Bioinspired Single-Atom Sites Enable Efficient Oxygen Activation for Switching Anodic/Cathodic Electrochemiluminescence.

Exploring advanced co-reaction accelerators with superior oxygen reduction activity that generate rich reactive oxygen species (ROS) has attracted great attention in boosting luminol-O2 electrochemiluminescence (ECL). However, tuning accelerators for efficient and selective catalytic O2 activation to switch anodic/cathodic ECL is very challenging. Herein, we report that enzyme-inspired Fe-based single-atom catalysts with axial N/C coordination structures (FeN5 , FeN4 © SACs) can generate specific ROS for cathodic/anodic ECL conversion. Mechanistic studies reveal that FeN5 sites prefer to produce highly active hydroxyl radicals and afford direct cathodic luminescence by promoting the cleavage of O-O bonds through N-induced electron redistribution. In contrast, FeN4 © sites tend to produce superoxide radicals, resulting in inefficient anodic ECL. Benefiting from the enhanced cathodic ECL, FeN5 SAC-based immunosensor was constructed for the sensitive detection of cancer biomarkers.

Peroxymonosulfate Activation on Synergistically Enhanced Single-Atom Co/Co@C for Boosted Chemiluminescence of Tris(bipyridine) Ruthenium(II) Derivative.

Tris(bipyridine) ruthenium(II)-based luminophores have been well developed in the area of electrochemiluminescence, while their applications in chemiluminescence (CL) are rarely studied due to the poor luminous efficiency and complicated CL reaction. Herein, a novel tris(bipyridine) ruthenium(II)-based ternary CL system is proposed by introducing cobalt single atoms integrated with graphene-encapsulated cobalt nanoparticles (Co SAs/Co@C) and peroxymonosulfate (PMS) as advanced coreaction accelerator and promising coreactant, respectively. On the basis of the experimental results and density functional theory calculations, it is concluded that Co@C can synergistically modulate the adsorption behavior of PMS on Co SAs and then efficiently activate PMS to produce massive singlet oxygen for remarkable CL emission. Under the optimum conditions, the as-prepared CL biosensor exhibits a good linear range, excellent sensitivity, and selectivity, holding great potential for the practical detection of prostate-specific antigen in human serum.

Single-Atom Iron Enables Strong Low-Triggering-Potential Luminol Cathodic Electrochemiluminescence.

The conventional cathodic electrochemiluminescence (ECL) always requires a more negative potential to trigger strong emission, which inevitably damages the bioactivity of targets and decreases the sensitivity and specificity. In this work, iron single-atom catalysts (Fe-N-C SACs) were employed as an efficient co-reaction accelerator for the first time to achieve the impressively cathodic emission of a luminol-H2O2 ECL system at an ultralow potential. Benefiting from the distinct electronic structure, Fe-N-C SACs exhibit remarkable properties for the activation of H2O2 to produce massive reactive oxygen species (ROS) under a negative scanning potential from 0 to -0.2 V. The ROS can oxidize the luminol anions into luminol anion radicals, avoiding the tedious electrochemical oxidation process of luminol. Then, the in situ-formed luminol anion radicals will directly react with ROS for the strong ECL emission. As a proof of concept, sensitive detection of the carcinoembryonic antigen was realized by glucose oxidase-mediated ECL immunoassay, shedding light on the superiority of SACs to construct efficient cathodic ECL systems with low triggering potential.

Marcksb plays a key role in the secretory pathway of zebrafish Bmp2b.

During vertebrate early embryogenesis, the ventral development is directed by the ventral-to-dorsal activity gradient of the bone morphogenetic protein (BMP) signaling. As secreted ligands, the extracellular traffic of BMP has been extensively studied. However, it remains poorly understood that how BMP ligands are secreted from BMP-producing cells. In this work, we show the dominant role of Marcksb controlling the secretory process of Bmp2b via interaction with Hsp70 in vivo. We firstly carefully characterized the role of Marcksb in promoting BMP signaling during dorsoventral axis formation through knockdown approach. We then showed that Marcksb cell autonomously regulates the trafficking of Bmp2b from producing cell to the extracellular space and both the total and the extracellular Bmp2b was decreased in Marcksb-deficient embryos. However, neither the zygotic mutant of marcksb (Zmarcksb) nor the maternal zygotic mutant of marcksb (MZmarcksb) showed any defects of dorsalization. In contrast, the MZmarcksb embryos even showed increased BMP signaling activity as measured by expression of BMP targets, phosphorylated Smad1/5/9 levels and imaging of Bmp2b, suggesting that a phenomenon of "genetic over-compensation" arose. Finally, we revealed that the over-compensation effects of BMP signaling in MZmarcksb was achieved through a sequential up-regulation of MARCKS-family members Marcksa, Marcksl1a and Marcksl1b, and MARCKS-interacting protein Hsp70.3. We concluded that the Marcksb modulates BMP signaling through regulating the secretory pathway of Bmp2b.

Single-Atom-Based Heterojunction Coupling with Ion-Exchange Reaction for Sensitive Photoelectrochemical Immunoassay.

Benefiting from the maximum atom-utilization efficiency and distinct structural features, single-atom catalysts open a new avenue for the design of more functional catalysts, whereas their bioapplications are still in their infancy. Due to the advantages, platinum single atoms supported by cadmium sulfide nanorods (Pt SAs-CdS) are synthesized to build an ultrasensitive photoelectrochemical (PEC) biosensing platform. With the decoration of Pt SAs, the PEC signal of CdS is significantly boosted. Furthermore, theory calculations indicate the positively charged Pt SAs could change the charge distribution and increase the excited carrier density of CdS. Meanwhile, it also suggests that Cu2+ can severely hinder the photoexcitation and electron-hole separation of CdS. As a proof of concept, prostate-specific antigen is chosen as the target analyte to demonstrate the superiority of the Pt SAs-CdS-based PEC sensing system. As a result, the PEC biosensor based on Pt SAs-CdS exhibits outstanding detection sensitivity and promising applicability.

Modulating Oxygen Reduction Behaviors on Nickel Single-Atom Catalysts to Probe the Electrochemiluminescence Mechanism at the Atomic Level.

Luminol-dissolved O2 electrochemiluminescence (ECL)-sensing platforms have been widely developed for sensitive and reliable detection, while their actual ECL mechanisms are still in controversy due to the involved multiple reactive oxygen species (ROS). Different from the structural complexity of nanomaterials, well-defined single-atom catalysts (SACs) as coreaction accelerators will provide great prospects for investigating the ECL mechanism at the atomic level. Herein, two carbon-supported nickel SACs with the active centers of Ni-N4 (Ni-N4/C) and Ni-N2O2 (Ni-N2O2/C) were synthesized as efficient coreaction accelerators to enhance the ECL signals of a luminol-dissolved O2 system. By modulating the surrounding environment of the center metal atoms, their corresponding oxygen reduction behaviors can be well controlled to selectively produce intermediate ROS, giving a great chance to study the following ECL process. According to the experimental and calculated results, the superoxide radical (O2•-) acts as the main radical for the ECL reaction and the Ni-N4/C catalyst with the four-electron pathway to activate dissolved O2 is preferential to enhance ECL emission.

Fe3C-Assisted Single Atomic Fe Sites for Sensitive Electrochemical Biosensing.

The rational construction of advanced sensing platforms to sensitively detect H2O2 produced by living cells is one of the challenges in both physiological and pathological fields. Owing to the extraordinary catalytic performances and similar metal coordination to natural metalloenzymes, single atomic site catalysts (SASCs) with intrinsic peroxidase (POD)-like activity have shown great promise for H2O2 detection. However, there still exists an obvious gap between them and natural enzymes because of the great challenge in rationally modulating the electronic and geometrical structures of central atoms. Note that the deliberate modulation of the metal-support interaction may give rise to the promising catalytic activity. In this work, an extremely sensitive electrochemical H2O2 biosensor based on single atomic Fe sites coupled with carbon-encapsulated Fe3C crystals (Fe3C@C/Fe-N-C) is proposed. Compared with the conventional Fe SASCs (Fe-N-C), Fe3C@C/Fe-N-C exhibits superior POD-like activity and electrochemical H2O2 sensing performance with a high sensitivity of 1225 µA/mM·cm2, fast response within 2 s, and a low detection limit of 0.26 µM. Significantly, sensitive monitoring of H2O2 released from living cells is also achieved. Moreover, the density functional theory calculations reveal that the incorporated Fe3C nanocrystals donate electrons to single atomic Fe sites, endowing them with improved activation ability of H2O2 and further enhancing the overall activity. This work provides a new design of synergistically enhanced single atomic sites for electrochemical sensing applications.

The PIN gene family in cotton (Gossypium hirsutum): genome-wide identification and gene expression analyses during root development and abiotic stress responses.

BACKGROUND: Cell elongation and expansion are significant contributors to plant growth and morphogenesis, and are often regulated by environmental cues and endogenous hormones. Auxin is one of the most important phytohormones involved in the regulation of plant growth and development and plays key roles in plant cell expansion and elongation. Cotton fiber cells are a model system for studying cell elongation due to their large size. Cotton is also the world's most utilized crop for the production of natural fibers for textile and garment industries, and targeted expression of the IAA biosynthetic gene iaaM increased cotton fiber initiation. Polar auxin transport, mediated by PIN and AUX/LAX proteins, plays a central role in the control of auxin distribution. However, very limited information about PIN-FORMED (PIN) efflux carriers in cotton is known. RESULTS: In this study, 17 PIN-FORMED (PIN) efflux carrier family members were identified in the Gossypium hirsutum (G. hirsutum) genome. We found that PIN1-3 and PIN2 genes originated from the At subgenome were highly expressed in roots. Additionally, evaluation of gene expression patterns indicated that PIN genes are differentially induced by various abiotic stresses. Furthermore, we found that the majority of cotton PIN genes contained auxin (AuxREs) and salicylic acid (SA) responsive elements in their promoter regions were significantly up-regulated by exogenous hormone treatment. CONCLUSIONS: Our results provide a comprehensive analysis of the PIN gene family in G. hirsutum, including phylogenetic relationships, chromosomal locations, and gene expression and gene duplication analyses. This study sheds light on the precise roles of PIN genes in cotton root development and in adaption to stress responses.

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2).

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems. FUNDING: Canadian Partnership Against Cancer (Toronto, Canada), Cancer Focus Northern Ireland (Belfast, UK), Cancer Institute New South Wales (Sydney, Australia), Cancer Research UK (London, UK), Centers for Disease Control and Prevention (Atlanta, GA, USA), Swiss Re (London, UK), Swiss Cancer Research foundation (Bern, Switzerland), Swiss Cancer League (Bern, Switzerland), and University of Kentucky (Lexington, KY, USA).

First-morning urinary melatonin and breast cancer risk in the Guernsey Study.

It has been hypothesized that suppressed nocturnal melatonin production is associated with an increased risk of breast cancer, but results from several small prospective studies of the association have been inconclusive. We examined the association between nocturnal melatonin and breast cancer risk in a case-control study nested within the Guernsey III Study, a British prospective cohort study (1977-2009). Concentrations of 6-sulfatoxymelatonin were measured in prediagnostic first-morning urine samples from 251 breast cancer cases and 727 matched controls. Conditional logistic regression models were used to calculate odds ratios for breast cancer in relation to 6-sulfatoxymelatonin level. No significant association was found between 6-sulfatoxymelatonin level and breast cancer risk, either overall (for highest third vs. lowest, multivariable-adjusted odds ratio = 0.90, 95% confidence interval: 0.61, 1.33) or by menopausal status. However, in a meta-analysis of all published prospective data, including 1,113 cases from 5 studies, higher 6-sulfatoxymelatonin levels were associated with lower breast cancer risk (for highest fourth vs. lowest, odds ratio = 0.81, 95% confidence interval: 0.66, 0.99). In summary, we found no evidence that 6-sulfatoxymelatonin level in a first-morning urine sample was associated with breast cancer risk among British women. However, overall the published data suggest a modest inverse association between melatonin levels and breast cancer risk. Further data are needed to confirm this association.

A conserved brassinosteroid-mediated BES1-CERP-EXPA3 signaling cascade controls plant cell elongation.

Continuous plant growth is achieved by cell division and cell elongation. Brassinosteroids control cell elongation and differentiation throughout plant life. However, signaling cascades underlying BR-mediated cell elongation are unknown. In this study, we introduce cotton fiber, one of the most representative single-celled tissues, to decipher cell-specific BR signaling. We find that gain of function of GhBES1, a key transcriptional activator in BR signaling, enhances fiber elongation. The chromatin immunoprecipitation sequencing analysis identifies a cell-elongation-related protein, GhCERP, whose transcription is directly activated by GhBES1. GhCERP, a downstream target of GhBES1, transmits the GhBES1-mediated BR signaling to its target gene, GhEXPA3-1. Ultimately, GhEXPA3-1 promotes fiber cell elongation. In addition, inter-species functional analysis of the BR-mediated BES1-CERP-EXPA3 signaling cascade also promotes Arabidopsis root and hypocotyl growth. We propose that the BES1-CERP-EXPA3 module may be a broad-spectrum pathway that is universally exploited by diverse plant species to regulate BR-promoted cell elongation.

Induced formation of primordial germ cells from zebrafish blastomeres by germplasm factors.

The combination of genome editing and primordial germ cell (PGC) transplantation has enormous significance in the study of developmental biology and genetic breeding, despite its low efficiency due to limited number of donor PGCs. Here, we employ a combination of germplasm factors to convert blastoderm cells into induced PGCs (iPGCs) in zebrafish and obtain functional gametes either through iPGC transplantation or via the single blastomere overexpression of germplasm factors. Zebrafish-derived germplasm factors convert blastula cells of Gobiocypris rarus into iPGCs, and Gobiocypris rarus spermatozoa can be produced by iPGC-transplanted zebrafish. Moreover, the combination of genome knock-in and iPGC transplantation perfectly resolves the contradiction between high knock-in efficiency and early lethality during embryonic stages and greatly improves the efficiency of genome knock-in. Together, we present an efficient method for generating PGCs in a teleost, a technique that will have a strong impact in basic research and aquaculture.

Surrogate production of genome-edited sperm from a different subfamily by spermatogonial stem cell transplantation.

The surrogate reproduction technique, such as inter-specific spermatogonial stem cells (SSCs) transplantation (SSCT), provides a powerful tool for production of gametes derived from endangered species or those with desirable traits. However, generation of genome-edited gametes from a different species or production of gametes from a phylogenetically distant species such as from a different subfamily, by SSCT, has not succeeded. Here, using two small cyprinid fishes from different subfamilies, Chinese rare minnow (gobiocypris rarus, for brief: Gr) and zebrafish (danio rerio), we successfully obtained Gr-derived genome-edited sperm in zebrafish by an optimized SSCT procedure. The transplanted Gr SSCs supported the host gonadal development and underwent normal spermatogenesis, resulting in a reconstructed fertile testis containing Gr spermatids and zebrafish testicular somatic cells. Interestingly, the surrogate spermatozoa resembled those of host zebrafish but not donor Gr in morphology and swimming behavior. When pou5f3 and chd knockout Gr SSCs were transplanted, Gr-derived genome-edited sperm was successfully produced in zebrafish. This is the first report demonstrating surrogate production of gametes from a different subfamily by SSCT, and surrogate production of genome-edited gametes from another species as well. This method is feasible to be applied to future breeding of commercial fish and livestock.

Cilia regulate meiotic recombination in zebrafish.

Meiosis is essential for evolution and genetic diversity in almost all sexual eukaryotic organisms. The mechanisms of meiotic recombination, such as synapsis, have been extensively investigated. However, it is still unclear whether signals from the cytoplasm or even from outside of the cell can regulate the meiosis process. Cilia are microtubule-based structures that protrude from the cell surface and function as signaling hubs to sense extracellular signals. Here, we reported an unexpected and critical role of cilia during meiotic recombination. During gametogenesis of zebrafish, cilia were specifically present in the prophase stages of both primary spermatocytes and primary oocytes. By developing a germ cell-specific CRISPR/Cas9 system, we demonstrated that germ cell-specific depletion of ciliary genes resulted in compromised double-strand break repair, reduced crossover formation, and increased germ cell apoptosis. Our study reveals a previously undiscovered role for cilia during meiosis and suggests that extracellular signals may regulate meiotic recombination via this particular organelle.

Iron Single-Atom Catalysts Boost Photoelectrochemical Detection by Integrating Interfacial Oxygen Reduction and Enzyme-Mimicking Activity.

The investigations on the generation, separation, and interfacial-redox-reaction processes of the photoinduced carriers are of paramount importance for realizing efficient photoelectrochemical (PEC) detection. However, the sluggish interfacial reactions of the photogenerated carriers, combined with the need for appropriate photoactive layers for sensing, remain challenges for the construction of advanced PEC platforms. Here, as a proof of concept, well-defined Fe single-atom catalysts (Fe SACs) were integrated on the surface of semiconductors, which amplified the PEC signals via boosting oxygen reduction reaction. Besides, Fe SACs were evidenced with efficient peroxidase-like activity, which depresses the PEC signals through the Fe SACs-mediated enzymatic precipitation reaction. Harnessing the oxygen reduction property and peroxidase-like activity of Fe SACs, a robust PEC sensing platform was successfully constructed for the sensitive detection of acetylcholinesterase activity and organophosphorus pesticides, providing guidelines for the employment of SACs for sensitive PEC analysis.

Abundance of Early Embryonic Primordial Germ Cells Promotes Zebrafish Female Differentiation as Revealed by Lifetime Labeling of Germline.

Teleost sex differentiation largely depends on the number of undifferentiated germ cells. Here, we describe the generation and characterization of a novel transgenic zebrafish line, Tg(piwil1:egfp-UTRnanos3)ihb327Tg, which specifically labels the whole lifetime of germ cells, i.e., from primordial germ cells (PGCs) at shield stage to the oogonia and early stage of oocytes in the ovary and to the early stage of spermatogonia, spermatocyte, and spermatid in the testis. By using this transgenic line, we carefully observed the numbers of PGCs from early embryonic stage to juvenile stage and the differentiation process of ovary and testis. The numbers of PGCs became variable at as early as 1 day post-fertilization (dpf). Interestingly, the embryos with a high amount of PGCs mainly developed into females and the ones with a low amount of PGCs mainly developed into males. By using transient overexpression and transgenic induction of PGC-specific bucky ball (buc), we further proved that induction of abundant PGCs at embryonic stage promoted later ovary differentiation and female development. Taken together, we generate an ideal transgenic line Tg(piwil1:egfp-UTRnanos3)ihb327Tg which can visualize zebrafish germline for a lifetime, and we have utilized this line to study germ cell development and gonad differentiation of teleost and to demonstrate that the increase of PGC number at embryonic stage promotes female differentiation.

Night Shift Work and Breast Cancer Incidence: Three Prospective Studies and Meta-analysis of Published Studies.

BACKGROUND: It has been proposed that night shift work could increase breast cancer incidence. A 2007 World Health Organization review concluded, mainly from animal evidence, that shift work involving circadian disruption is probably carcinogenic to humans. We therefore aimed to generate prospective epidemiological evidence on night shift work and breast cancer incidence. METHODS: Overall, 522 246 Million Women Study, 22 559 EPIC-Oxford, and 251 045 UK Biobank participants answered questions on shift work and were followed for incident cancer. Cox regression yielded multivariable-adjusted breast cancer incidence rate ratios (RRs) and 95% confidence intervals (CIs) for night shift work vs no night shift work, and likelihood ratio tests for interaction were used to assess heterogeneity. Our meta-analyses combined these and relative risks from the seven previously published prospective studies (1.4 million women in total), using inverse-variance weighted averages of the study-specific log RRs. RESULTS: In the Million Women Study, EPIC-Oxford, and UK Biobank, respectively, 673, 28, and 67 women who reported night shift work developed breast cancer, and the RRs for any vs no night shift work were 1.00 (95% CI = 0.92 to 1.08), 1.07 (95% CI = 0.71 to 1.62), and 0.78 (95% CI = 0.61 to 1.00). In the Million Women Study, the RR for 20 or more years of night shift work was 1.00 (95% CI = 0.81 to 1.23), with no statistically significant heterogeneity by sleep patterns or breast cancer risk factors. Our meta-analysis of all 10 prospective studies included 4660 breast cancers in women reporting night shift work; compared with other women, the combined relative risks were 0.99 (95% CI = 0.95 to 1.03) for any night shift work, 1.01 (95% CI = 0.93 to 1.10) for 20 or more years of night shift work, and 1.00 (95% CI = 0.87 to 1.14) for 30 or more years. CONCLUSIONS: The totality of the prospective evidence shows that night shift work, including long-term shift work, has little or no effect on breast cancer incidence.

Characteristics of the Million Women Study participants who have and have not worked at night.

OBJECTIVES: The aim of this study was to compare the characteristics of women who had and had not worked at night in terms of their risk factors for common disease, indicators of general health, social activities, employment, and sleep behavior. METHODS: The Million Women Study is a large prospective cohort study of women's health in the United Kingdom with 1.3 million women recruited during 1996-2001 (aged 50-64 years) through 66 National Health Service breast screening centers. We analyzed the data from a random sample of 41 652 participants who, in 2009-2010, reported their history of night work. RESULTS: Of the participants, 1 in 8 women (13%) reported that they had ever worked at night and 1 in 50 (2%) reported working at night for ≥20 years. For 33 sociodemographic, behavioral, reproductive, and hormonal factors examined, 20 showed highly significant differences between "ever" and "never" night workers (P<0.0001); 12 showed significant trends by duration of night work (P<0.01). In particular, compared to women who had never worked at night, women who had worked at night were more likely to (i) be of lower socioeconomic status [the odds ratio (OR) for ever versus never night workers of being in the lowest third of socioeconomic status was 1.15, 99% confidence interval (95% CI) 1.06-1.25]; (ii) have ever used hormone replacement therapy (HRT) for the menopause (OR 1.43, 99% CI 1.33-1.55); (iii) be current smokers (OR 1.37, 99% CI 1.19-1.58); and (iv) be obese (OR 1.26, 99% CI 1.15-1.37). Compared to women who had never worked at night, women who had worked at night for ≥20 years were more likely to be (i) of lower socioeconomic status (OR 1.28, 99% CI 1.04-1.57); (ii) nulliparous (OR 1.47, 99% CI 1.12-1.91); (iii) current smokers (OR 1.63, 99% CI 1.18-2.25); and (iv) obese (OR 1.55, 99% CI 1.25-1.93). Former night workers were more likely than never night workers to report a range of sleep disturbances, including poor quality of sleep (OR 1.15, 99% CI 1.01-1.31) and having to take medication to sleep (OR 1.35, 99% CI 1.15-1.60). CONCLUSIONS: Women who reported having worked at night were substantially different from those who reporting never having worked at night and many of the differences would put "ever night workers" at increased risks of cancer, vascular disease, and many other common conditions.