 patients with untreated HCC who were treated with hepatectomy were included in Group C. The serological examination, preoperative magnetic resonance imaging examination, and post-treatment computed tomography enhanced examination were performed for all patients. The efficacy was graded as complete remission (CR), partial remission (PR), stable disease and progressive disease at the 3rd, 6th, and 9th. All patients were followed up for 3 years and their overall survival (OS), disease-free survival (DFS) were assessed. RESULTS: The efficacy of Group A and Group C was similar (P > 0.05), but the alanine aminotransferase, aspartate aminotransferase and total bilirubin of Group A were lower than those of Group C (all P < 0.05). The proportions of CR (32.5%), PR (37.5%) were slightly higher than Group A (CR: 27.5%, PR: 35%), but the difference was not statistically significant (χ 2 = 0.701, P = 0.873). No operational-related deaths occurred in Group A and Group C. The OS (97.5%, 84.7%, and 66.1%) and the DFS (75.0%, 51.7%, and 35.4%) of Group A at the 1st, 2nd, and 3rd year after treatment were similar with those of Group C (OS: 90.0%, 79.7%, and 63.8%; DFS: 80.0%, 59.7%, and 48.6%; P > 0.05). The OS rates in Group A and Group B (90%, 82.3%, and 66.4%) were similar (P > 0.05). The DFS rates in Group B (50%, 31.6%, and 17.2%) were lower than that of Group A (P = 0.013). CONCLUSION: The efficacy of DEA-TACE combined with RFA for untreated HCC is similar with hepatectomy. Patients with recurrent HCC could get a longer survival time through the combined treatment.

The MKK7 inhibitor peptide GADD45ß-I attenuates ER stress-induced mitochondrial dysfunction in HT22 cells: Involvement of JNK-Wnt pathway.

JNK, a member of the mitogen activated protein kinases (MAPKs) superfamily, plays a key role in cell death in many neurological disorders, but systemic inhibition of JNK has detrimental side effects. JNK can be regulated by two direct upstream kinases: MAPK kinase 4 (MKK4) and MAPK kinase 7 (MKK7). Here, we investigated the effect of GADD45ß-I, a recently designed cell-permeable inhibitor peptide for MKK7, on endoplasmic reticulum (ER) stress-induced cytotoxicity in neuronal HT22 cells. We found that treatment with the ER stress inducer tunicamycin (TM) increased the phosphorylation of JNK and MKK7 in HT22 cells, which was nullified by GADD45ß-I. GADD45ß-I significantly attenuated TM-induced toxicity via inhibiting apoptotic cell death, as evidenced by decreased number of TUNEL-positive cells and reduced caspase-3 activity. GADD45ß-I treatment also decreased expression of ER stress associated pro-apoptotic proteins and prevented morphological changes of the ER after TM exposure. In addition, inhibition of mitochondrial oxidative stress and preservation of intracellular ATP levels were observed in GADD45ß-I-treated cells. The experiments using siRNA transfection and Topflash reporter assay revealed a possible involvement of Wnt/ß-catenin pathway in GADD45ß-I-induced protection in HT22 cells. In summary, our results demonstrated that GADD45ß-I exerted protective effects against TM-induced cytotoxicity via regulating JNK-Wnt pathway. Targeting MKK7 could represent a new therapeutic strategy for the treatment of neurological diseases where ER stress associated neuronal injury are involved.

Requirement for Ergosterol in Berberine Tolerance Underlies Synergism of Fluconazole and Berberine against Fluconazole-Resistant Candida albicans Isolates.

Candida albicans is one of the most common fungal pathogens. Our previous study demonstrated that concomitant use of berberine (BBR) and fluconazole (FLC) showed a synergistic action against FLC-resistant C. albicans in vitro and BBR had a major antifungal effect in the synergism, while FLC played a role of increasing the intracellular BBR concentration. Since the antifungal activity of BBR alone is very weak (MIC > 128 µg/mL), it was assumed that FLC-resistant C. albicans was naturally tolerant to BBR, and this tolerance could be reversed by FLC. The present study aimed to elucidate the mechanism underlying BBR tolerance in FLC-resistant C. albicans and its disruption by FLC. The ergosterol quantitative analysis showed that the BBR monotreatment could increase the content of cellular ergosterol. Real-time RT-PCR revealed a global upregulation of ergosterol synthesis genes in response to BBR exposure. In addition, exogenous ergosterol could decrease intracellular BBR concentration and increase the expression of drug efflux pump genes, further reducing the susceptibility of C. albicans to BBR. Similar to FLC, other antifungal agents acting on ergosterol were able to synergize with BBR against FLC-resistant C. albicans. However, the antifungal agents not acting on ergosterol were not synergistic with BBR. These results suggested that ergosterol was required for BBR tolerance, and FLC could enhance the susceptibility of FLC-resistant C. albicans to BBR by inhibiting ergosterol synthesis.

Drug susceptibilities of yeast cells are affected when expressing mutant Candida albicans drug resistance protein.

In the present study, wild-type and mutant Candida drug resistance protein 1 (Cdr1p) was expressed in Saccharomyces cerevisiae and phenotype alterations were observed in order to understand the importance of Cdr1p in azole resistance. Cdr1p was subjected to site-directed mutagenesis resulting in an alteration (W629L) to transmembrane segment 4 (TMS4). The susceptibilities to azole antifungal drugs of yeast cells as well as passive efflux of Rhodamine 6G were measured. The mutant strain showed greater sensitivity to azole antifungal drugs than the strain with the wild-type plasmid (AD-CDR1) as well as reduced efflux of Rhodamine 6G. Taken together, these phenotypic alterations of yeast cells were caused by the mutation in TMS4 of Cdr1p, which suggests that TMS4 plays a major role in azole antifungal drug efflux and is an azole antifungal drug-binding site.

Four-locus gene interaction between IL13, IL4, FCER1B, and ADRB2 for asthma in Chinese Han children.

RATIONALE: IL13, IL4, IL4RA, FCER1B, and ADRB2 are important inflammatory genes associated with immunoglobulin E levels. This study attempts to determine whether there are gene-gene interactions in the five genes among asthmatic children of Chinese Han nationality. METHODS: Nine single-nucleotide polymorphisms (SNPs) in the five genes were genotyped in 1,000 asthmatic children and 1,000 healthy controls using TaqMan real-time quantitative polymerase chain reaction. Multifactor-dimensionality reduction method was applied for the analysis. RESULTS: A four-way gene-gene interaction model consisting of IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108 was chosen as the optimal one for determining asthma susceptibility (testing balanced accuracy = 0.6089, cross-validation consistency = 10/10, P = 6.98E-05). Each of the four SNPs was identified to have an independent association with childhood asthma (G allele of rs20541, odds ratio (OR) = 1.24, P = 1.23E-03; T allele of rs2243250, OR = 1.25, P = 3.81E-03; A allele of rs1042713, OR = 1.29, P = 6.75E-05; G allele of rs569108, OR = 1.27, P = 3.86E-03). Individuals homozygous for the risk alleles at all the four loci (rs20541 GG, rs2243250 TT, rs1042713 AA, and rs569108 GG) had a significantly higher risk of asthma compared with those without any risk homozygotes (OR = 13.55, P = 4.28E-03), and also greater than those with less than four risk homozygotes (OR = 10.09, P = 6.51E-03). CONCLUSIONS: Our results suggest that IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108, four SNPs with significant sole effect on asthma, interact to confer a higher risk for the disease in Chinese Han children.

[Heat-responsive mechanisms in plants revealed by proteomic analysis: A review].

Heat stress is a major abiotic stress that limits plant growth and productivity. In recent years, proteomic investigations provide more information for understanding the sophisticated heat-responsive molecular mechanism in plants at systematic biological level. The heat-responsive proteomic patterns in several plants, i. e., model plants (Arabidopsis thaliana), staple food crops (soybean, rice and wheat), heat-tolerant plants (Agrostis stolonifera, Portulaca oleracea, and Carissa spinarum), grapevine, Populus euphratica, Medicago sativa, and Pinellia ternate, were reported. A total of 838 heat-responsive proteins have been identified in these studies. Among them, 534 proteins were induced and the expression of 304 proteins was reduced in plants under heat stress. In this paper, the diverse protein patterns in plants under various heat stress conditions (30-45 °C for 0-10 d) were analyzed integratively. This provided new evidences and clues for further interpreting the signaling and metabolic pathways, e.g., signaling, stress and defense, carbohydrate and energy metabolism, photosynthesis, transcription, protein synthesis and fate, membrane and transport, in heat-responsive networks, and laid a foundation for a holistic understanding of the molecular regulatory mechanism in plants in response to heat stress.

Identification of IL13 C1923T as a Single Nucleotide Polymorphism for Asthma in Children from Mauritius.

Background: Research increasingly suggests that asthma is a familial and hereditary disorder and that genetic and environmental factors play a key role in its pathogenesis. Objective: The aim of this study was to investigate the associations between 10 single nucleotide polymorphism (SNP) loci in the development of asthma in children from the Mauritian population. Methods: The study population consisted of 193 children with asthma and 189 healthy controls from the Mauritian population. Asthma was diagnosed in accordance with the American Thoracic Society criteria. TaqMan real-time quantitative polymerase chain reaction was used to detect the genotypes of the SNP loci. Results: No statistically significant differences (p>0.05) were found between the experimental and control group in genotype distribution among nine of the loci (MS4A2 E237G, MS4A2 C-109T, ADRB2 R16G, IL4RA Q551R, IL4RA I75V, IL4 C-590T, IL13 A2044G, IL13 C-1112T, and CHI3L1 C-131G). However, the frequency of IL13 C1923T TT in the asthma group was significantly higher than in the control group (odds ratio=2.119, p=0.033) suggesting that carriers of IL13 C1923T TT in the Mauritian population may have a more significant risk of developing asthma. Conclusion: The nine loci have little contribution to the development of childhood asthma in the Mauritian population. IL13 C1923T TT has been detected to be the susceptible genotype and may have a significant effect on the pathogenesis of childhood asthma in the Mauritian population.

[Genetic mapping of resistant gene to southern corn rust and the tagging analysis on different genetic background].

Southern corn rust (SCR) is a destructive disease in maize. The inbred line Qi319 is highly resistant to southern corn rust. SSR technique was employed to preliminary mapping of the resistance gene. Bulked segregant analysis revealed that two primers, phi 118 and phi 041, amplified polymorphic bands. SSR analysis on populations indicated the two primers were linked to the rust resistance gene, which was mapped on the short arm of chromosome 10. In addition, comparative analysis of the amplification bands among different populations revealed that the amplification products with the same primer in different populations were dissimilar. This result indicates that the genetic background may affect results of gene mapping and tagging. So, it is important to select suitable population to performing molecular marker analysis and gene mapping.

[Construction of expression vector with BG2 gene and its transformation in wheat].

beta-1,3-glucanase(BG2) is one of the pathogensis-related-proteins(PR). Study of these proteins and their related genes is one of the hot points in plant genetic engineering of disease resistance for a long time. In this research, specific primers were designed with the enzyme cleavage site of Spe I in its forward one and Not I site in the backward according to the BG2 gene sequence. Using this pair of primers, BG2 gene, which was contained in the plasmid of pRTL2, was amplified and confirmed by sequencing the amplified fragment inserted into T-easy vector. The positive clone containing BG2 gene was digested with the enzymes of Spe I/Not I and then BG2 gene was inserted into the Xba I/Not I sites of super expression binary vector pATC940. The reconstructed expression vector named as pATCBG2 was introduced into the wheat of Longfumai10 and Longfumai3 (Triticum aestivum L. em. Thell) through the particle gun transformation method. The Kanamysin resistant (Km') transformants were obtained. PCR, Dot-blotting and PCR-Southern hybridization analysis showed that the BG2 gene was integrated into the genome of wheat. Result of pathogen inoculation assay on the transgenic plants showed that the transgenic plants had a higher resistant disease score of 1-2 grade than the control.