Site-Specific Stability Evaluation of Antibody-Drug Conjugate in Serum Using a Validated Liquid Chromatography-Mass Spectrometry Method.

Antibody-drug conjugate (ADC) consists of engineered antibodies and cytotoxic drugs linked via a chemical linker, and the stability of ADC plays a crucial role in ensuring its safety and efficacy. The stability of ADC is closely related to the conjugation site; however, no method has been developed to assess the stability of different conjugation sites due to the low response of conjugated peptides. In this study, an integrated strategy was developed and validated to assess the stability of different conjugation sites on ADC in serum. Initial identification of the conjugated peptides of the model drug ado-trastuzumab emtansine (T-DM1) was achieved by the proteomic method. Subsequently, a semiquantitative method for conjugated peptides was established in liquid chromatography-hybrid linear ion trap triple quadrupole mass spectrometry (LC-QTRAP-MS/MS) based on the qualitative information. The pretreatment method of the serum sample was optimized to reduce matrix interference. The method was then validated and applied to evaluate the stability of the conjugation sites on T-DM1. The results highlighted differences in stability among the different conjugation sites on T-DM1. This is the first study to assess the stability of different conjugation sites on the ADC in serum, which will be helpful for the design and screening of ADCs in the early stages of development.

The effect of mindfulness and psychological capital on mental health of breast cancer patients: Based on polynomial regression and response surface analysis.

OBJECTIVE: To explore the combined effects of mindfulness and psychological capital on mental health of breast cancer patients and to examine the mediating effect of positive emotions in their relationship. METHODS: A convenient sampling method was used in this study, and 522 breast cancer patients aged 18 to 59 who received chemotherapy in a tertiary cancer hospital were enrolled. Polynomial regression with response surface analysis was mainly employed to explore the relationship between mindfulness, psychological capital, and mental health. A block-variable approach was used to verify the mediating effect of positive emotions. RESULTS: In cases of congruence, mental health was better when mindfulness and psychological capital were both high instead of being both low (the slope of the congruence was 0.540, p < 0.001); In cases of incongruence, poorer mental health was found in breast cancer patients with low psychological capital and high mindfulness compared with those who had high psychological capital and low mindfulness (the slope of the incongruence was -0.338, p < 0.001), and the combined effects were a positive curve (positive U-shaped) related to mental health (ß = 0.102, p = 0.040). In addition, positive emotions played a mediating role in the relationship between the block variable (mindfulness and psychological capital) and mental health, and the indirect effect was 0.131. CONCLUSIONS: This study expanded the research on the effects of mindfulness and psychological capital in improving mental health as well as the conflict between the two variables related to mental health by employing a new analytical technique among breast cancer patients.

Conjugation and Topology Engineering of 2D π-d Conjugated Metal-Organic Frameworks for Robust Potassium Organic Batteries.

The evolution of two-dimensional conjugated metal-organic frameworks (2D c-MOFs) provides a significant prospect for researching the next generation of green and advanced energy storage systems (ESSs). Especially, conjugation and topology engineering serve as an irreplaceable character in adjusting the electrochemical properties of ESSs. Herein, we proposed a novel strategy using conjugation and topology engineering to demonstrate the application of 2D c-MOFs in robust potassium-ion batteries (PIBs) for the first time. By comparing 2D c-MOFs with the rhombus/kagome structure as well as three/four-arm core, the rhombus structure (sql-Cu-TBA-MOF) cathode for PIBs can display the impressive electrochemical performance, including a high specific discharge capacity of 178.4 mAh g-1 (at 0.2 A g-1) and a well long-term cycle stability of more than 9,000 (at 10.0 A g-1). Moreover, full PIBs (FPIBs) are constructed by pairing sql-Cu-TBA-MOF cathode with dipotassium terephthalate (KTP) anode, which delivers a high reversible discharge specific capacity of 146.6 mAh g-1 (at 0.1 A g-1) and great practical application prospect. These findings provide reasonable implications for the design of 2D c-MOFs from the perspective of conjugation and topology engineering for advanced energy storage systems.

Ligand-Oxidation-Based Anodic Synthesis of Oriented Films of Conductive M-Catecholate Metal-Organic Frameworks with Controllable Thickness.

Effective control over the crystallization of metal-organic framework (MOF) films is of great importance not only for the performance study and optimization in related applications but also for the fundamental understanding of the involved reticular chemistry. Featuring many technological advantages, electrochemical synthesis has been extensively reported for many MOF materials but is still challenged by the production of dense oriented films with a large-range tuning of thickness. Here, we report a ligand-oxidation-based anodic strategy capable of synthesizing oriented films of two-dimensional (2D) and three-dimensional (3D) conductive M-catecholate MOFs (2D Cu3(HHTP)2, 2D Zn3(HHTP)2, 2D Co3(HHTP)2, 3D YbHHTP, and 2D Cu2TBA) with tunable thicknesses up to tens of micrometers on commonly used electrodes. This anodic strategy relies on the oxidation of redox-active catechol ligands and follows a stepwise electrochemical-chemical reaction mechanism to achieve effective control over crystallizing M-catecholate MOFs into films oriented in the [001] direction. Benefiting from the electrically conductive nature, Cu3(HHTP)2 films could be thickened at a steady rate (17.4 nm·min-1) from ∼90 nm to 10.7 µm via a growth mechanism differing from those adopted in previous electrochemical synthesis of dense MOF films with limited thickness due to the self-inhibition effect. This anodic synthesis could be further combined with a templating strategy to fabricate not only films with well-defined 2D features in sizes from micrometers to millimeters but also high aspect ratio mesostructures, such as nanorods, of Cu3(HHTP)2.

Direct Construction of 2D Conductive Metal-Organic Frameworks from a Nonplanar Ligand: In Situ Scholl Reaction and Topological Modulation.

Two-dimensional conductive metal-organic frameworks (2D c-MOFs) are an emerging class of promising porous materials with high crystallinity, tunable structures, and diverse functions. However, the limited topologies and difficulties in synthesizing suitable organic linkers remain a great challenge for 2D c-MOFs synthesis and applications. Herein, two layered 2D c-MOF polymorphs with either a rhombus structure (sql-TBA-MOF) or kagome structure (kgm-TBA-MOF) were directly constructed via in situ Scholl reaction and coordination chemistry from a flexible and nonplanar tetraphenylbenzene-based ligand (8OH-TPB) in a one-pot manner. Interestingly, the kgm-TBA-MOF comprising hexagonal and triangular dual pores exhibit higher conductivities of 1.65 × 10-3 S/cm at 298 K and 3.33 × 10-2 S/cm at 353 K than that of sql-TBA-MOF (4.48 × 10-4 and 2.90 × 10-3 S/cm, respectively). Moreover, the morphology and topology can be modulated via the addition of ammonium hydroxide as modulator. The present work provides a new pathway for design, synthesis, and topological regulation of 2D c-MOFs.

Effects of recorded maternal voice on anthropometric parameters and heart rate in premature infants: A pilot randomised controlled trial.

PURPOSE: To explore the benefits of a recorded maternal voice intervention on weight, recumbent length, head circumference, and heart rate of preterm infants in the neonatal intensive care unit. METHODS: A pilot randomised controlled trial was conducted in this study. Preterm infants in the neonatal intensive care unit (N = 109) were recruited and randomly assigned to an intervention or control group. Both groups received routine nursing care, while preterm infants in the intervention group received a recorded maternal voice program of 20 min, twice daily for 21 days. Preterm infants' daily weight, recumbent length, head circumference, and heart rate were collected during the 21-day intervention. Participants' heart rate in the intervention group was also recorded once a day pre-during-after the recorded maternal voice program. RESULTS: Preterm infants in the intervention group showed a significant increase in weight (-75.94, 95% CI -108.04, -43.85, P < 0.001), recumbent length (-0.54, 95% CI -0.76, -0.32, P < 0.001), and head circumference (-0.37, 95%CI -0.56, -0.18, P < 0.001) compared with the control group. Preterm infants in the intervention group also showed significant changes in heart rate pre-during-after the recorded maternal voice program. However, no significant differences were found in the heart rate scores between the two groups. DISCUSSION: The changes in heart rate pre-during-after the intervention may help explain participants' more significant increase in weight, recumbent length, and head circumference. PRACTICE IMPLICATIONS: The recorded maternal voice intervention could be incorporated into clinical practice to promote growth and development in preterm infants in the neonatal intensive care unit. STUDY REGISTRATION: Australian New Zealand Clinical Trials Register, https://www.anzctr.org.au/; (registration number: ACTRN12622000019707).

The Relationship Between eHealth Literacy and Mental Health of Adult Workers: A Cross-Sectional Study.

The current cross-sectional study aimed to investigate eHealth literacy among adult workers in China and explore the relationship between eHealth literacy and mental health in this population. Convenience sampling was used to conduct a survey among adult workers aged 18 to 60 years. Potential participants were chosen from those who completed physical examinations at the Health Management Center of one hospital in China. Participants' eHealth literacy and mental health were assessed using the eHealth Literacy Scale, Patient Health Questionnaire, Generalized Anxiety Disorder Scale, and Perceived Stress Scale. Mean scores for eHealth literacy and perceived stress were 28.39 (SD = 5.78) and 5.49 (SD = 2.61), respectively. Depression and anxiety were found in 8.2% and 10.1% of participants, respectively. Multivariate logistic regression analysis showed that a 1-point increase in eHealth literacy score was associated with a 7% decrease in depressive symptoms (odds ratio [OR] = 0.93, 95% confidence interval [CI] [0.88, 0.99]) and a 6% decrease in anxiety symptoms (OR = 0.94, 95% CI [0.89, 0.99]). Furthermore, multiple linear regression analysis showed that perceived stress decreased 0.08 points (B = -0.08, 95% CI [-0.13, -0.04]) with every 1-point increase in eHealth literacy score. Thus, eHealth literacy has the potential to reduce risk of depression, anxiety, and perceived stress, and to promote the mental health of adult workers. [Journal of Psychosocial Nursing and Mental Health Services, 61(9), 40-46.].

Amphiphilic tocopheryl polyethylene glycol succinate as gas chromatographic stationary phase for high-resolution separations of challenging isomers and analysis of lavender essential oil.

This work presents the investigation of using tocopheryl polyethylene glycol succinate as the stationary phase for gas chromatography separations of isomers with different varieties and gas chromatography-mass spectrometry analysis of a wide range of components in lavender essential oil. Its capillary column exhibited moderate polarity and column efficiency of 4000 plates/m determined by n-dodecane at 120°C. As demonstrated, it showed outstanding separation performance toward challenging isomers such as xylenes, alkanes, phenols, and anilines and a wide range of components in essential oils with distinct advantages over the commercial polyethylene glycol and polysiloxane columns. Moreover, its capillary columns displayed excellent repeatability and reproducibility with the RSD values of the retention times in the range of 0.02-0.07% for run-to-run, 0.14-0.22% for day-to-day, and 2.5-4.3% for column-to-column. Its application to gas chromatography-mass spectrometry analysis of the lavender essential oil proved its good potential for practical gas chromatography analyses. To our knowledge, this work presents the first example of employing tocopheryl polyethylene glycol succinate for chromatographic analyses and demonstrates its promising future in this field.

Circulating lncRNA ANRIL in the Serum of Patients with Ischemic Stroke.

BACKGROUND: The current study aims to investigate the expression of antisense noncoding RNA in the INK4 locus (ANRIL) in serum of patients with ischemic stroke and its correlation with high-sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9). METHODS: Real time PCR analysis was carried out to evaluate the level of ANRIL. The levels of hs-CRP and MMP-9 were evaluated using ELISA. ROC analysis was carried out to evaluate the diagnostic value of ANRIL, hs-CRP and MMP-9. Pearson's correlation analysis was carried out to evaluate the expression of ANRIL in serum of hs-CRP and MMP-9. RESULTS: Our data showed that the expression levels of ANRIL, hs-CRP, and MMP-9 in serum of the patients were significantly higher than those of the control group (p < 0.05). Pearson's correlation analysis showed that there was a positive correlation between the expression of ANRIL and hs-CRP and MMP-9. Meanwhile, serum levels of ANRIL, hs-CRP, and MMP-9 in patients with severe neurological deficits were significantly higher than those in patients with moderate and mild neurological deficits (p < 0.05). Moreover, the expression levels of ANRIL, hs-CRP, and MMP-9 in serum of patients with different degrees of neurological impairment have different correlations. More importantly, ROC analysis demonstrated that the combined use of ANRIL, hs-CRP, and MMP-9 demonstrated higher diagnostic value for stroke patients. CONCLUSIONS: Serum ANRIL may be used as a molecular marker in the diagnosis of ischemic stroke and may play an important role in the pathogenesis and development of ischemic stroke in cooperation with hs-CRP and MMP-9.

Accumulation of intact sulfur mustard in adipose tissue and toxicokinetics by chemical conversion and isotope-dilution liquid chromatography-tandem mass spectrometry.

Sulfur mustard (SM) is a powerful vesicant and one of the most harmful chemical warfare agents. Although having been studied for a long time, it is still difficult to fully elucidate the mechanisms of SM poisoning, and there is no effective antidote or specific treatment for SM injury. The investigations on toxicokinetics and tissue distribution of SM will help to understand its toxicity and provide a theoretical basis for pretreatment and therapy of SM poisoning. But the metabolic trajectory or fate of intact SM in vivo remains unclear, and there are insufficient experimental data to elucidate, due to its high reactivity and difficulty in biomedical sample analysis. In this paper, a sensitive method for the detection and quantification of intact SM in blood or tissues using isotope-dilution LC-MS/MS coupled with chemical conversion was developed. By transforming highly reactive SM into stable derivative product, the real concentration of intact SM in biological samples was obtained accurately. The toxicokinetics and tissue distribution studies of intact SM in rats were successfully profiled by the novel method after intravenous (10 mg/kg) or cutaneous administration (1, 3 and 10 mg/kg). The SM level in blood with peak time at 30-60 min determined in cutaneous exposure experiment was found much higher than previously reported, and the mean residence time in blood extended to 1-1.5 h. A significant accumulation of intact SM was observed in adipose tissues, including the perirenal fat, epididymal fat, subcutaneous fat and brown fat, in which the concentrations of SM were at least 15 times greater than those in non-adipose tissues in cutaneous exposed rats. The recovery of SM in body fat was calculated as 3.3 % of bioavailable SM (the bioavailability after cutaneous exposure was evaluated as 16 %). Thus, the adipose tissue was important for SM distribution and toxicity, which may pioneer a new model for both the prevention and treatment of SM exposure.

Perhydroxylcucurbit[6]uril as a highly selective gas chromatographic stationary phase for analytes of wide-ranging polarity.

This work describes the separation performance of a perhydroxylcucurbit[6]uril stationary phase for capillary gas chromatography. The perhydroxylcucurbit[6]uril stationary phase exhibits higher resolving capabilities for critical analytes with better peak shapes than cucurbit[6]uril and conventional stationary phases. The advantageous separation feature of the perhydroxylcucurbit[6]uril stationary phase may originate from its unique structure and favorably balanced interactions with the analytes. Also, the perhydroxylcucurbit[6]uril column shows good separation repeatability with relative standard deviations in the range of 0.01-0.13% for intraday, 0.37-0.82% for interday, and 1.0-4.7% for column-to-column repeatability.

Proteome analysis of soluble nuclear proteins reveals that HMGB1/2 suppress genotoxic stress in polyglutamine diseases.

Nuclear dysfunction is a key feature of the pathology of polyglutamine (polyQ) diseases. It has been suggested that mutant polyQ proteins impair functions of nuclear factors by interacting with them directly in the nucleus. However, a systematic analysis of quantitative changes in soluble nuclear proteins in neurons expressing mutant polyQ proteins has not been performed. Here, we perform a proteome analysis of soluble nuclear proteins prepared from neurons expressing huntingtin (Htt) or ataxin-1 (AT1) protein, and show that mutant AT1 and Htt similarly reduce the concentration of soluble high mobility group B1/2 (HMGB1/2) proteins. Immunoprecipitation and pulldown assays indicate that HMGBs interact with mutant AT1 and Htt. Immunohistochemistry showed that these proteins were reduced in the nuclear region outside of inclusion bodies in affected neurons. Compensatory expression of HMGBs ameliorated polyQ-induced pathology in primary neurons and in Drosophila polyQ models. Furthermore, HMGBs repressed genotoxic stress signals induced by mutant Htt or transcriptional repression. Thus, HMGBs may be critical regulators of polyQ disease pathology and could be targets for therapy development.

Molecular targets of cisplatin in HeLa cells explored through competitive activity-based protein profiling strategy.

Cisplatin is widely used as anticancer drugs, and DNA is considered as the main target. Considering its high affinity towards cysteines and the important role of cystine containing proteins, we applied a competitive activity-based protein profiling strategy to identify protein cysteines that bind with cisplatin in HeLa cells. Living cells were treated with cisplatin at cytotoxic concentrations, then the protein was extracted. After labeling with desthiobiotin iodoacetamide (DBIA) probe, protein was precipitated, digested and isotopically labeled, subsequently the peptides were combined, and the biotinylated cysteine-containing peptides were enriched and quantified by LC-MS/MS. A total of 3571 peptides which originated from 1871 proteins were identified using the DBIA probe. Among them, 46 proteins were screened as targets, including proteins that have been identified as binding proteins by previous study. A novel cisplatin target, calpain-1 (CAPN1), was identified and validated as binding with cisplatin in vitro.

The Mediating Role of Interoceptive Sensitivity in the Relationship between Physical Activity and Depression Symptoms in College Students.

A substantial body of evidence indicates that neurological, psychological, and behavioral health issues are profoundly linked to interoceptive sensitivity. The present study aimed to identify the effects of interoceptive sensitivity on the relationship between physical activity and symptoms of depression in Chinese college students. This study employed a cross-sectional design using convenience sampling. An online self-reported survey was distributed to college students in China. The participants' interoceptive sensitivity, physical activity levels, and depressive symptoms were measured using the MAIA-2, IPAQ-SF, and PHQ-9, respectively. The mediating effect was tested via regression analysis and a parallel mediation model, with bootstrap confidence intervals for indirect effects. The results showed a significant negative correlation between physical activity and depression. A significant positive correlation was observed between physical activity and seven dimensions of interoceptive sensitivity. Conversely, interoceptive sensitivity exhibited a negative correlation with depression. The bootstrap mediation analysis showed that the "not distracting" and "trusting" dimensions of interoceptive sensitivity had significant indirect effects on the relationship between physical activity and depression, suggesting that physical activity might reduce depressive symptoms via these two interoceptive sensitivity dimensions. The findings suggest that interoceptive sensitivity should be integrated into therapeutic interventions, such as physical activity interventions, in the treatment of mental illnesses, particularly depression. Increasing physical activity levels, with a specific focus on enhancing interoceptive modulation, appears to be a promising approach for addressing depression in college students.

Development and Psychometric Evaluation of the Social Participation Questionnaire: A Methodological and Cross-Sectional Study.

PURPOSE: Social participation is vital for the health maintenance of general populations as well as the functional recovery and social ties of clinical patients. To develop a Social Participation Questionnaire (SPQ) to evaluate participation in social activities in an individual's life and to test the reliability and validity of the SPQ. DESIGN: Cross-sectional study. SETTING: Community and clinic in China. SUBJECTS: A total of 1419 healthy adults and 486 breast cancer patients. MEASURES: The initial items were developed from a theoretical framework, a literature review, and Delphi expert consultation. Item analysis, exploratory (EFA) and confirmatory factor analysis (CFA), criterion validity, construct reliability, and internal consistency reliability were performed to examine the psychometric properties of the SPQ. RESULTS: The final SPQ was comprised of 11 different types of social activities, falling under the 3 dimensions of activities of daily life, sports and entertainment activities, and social service activities. EFA explained 50.674% of the total item variance contributing to the tool. CFA showed that the SPQ fit well. The total SPQ score was significantly associated with social network, quality of life, and cognitive function (r = |.180∼.466|, P < .001). The internal consistency coefficient was acceptable (range of Cronbach's alpha, .695 to .720). CONCLUSIONS: The SPQ has robust properties, wide application, and provides a culturally relevant tool to evaluate the social participation of individuals, thus facilitating rigorous clinical and population-based research.

Individual and additive-effect relationships of menopausal symptoms and subjective cognitive decline among nurses during menopausal transition: a cross-sectional study.

OBJECTIVE: This study aimed to examine the individual and additive-effect relationships between menopausal symptoms and subjective cognitive decline among nurses during menopausal transition. METHODS: Between February and September 2019, a convenience sampling strategy was used, involving 1,335 Chinese nurses undergoing menopausal transition. A general information survey that included the Subjective Cognitive Decline Scale and the Menopause Rating Scale was completed. Based on a cut-off point of the subjective cognitive decline score of 7.5, the overall sample was divided into mild and severe groups. Propensity score matching was performed to balance covariates of mild and severe subjective cognitive decline. The individual and cumulative effects of menopausal symptoms and subjective cognitive decline were analyzed using binary logistic regression and the Cochran-Armitage trend test, respectively. RESULTS: After propensity score matching, none of the parameters showed significant differences between the groups. Logistic regression analysis revealed that four menopausal symptoms were closely associated with severe subjective cognitive decline. The Cochran-Armitage trend test indicated odds ratios linking the presence of these symptoms with increased severe subjective cognitive impairment. In addition, nurses simultaneously experiencing two or more core menopausal symptoms were over six times more likely to have severe subjective cognitive decline than nurses experiencing none or one core menopausal symptom during menopausal transition. CONCLUSIONS: Individual and additive numbers of menopausal symptoms significantly influenced subjective cognitive decline in nurses during their menopausal transition. These findings suggest that interventions aimed at enhancing the cognitive performance of nurses experiencing menopause should consider menopausal symptoms.

A Rhombic 2D Conjugated Metal-Organic Framework as Cathode for High-Performance Sodium-Ion Battery.

2D conjugated metal-organic frameworks (2D c-MOFs) have garnered significant attention as promising electroactive materials for energy storage. However, their further applications are hindered by low capacity, limited cycling life, and underutilization of the active sites. Herein, Cu-TBA (TBA = octahydroxyltetrabenzoanthracene) with large conjugation units (narrow energy gap) and a unique rhombus topology is introduced as the cathode material for sodium-ion batteries (SIBs). Notably, Cu-TBA with a rhombus topology exhibits a high specific surface area (613 m2 g-1) and metallic band structure. Additionally, Cu-TBA outperforms its hexagonal counterpart, Cu-HHTP (HHTP = 2,3,6,7,10,11-hexahydroxyltriphenylene), demonstrating superior reversible capacity (153.6 mAh g-1 at 50 mA g-1) and outstanding cyclability with minimal capacity decay even after 3000 cycles at 1 A g-1. This work elucidates a new strategy to enhance the electrochemical performance of 2D c-MOFs cathode materials by narrowing the energy gap of organic linkers, effectively expanding the utilization of 2D c-MOFs for SIBs.

Identification of bile acids in snake bile by hydrogen/deuterium exchange mass spectrometry and quantitative structure-retention relationship analysis.

Natural bile acids, a class of steroids with a valeric acid side chain at the C-17 position, present significant challenges in separation and analysis due to structural similarities, isomerism, and large polarity differences. Therefore, advanced analytical methods are essential for the accurate identification and quantification of bile acids. This study conducted a comprehensive qualitative analysis of bile acids by integrating liquid chromatography-tandem mass spectrometry (LC-MS/MS), hydrogen-deuterium exchange tandem mass spectrometry (HDX-MS/MS), and quantitative structure-retention relationship (QSRR) methods. Firstly, LC-MS/MS conditions were optimized to enhance chromatographic separation and improve the reliability of characteristic fragment ions. MS/MS fragmentation rules for bile acids were derived from the mass spectral data of bile acid standards and validated through HDX-MS/MS experiments. Secondly, potential bile acids in snake bile were identified based on these validated fragmentation rules, and a QSRR model was established to predict the retention times of the proposed structures. Thirdly, HDX-MS/MS was applied to assist in identifying bile acid isomers. Finally, a total of 150 bile acids, including 11 free bile acids (free BA), 5 glyco-bile acids (GBA) and 134 tauro-bile acids (TBA), were detected in snake bile. Thirteen bile acids were accurately characterized by comparing their retention time and MS/MS spectra with standards. Forty-nine bile acids were reasonably annotated using the QSRR model and HDX-MS/MS. This study is notable for being the first to utilize the QSRR and HDX-MS/MS techniques for the annotation of bile acids in snake bile, providing a robust framework for the structural elucidation of these compounds.

Associations of polymorphisms in the genes of FGFR2, FGF1, and RBFOX2 with breast cancer risk by estrogen/progesterone receptor status.

Genetic polymorphisms of fibroblast growth factor receptor 2 (FGFR2) have been demonstrated to be associated with breast cancer risk, presumably through elevation of FGFR2 expression. Fibroblast growth factor 1 (FGF1) and RNA binding protein fox-1 homolog 2 (RBFOX2), which are functionally related to FGFR2, may also associate with breast cancer risk. We investigated the associations between breast cancer risk and the polymorphisms of FGFR2 rs2981582, FGF1 rs250108, and RBFOX2 rs2051579 among 839 incident breast cancer cases and 863 age-matched controls in the Guangzhou Breast Cancer Study. Stratified odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by estrogen receptor (ER)/progesterone receptor (PR) status using multivariate logistic regression. FGFR2 rs2981582 was confirmed to be significantly associated with the risk of ER-positive but not ER-negative breast cancer. In contrast, FGF1 rs250108 was significantly associated with the risk of ER-negative breast cancer (OR (95% CI) = 1.68 (1.20-2.35) for CT + TT vs. CC genotype) but not ER-positive breast cancer. CA + AA genotypes at RBFOX2 rs2051579 were associated with a reduced risk of ER-negative (0.71 (0.52-0.97)) but not ER-positive breast cancer compared to the CC genotype. Similar results were observed when differentiating breast cancer cases by PR status. Neither of the pairs between the three SNPs had a significant interaction on breast cancer risk. Our findings show a suggestively stronger association between FGFR2 rs2981582 and ER-positive breast cancer risk and suggest a greater association of FGF1 rs250108 and RBFOX2 rs2051579 with ER-negative compared to ER-positive breast cancer.

Determination of 48 fragrance allergens in toys using GC with ion trap MS/MS.

This paper presents a method for the simultaneous determination of 48 fragrance allergens in four types of toys (plastic toys, play clays, plush toys, and paper toys) based on GC with ion trap MS/MS. Compared with single-stage MS, MS/MS is superior in terms of the qualification and quantification of a large range of compounds in complicated matrices. Procedures for extraction and purification were optimized for each toy type. The method proved to be linear over a wide range of concentrations for all analytes with correlation coefficients between 0.9768 and 0.9999. Validation parameters, namely, LODs and LOQs, ranged from 0.005-5.0 and from 0.02-20 mg/kg, respectively. Average recoveries of target compounds (spiked at three concentration levels) were in the range of 79.5-109.1%. Intraday and interday repeatabilities of the proposed method varied from 0.7-10.5% and from 3.1-13.4%, respectively. The proposed method was used to monitor fragrance allergens in commercial toy products. Our findings indicate that this method is an accurate and effective technique for analyzing fragrance allergens in materials composed of complex components.