Reference genome and annotation updates lead to contradictory prognostic predictions in gene expression signatures: a case study of resected stage I lung adenocarcinoma.

RNA-sequencing enables accurate and low-cost transcriptome-wide detection. However, expression estimates vary as reference genomes and gene annotations are updated, confounding existing expression-based prognostic signatures. Herein, prognostic 9-gene pair signature (GPS) was applied to 197 patients with stage I lung adenocarcinoma derived from previous and latest data from The Cancer Genome Atlas (TCGA) processed with different reference genomes and annotations. For 9-GPS, 6.6% of patients exhibited discordant risk classifications between the two TCGA versions. Similar results were observed for other prognostic signatures, including IRGPI, 15-gene and ORACLE. We found that conflicting annotations for gene length and overlap were the major cause of their discordant risk classification. Therefore, we constructed a prognostic 40-GPS based on stable genes across GENCODE v20-v30 and validated it using public data of 471 stage I samples (log-rank P < 0.0010). Risk classification was still stable in RNA-sequencing data processed with the newest GENCODE v32 versus GENCODE v20-v30. Specifically, 40-GPS could predict survival for 30 stage I samples with formalin-fixed paraffin-embedded tissues (log-rank P = 0.0177). In conclusion, this method overcomes the vulnerability of existing prognostic signatures due to reference genome and annotation updates. 40-GPS may offer individualized clinical applications due to its prognostic accuracy and classification stability.

Assessing the causal association between human blood metabolites and the risk of epilepsy.

BACKGROUND: Metabolic disturbance has been reported in patients with epilepsy. Still, the evidence about the causal role of metabolites in facilitating or preventing epilepsy is lacking. Systematically investigating the causality between blood metabolites and epilepsy would help provide novel targets for epilepsy screening and prevention. METHODS: We conducted two-sample Mendelian randomization (MR) analysis. Data for 486 human blood metabolites came from a genome-wide association study (GWAS) comprising 7824 participants. GWAS data for epilepsy were obtained from the International League Against Epilepsy (ILAE) consortium for primary analysis and the FinnGen consortium for replication and meta-analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. RESULTS: 482 out of 486 metabolites were included for MR analysis following rigorous genetic variants selection. After IVW and sensitivity analysis filtration, six metabolites with causal effects on epilepsy were identified from the ILAE consortium. Only four metabolites remained significant associations with epilepsy when combined with the FinnGen consortium [uridine: odds ratio (OR) = 2.34, 95% confidence interval (CI) = 1.48-3.71, P = 0.0003; 2-hydroxystearate: OR = 1.61, 95% CI = 1.19-2.18, P = 0.002; decanoylcarnitine: OR = 0.82, 95% CI = 0.72-0.94, P = 0.004; myo-inositol: OR = 0.77, 95% CI = 0.62-0.96, P = 0.02]. CONCLUSION: The evidence that the four metabolites mentioned above are associated with epilepsy in a causal way provides a novel insight into the underlying mechanisms of epilepsy by integrating genomics with metabolism, and has an implication for epilepsy screening and prevention.

Long-term safety and efficacy of bisphosphonate therapy in advanced lung cancer with bone metastasis.

Aim: This retrospective, observational study evaluated the long-term (>12 months) safety and effectiveness of bisphosphonate. Methods: Data collected for 359 patients included quantity and proportion of adverse events (AEs) and skeletal-related events (SREs), and times to first AE and first SRE. Results: Patients in the ≤24-month group experienced significantly fewer AEs compared with the >24-month treatment group (p = 0.008), and treatment for >24 months was a potential risk factor for AEs (p = 0.05). Neither the proportion nor the risk of SRE was significantly associated with therapy duration (p = 0.525 and 0.084, respectively). Conclusion: Bisphosphonate treatment beyond 2 years may increase the risk of AEs, but may prolong SRE-free survival early after 24 months, compared with medication administered for ≤24 months.

The survival of patients with lung cancer with bone metastases has improved, just as the outcomes for many patients with cancer have improved. Bisphosphonate is the standard drug used for bone metastasis of lung cancer, but its safety and effectiveness when used for more than 2 years have not been finally decided. This study reviewed and analyzed the records of 359 patients who received bisphosphonate treatment for up to 24 months or longer than 24 months. It was determined that bisphosphonate used for more than 24 months may increase the risk of calcium deficiency in the bloodstream (hypocalcemia) and kidney disease, but may also delay the development of bone pain, fracture and spinal cord compression or the need for bone radiotherapy or surgery.

A qualitative transcriptional signature for the histological reclassification of lung squamous cell carcinomas and adenocarcinomas.

BACKGROUND: Targeted therapy for non-small cell lung cancer is histology dependent. However, histological classification by routine pathological assessment with hematoxylin-eosin staining and immunostaining for poorly differentiated tumors, particularly those from small biopsies, is still challenging. Additionally, the effectiveness of immunomarkers is limited by technical inconsistencies of immunostaining and lack of standardization for staining interpretation. RESULTS: Using gene expression profiles of pathologically-determined lung adenocarcinomas and squamous cell carcinomas, denoted as pADC and pSCC respectively, we developed a qualitative transcriptional signature, based on the within-sample relative gene expression orderings (REOs) of gene pairs, to distinguish ADC from SCC. The signature consists of two genes, KRT5 and AGR2, which has the stable REO pattern of KRT5 > AGR2 in pSCC and KRT5 < AGR2 in pADC. In the two test datasets with relative unambiguous NSCLC types, the apparent accuracy of the signature were 94.44 and 98.41%, respectively. In the other integrated dataset for frozen tissues, the signature reclassified 4.22% of the 805 pADC patients as SCC and 12% of the 125 pSCC patients as ADC. Similar results were observed in the clinical challenging cases, including FFPE specimens, mixed tumors, small biopsy specimens and poorly differentiated specimens. The survival analyses showed that the pADC patients reclassified as SCC had significantly shorter overall survival than the signature-confirmed pADC patients (log-rank p = 0.0123, HR = 1.89), consisting with the knowledge that SCC patients suffer poor prognoses than ADC patients. The proliferative activity, subtype-specific marker genes and consensus clustering analyses also supported the correctness of our signature. CONCLUSIONS: The non-subjective qualitative REOs signature could effectively distinguish ADC from SCC, which would be an auxiliary test for the pathological assessment of the ambiguous cases.

Soil-Transmitted Helminth Infections in Shanghai, China: Surveillance from 2014 to 2023.

Soil-transmitted helminthiasis remains a notable health problem in developing countries. In 1990 in Shanghai, a city in eastern China, 47% of the population was affected. Due to a series of comprehensive approaches, the prevalence decreased to 0.5% in 2009. We collected 10-year surveillance data to assess the epidemic situation of soil-transmitted helminth (STH) infections in Shanghai. Stool samples and questionnaires from participants were collected. The Kato-Katz technique was used to detect infections with Ascaris lumbricoides, hookworm (Ancylostoma duodenale and Necator americanus), and Trichuris trichiura. From 2014 to 2023, a total of 77,685 participants were screened for parasitic infections, and the overall prevalence of STH infections decreased from 0.1% to 0% in Shanghai. Of 77,685 participants, 25 (0.03%) were positive for intestinal helminths, with the most common parasite being A. lumbricoides (72.0%). Generally, elderly participants from rural areas with lower education levels were more likely to be infected with STHs. A total of 2,914 questionnaires were collected, and most respondents (72.6%) had good knowledge about the transmission routes of STHs. However, 12.3% of participants did not know the damage to health caused by STHs, and 19.3% had no idea of how to prevent infection. These data demonstrate the current state of STH infections in Shanghai. The results suggest that various comprehensive measures should be encouraged, continuously implemented, and strengthened accordingly so that STH elimination can be integrated into the Healthy China initiative by 2030.

Age at menarche and polycystic ovary syndrome: A Mendelian randomization study.

OBJECTIVE: The authors aimed to use a large two-sample Mendelian randomization (MR) study to reveal the causality between age at menarche (AAM) and polycystic ovary syndrome (PCOS) incidence. METHODS: The authors collected summary statistics from the hitherto largest genome-wide association studies conducted in AAM and PCOS in the same ancestry. MR with inverse variance weighting was conducted as the main analysis method, while weighted median and MR-Egger regression were used for comprehensive analysis. As for pleiotropy detection, inverse variance weighting, MR-Egger regression, Mendelian Randomization Pleiotropy Residual Sum and Outlier, as well as leave-one-out analysis were used to detect pleiotropy. Risk factor analysis was conducted to investigate the underlying mechanisms linking AAM to PCOS. RESULTS: Each standard deviation increment in AAM was associated with a significantly lower incidence of PCOS (odds ratio, 0.86 [95% confidence interval, 0.75-0.98]). After adjustment in horizontal pleiotropy by eliminating four outliers, this pathogenic association was still statistically detected. All pleiotropy indexes were without statistical differences, which suggested the conclusions were robust. It showed the causal association between later AAM and lower body mass index, lower fasting insulin level and insulin resistance. CONCLUSION: Our MR analysis verified that a slightly later onset age (15 to 18 years) at menarche could reduce the risk of PCOS. A more comprehensive investigation in a prospective setting is strongly advised.

APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinoma.

Mammalian apurinic/apyrimidinic endonuclease 1 (APE1, APEX1) is a multifunctional enzyme that maintains cellular homeostasis. It is involved in the base excision repair (BER) pathway and plays a key role in radiation-induced DNA damage response. However, the relationship between APE1-driven radiation resistance and pyroptosis in lung adenocarcinoma (LUAD) cells and the underlying molecular mechanisms remain unclear. We found that APE1 was significantly upregulated in LUAD tissues compared to para-carcinoma tissues and promoted the proliferation and invasion of LUAD cells in vitro and in vivo. Mechanistically, APE1 inhibited pyroptosis by inactivating the interferon gene stimulator (STING) pathway via direct interaction with AIM2 and DDX41, as detected by RNA-seq and co-immunoprecipitation. APE1 protects LUAD cells against radiation-induced damage and induces radio-resistance by targeting the STING pathway. It can induce pyroptosis and is negatively regulated by interactions with AIM2 and DDX41. Therefore, APE1 inhibitors should be considered to enhance the radiosensitivity of LUAD cells and improve patient prognosis and therapeutic outcomes. Thus, APE1 play a role in the tumor immune microenvironment and in tumor immunotherapy.

Gut microbiota and risk of five common cancers: A univariable and multivariable Mendelian randomization study.

BACKGROUND: Previous studies have linked gut microbiota with cancer etiology, but the associations for specific gut microbiota are causal or owing to bias remain to be elucidated. METHODS: We performed a two-sample Mendelian randomization (MR) analysis to assess the causal effect of gut microbiota on cancer risk. Five common cancers, including breast, endometrial, lung, ovarian, and prostate cancer as well as their subtypes (sample sizes ranging from 27,209 to 228,951) were included as the outcomes. Genetic information for gut microbiota was obtained from a genome-wide association study (GWAS) comprising 18,340 participants. In univariable MR (UVMR) analysis, the inverse variance weighted (IVW) method was conducted as the primary method, with the robust adjusted profile scores, weighted median, and MR Egger used as supplementary methods for causal inference. Sensitivity analyses including the Cochran Q test, Egger intercept test, and leave-one-out analysis were performed to verify the robustness of the MR results. Multivariable MR (MVMR) was performed to evaluate the direct causal effects of gut microbiota on the risk of cancers. RESULTS: UVMR detected a higher abundance of genus Sellimonas predicted a higher risk of estrogen receptor-positive breast cancer (OR = 1.09, 95% CI 1.05-1.14, p = 2.01 × 10-5 ), and a higher abundance of class Alphaproteobacteria was associated with a lower risk of prostate cancer (OR = 0.84, 95% CI 0.75-0.93, p = 1.11 × 10-3 ). Sensitivity analysis found little evidence of bias in the current study. MVMR further confirmed that genus Sellimonas exerted a direct effect on breast cancer, while the effect of class Alphaproteobacteria on prostate cancer was driven by the common risk factors of prostate cancer. CONCLUSION: Our study implies the involvement of gut microbiota in cancer development, which provides a novel potential target for cancer screening and prevention, and might have an implication for future functional analysis.

Socioeconomic status, individual behaviors and risk for mental disorders: A Mendelian randomization study.

BACKGROUND: There is increasing attention on the association of socioeconomic status and individual behaviors (SES/IB) with mental health. However, the impacts of SES/IB on mental disorders are still unclear. To provide evidence for establishing feasible strategies on disease screening and prevention, we implemented Mendelian randomization (MR) design to appraise causality between SES/IB and mental disorders. METHODS: We conducted a two-sample MR study to assess the causal effects of SES and IB (dietary habits, habitual physical activity, smoking behaviors, drinking behaviors, sleeping behaviors, leisure sedentary behaviors, risky behaviors, and reproductive behaviors) on three mental disorders, including bipolar disorder, major depressive disorder and schizophrenia. A series of filtering steps were taken to select eligible genetic instruments robustly associated with each of the traits. Inverse variance weighted was used for primary analysis, with alternative MR methods including MR-Egger, weighted median, and weighted mode estimate. Complementary methods were further used to detect pleiotropic bias. RESULTS: After Bonferroni correction and rigorous quality control, we identified that SES (educational attainment), smoking behaviors (smoking initiation, number of cigarettes per day), risky behaviors (adventurousness, number of sexual partners, automobile speeding propensity) and reproductive behavior (age at first birth) were causally associated with at least one of the mental disorders. CONCLUSIONS: MR study provides robust evidence that SES/IB play broad impacts on mental disorders.

RNA-binding motif protein 10 represses tumor progression through the Wnt/ß- catenin pathway in lung adenocarcinoma.

RNA-binding motif protein 10 (RBM10), one of the members of the RNA-binding protein (RBP) family, has a tumor suppressor role in multiple cancers. However, the functional role of RBM10 in lung adenocarcinoma (LUAD) and the underlying molecular mechanism remains unclear. In this study, we observed that RBM10 is significantly downregulated in LUAD tissues compared with normal tissues. Low RBM10 expression is significantly associated with poor outcome of LUAD patients. In vitro and in vivo experiments show that RBM10 inhibits cell proliferation, metastasis and EMT progression in LUAD. Mechanistically, we demonstrate that RBM10 interacts with ß-catenin interacting protein 1 (CTNNBIP1) and positively regulates its expression, disrupting the binding of ß-catenin to the transcription factor TCF/LEF, thereby inactivating the Wnt/ß-catenin pathway. In conclusion, this is the first study reporting the role of RBM10 in suppressing LUAD progression at least via partly inactivating the Wnt/ß-catenin pathway, which provides new insights into the tumorigenesis and metastasis of LUAD. Thus, RBM10 may be a promising new therapeutic target or clinical biomarker for LUAD therapy in the future.

Iron Status May Not Affect Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study.

BACKGROUND: Observational studies have shown an association of increased iron status with a higher risk of amyotrophic lateral sclerosis (ALS). Iron status might be a novel target for ALS prevention if a causal relationship exists. We aimed to reveal the causality between iron status and ALS incidence using a large two-sample Mendelian randomization (MR). METHODS: Single nucleotide polymorphisms (SNPs) for iron status were identified from a genome-wide association study (GWAS) on 48,972 individuals. The outcome data came from the largest ALS GWAS to date (20,806 cases; 59,804 controls). We conducted conservative analyses (using SNPs with concordant change of biomarkers of iron status) and liberal analyses (using SNPs associated with at least one of the biomarkers of iron status), with inverse variance weighted (IVW) method as the main analysis. We then performed sensitivity analyses including weighted median, MR-Egger and MR-pleiotropy residual sum and outlier, as well as leave-one-out analysis to detect pleiotropy. RESULTS: In the conservative analyses, we found no evidence of association between four biomarkers of iron status and ALS using IVW method with odds ratio (OR) 1.00 [95% confidence interval (CI): 0.90-1.11] per standard deviation (SD) increase in iron, 0.96 (95% CI: 0.77-1.21) in ferritin, 0.99 (95% CI: 0.92-1.07) in transferrin saturation, and 1.04 (95% CI: 0.93-1.16) in transferrin. Findings from liberal analyses were similar, and sensitivity analyses suggested no pleiotropy detected (all p > 0.05). CONCLUSION: Our findings suggest no causal effect between iron status and risk of ALS. Efforts to change the iron status to decrease ALS incidence might be impractical.

The value of AGR2 and KRT5 as an immunomarker combination in distinguishing lung squamous cell carcinoma from adenocarcinoma.

With the advancement of tumor subtype-specific treatments, precise histopathologic distinction between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) is of significant clinical importance. Nevertheless, the current markers are insufficiently precise in poorly differentiated tissue. This study aimed to establish a histology-specific immunomarker combination to subclassify non-small cell lung cancer (NSCLC) specimens. Based on previous work, we assessed the differential expression of anterior gradient 2 (AGR2) and keratin 5 (KRT5) in ADC and SCC by analyzing public datasets and postoperative specimens. Subsequently, we established a train set (n = 188) and a validation set (n = 42) comprised of NSCLC surgical specimens for training and verifying the subtype-identification capabilities of the two biomarkers separately and in combination, and contrasted the diagnostic utility of AGR2-KRT5 with that of the classic immunomarker combination, TTF1-P40. Differential expression of the two genes was statistically significant in ADC and SCC samples, both at the mRNA and protein levels. The specificity and sensitivity of AGR2 to detect ADC in the training set were 97.0% and 94.4%, while the sensitivity and specificity of KRT5 to determine SCC were 93.9% and 98.9%, respectively. The accuracies of AGR2-KRT5 in ADC, SCC, and across all samples were 93.3%, 92.0% and 92.6% respectively. In the validation cohort, the predictive accuracy of AGR2-KRT5 was up to 100% for ADC and 86.7% for SCC. Compared with TTF1-P40 in ADC samples, AGR2-KRT5 had 8.4% higher accuracy. In summary, the AGR2-KRT5 immunomarker combination reliably distinguished SCC from ADC, and was more accurate than TTF1-P40 in ADC.

Sonodynamic Effects of a Novel Ether-Group Modified Porphyrin Derivative Combined With Pulsed Low-Intensity Ultrasound on PC-9 Cells.

Sonodynamic therapy (SDT) is a developing modality for cancer treatment based on the synergistic effect of ultrasound and chemical compounds which are known as sonosensitizers. The development of more efficient sonosensitizers has become an urgent issue in this field. In this study, a novel porphyrin derivative (BBTPP) mediated SDT was evaluated on PC-9 cells. Pulsed low-intensity ultrasound (PLIU) was used for its little thermal and mechanical damage. The accumulation of drugs in cells was evaluated through porphyrin fluorescence, and the cytotoxicity of BBTPP was evaluated using a cell counting kit-8 assay. The sonodynamic effect was investigated by Hoechst 33342/PI and Annexin V-FITC/PI double staining, which showed an apoptotic rate of 18.87% in the BBTPP-SDT group, as compared with 1.71%, 1.4%, 1.57%, 3.61%, 11.18% in the control, BBTPP, hematoporphyrin monomethyl ether (HMME), ultrasound, and HMME-SDT groups, respectively. The sono-toxic effect of BBTPP was significantly superior to HMME. Our results showed that BBTPP-SDT resulted in much higher intracellular reactive oxygen species (ROS) and lipid peroxidation levels which were evaluated by 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) and Liperfluo assay, respectively. The expressions of Bax, Bcl-2, caspase-9, caspase-8, and cleaved caspase-3 proteins were evaluated to investigate the apoptotic mechanism of BBTPP-SDT. The results of this study showed that the combination of BBTPP and PLIU induced the generation of ROS, resulting in lipid peroxidation, and activated both the extrinsic and intrinsic apoptotic pathways of PC-9 cells. Our results also suggested that the ether group introduced in the side chain of porphyrin could enhance the sono-toxicity of porphyrin-based sensitizers under the sonication of PLIU. These results supported the possibility of BBTPP as a promising sonosensitizer, and an appropriate side chain could enhance the sono-sensitivity of porphyrins.

rs1840680 single nucleotide polymorphism in Pentraxin 3: a potential protective biomarker of severe community-acquired pneumonia.

OBJECTIVE: Single nucleotide polymorphisms (SNPs) of pentraxin 3 (PTX3) are associated with various outcomes of lung infections. This study aimed to analyze the relationship between PTX3 polymorphisms and the severity of community-acquired pneumonia (CAP). METHODS: This is a retrospective case-control study comprising 43 patients with severe CAP (SCAP) and 97 patients with non-severe CAP. Three SNPs in the PTX3 gene (rs2305619, rs3816527, and rs1840680) from peripheral blood samples were genotyped by real-time polymerase chain reaction. The association between each SNP and the CAP severity was analyzed by logistic regression analysis. RESULTS: We found that the rs1840680 polymorphism was significantly associated with CAP clinical severity. However, no such association was observed for the genotypes and allele frequencies of rs2305619 or rs3816527. The PTX3 rs1840680 AG genotype was an independent factor for a lower risk of SCAP after multivariate logistic regression analysis. Male sex and coronary heart disease were associated with an increased risk of SCAP. CONCLUSIONS: The PTX3 rs1840680 AG genotype was found to be associated with a lower risk of SCAP, and may serve as a potential protective biomarker to help clinical judgment and management.

LncRNA NR2F2-AS1 induces epithelial-mesenchymal transition of non-small cell lung cancer by modulating BVR/ATF-2 pathway via regulating miR-545-5p/c-Met axis.

Non-small cell lung cancer (NSCLC) is one type of the most common cancers, which results in the major death worldwide. This study focuses on the understanding of the molecular mechanism of lncRNA NR2F2-AS1 and its regulation on epithelial-mesenchymal transition (EMT) in the development of NSCLC. Expressions of lncRNA NR2F2-AS1, miR-545-5p, c-Met, biliverdin reductase (BVR), ATF-2 and EMT-related markers in NSCLC tissues and cells were measured by western blotting and RT-qPCR assays. The impact of lncRNA NR2F2-AS1 and miR-545-5p on the cell proliferation, migration, invasion and EMT were analyzed by CCK-8, colony formation, wound healing and transwell assays. The interactions among lncRNA NR2F2-AS1, miR-545-5p and c-Met predicted by bioinformatic analysis were evaluated through dual luciferase reporter assay and fluorescence in situ hybridization (FISH). After generating tumor xenografts, immunohistochemistry was utilized to measure the expression of Ki-67 and EMT-related proteins in vivo. Our results showed that lncRNA NR2F2-AS1, c-Met, BVR and ATF-2 were overexpressed while miR-545-5p was silenced in NSCLC tissues and cells. Silencing of lncRNA NR2F2-AS1 or upregulating miR-545-5p significantly inhibited the cell proliferation, migration, invasion and EMT process. The EMT process could be inhibited by suppressing c-Met/BVR/ATF-2 axis. The tumor xenograft experiments demonstrated that the tumor growth and EMT process were significantly inhibited by silencing lncRNA NR2F2-AS1 or overexpression of miR-545-5p in vivo. LncRNA NR2F2-AS1 promoted the NSCLC development through suppressing miR-545-5p to activate EMT process through c-Met/BVR/ATF-2 axis. Our study indicated that lncRNA NR2F2-AS1 and miR-545-5p could be used as potential therapeutic targets to improve NSCLC treatment.

Pentraxin-3 polymorphisms and pulmonary fungal disease in non-neutropenic patients.

BACKGROUND: Pentraxin 3 (PTX3) plays a non-redundant role in innate immunity against fungal diseases. Although single nucleotide polymorphisms (SNPs) of PTX3 are associated with a higher risk of invasive aspergillosis among the immunosuppressed population and chronic obstructive pulmonary disease patients, it is unknown whether PTX3 genetic variants influence the risk of pulmonary fungal disease in immunocompetent patients. METHODS: To investigate the association between PTX3 gene polymorphisms and pulmonary mycosis in non-neutropenic patients, we conducted a case-control study in a tertiary hospital department. Forty-five patients were identified using the criteria of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC-MSG) and enrolled in the case group. Of these patients, 15 had allergic bronchopulmonary aspergillosis (ABPA), 10 had invasive pulmonary aspergillosis (IPA), 18 had pulmonary cryptococcosis, and 2 had other types of pulmonary mycosis. One hundred and twenty-two non-neutropenic inpatients not infected by fungal disease were randomly selected as the control group. We detected three SNPs (rs2305619, rs3816527, and rs1840680) within the PTX3 gene using polymerase chain reaction sequencing and compared their associations with different types of pulmonary fungal disease. RESULTS: Three SNPs were consistent with Hardy-Weinberg equilibrium (HWE). SNP rs2305619 was in linkage disequilibrium with rs3816527 (D'=0.85) and rs1840680 (D'=0.85), respectively. There was no difference in the genotypic distribution and haplotype frequency of the SNPs between the case group and the control group. When we focused on invasive mold infections as a subgroup, we found that the SNP rs3816527 CC homozygote was associated with a higher risk of IPA (OR, 7.37; 95% CI, 0.93-44.44; P=0.033), while the rs3816527 AA homozygote might lower the risk of pulmonary cryptococcosis (OR, 0.35; 95% CI, 0.11-0.96; P=0.047). No genotypic distribution differences were observed for the other two SNPs (rs2305619 and rs1840680). When it came to the comparison between ABPA subgroup and control group, no difference in single nucleotide polymorphism was observed. CONCLUSIONS: This study showed that the SNP rs3816527 is associated with IPA in non-neutropenic patients. Further investigations in large populations are needed to validate this genetic predisposition. Functional studies are also required.

Focused characteristics and effects of light reflected from spherical lipid membrane of giant unilamellar vesicles.

Lipid vesicle is spherical membranous structure with a concave surface on the inside. When a beam of light illuminates a lipid vesicle, the light reflected from the vesicular concave membrane can be focused to have higher intensity and generate enhanced effects. By observing and simulating light reflected from giant unilamellar vesicles (GUVs), the intensity distribution of the light reflected from a spherical concave lipid membrane was investigated. The reflected light had focused characteristics. Its intensity was concentrated 10,000 times and even exceeded the intensity of incident light in a confined region, creating another effective light source in the lipid vesicle. The fluorescence quenching of sulfo-Cy5 encapsulated in spherical GUVs was stronger than that of the outside solution when irradiated by a 632.8 nm laser. When irradiated with ultraviolet light C (UVC), the damage to plasmid DNA encapsulated with spherical GUVs was greater than that of pure plasmid DNA solution and plasmid DNA mixed with lipid membrane fragments. Therefore, in addition to the effects of incident light, the focused light reflected from GUVs could generate incremental effects on encapsulated photoreactive materials if the spherical structure of the lipid membrane was maintained. These results proved that concave lipid membranes of spherical vesicles can focus light and utilize it to generate enhanced effects. The capability of light focusing and its influence on DNA may provide new insights for understanding the function of lipid membranes in cellular life.