Associations between exposure to phthalates and liver function among women undergoing assisted reproductive technology.

Phthalates can induce hepatotoxicity in animal studies. We aimed to assess the associations of individual and mixture of urinary phthalate metabolites with serum liver function indicators among 764 women undergoing assisted reproductive technology (ART). In linear models, we observed inverse correlations between urinary mono-benzyl phthalate and serum total protein (TP) as well as globulin (ß=-0.27 and -0.23, respectively, P<0.05). Additionally, negative associations were identified between mono-isobutyl phthalate and mono-butyl phthalate (MBP) and aspartate aminotransferase-to-alanine transaminase ratio (AST/ALT) (P<0.05). MBP and the sum of all phthalate metabolites (∑all.phth.m) were positively associated with bilirubin, with ß ranging from 0.14 to 0.47. Most phthalate metabolites were also positively related to gamma-glutamyl transferase (GGT) (all P<0.05). In Bayesian kernel machine regression models, phthalate mixture was positively associated with bilirubin and GGT, whereas inversely associated with AST/ALT and TP. Our results suggest that phthalate exposure may impair liver function among women undergoing ART.

Response of C:N:P stoichiometry to long-term drainage of peatlands: Evidence from plant, soil, and enzyme.

Drought induced by climate warming and human activities regulates carbon (C) cycling of peatlands by changing plant community composition and soil properties. Estimating the responses of peatlands C cycling to environmental changes requires further study of C: nitrogen (N): phosphorus (P) stoichiometric ratios of soil, plants, and enzyme activities. However, systematic studies on the stoichiometry of above-ground and below-ground ecosystems of peatlands post drainage remain scarce. This study compared stoichimetric ratios of plant and soil and stoichimetric ratios of enzyme activities with different functions in two different parts of a minerotrophic peatland, a natural undisturbed part and a part that had been drained for almost 50 years, in Northern China. For the shrub plants, the average C:N:P ratios of leaf in natural and drained peatland were 448:17:1 and 393:15:1, respectively. This indicated that the growth rate of shrub plants is higher in the drained peatland than in the natural peatland, which makes P element more concentrated in the photosynthetic site. However, from the perspective of the dominant plant, the mean C:N:P ratio of Carex leaf was 650:25:1 in the natural peatland, but was 1028:50:1 for Dasiphora fruticosa in drained peatland. This indicated that the intensification of P-limitation of plant growth after drainage. Soil C:N:P ratios of above water table depth (AWT) were 238:15:1 and 277:12:1, but were 383:17:1 and 404:19:1 for below water table depth (BWT) in the natural and the drained peatland, respectively. Soil C:P ratios were greater than the threshold elemental ratio of C:P (174:1), but the soil C:N ratios were less than the threshold elemental ratio of C:N (23:1), which suggested that P was the most limiting nutrient of soil. The soil microbial activities were co-limited by C&P in Baijianghe peatlands. However, the microbial metabolic P limitation was intensified, but the C limitation was weakened for the above water table depth soil after long-term drainage. There are connection between plant-microbe P limitation in peatlands. The P limitation of microbial metabolism was significant positively correlated with soil C:N but negatively with soil moisture. The increase in the lignocelluloses index suggested considerable decomposition of soil organic matter after peatland drainage. These results of stoichiometric ratios from above- to below ground could provide scientific base for the C cycling of peatland undergone climate change.

Phthalate metabolites in urine and follicular fluid in relation to menstrual cycle characteristics in women seeking fertility assistance.

BACKGROUND: Phthalates have been shown to disrupt the estrous cycle in animal studies. However, epidemiological research investigating their associations with menstrual cycle characteristics is limited. OBJECTIVE: To explore the relationships between phthalate exposure and menstrual cycle characteristics among women seeking fertility assistance. METHODS: We determined the levels of eight phthalate metabolites in both follicular fluid (FF) and urine specimens collected from 441 women in the Tongji Reproductive and Environmental (TREE) cohort, using high-performance liquid chromatography and tandem mass spectrometry. Information about menstrual cycle parameters was obtained through a questionnaire. The impacts of individual and joint exposure to phthalates on menstrual cycle characteristics were assessed using multivariable linear regression, Poisson regression, and quantile g-computation approaches. RESULTS: After adjusting for relevant covariates, we found that per log10-unit increase in mono(2-ethylhexyl) phthalate (MEHP) level in urine specimens was associated with a decrease of 0.20 days (95 % CI: -0.37, -0.03) in bleeding duration. We also observed that mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) and the sum of di(2-ethylhexyl) phthalate (DEHP) metabolites (∑DEHP) concentrations in FF samples were inversely related to cycle length [ß = -1.92 (95 % CI: -3.10, -0.75) and -1.87 (95 % CI: -3.56, -0.19), respectively]. However, we generally observed null associations between phthalate metabolites and irregular cycle, dysmenorrhea, hypomenorrhea, or cycle length variation. Furthermore, we also found that phthalate metabolite mixtures in FF and urine were generally unrelated to menstrual cycle characteristics. CONCLUSION: Our findings suggest that some DEHP metabolites in FF and urine are inversely associated with menstrual cycle length and menstrual bleeding duration in women attending a fertility center.

Monomethyl Phthalate Causes Early Embryo Development Delay, Apoptosis, and Energy Metabolism Disruptions Through Inducing Redox Imbalance.

Phthalates are a class of environmental endocrine disrupting chemicals which can cause reproductive system damages. However, data about reproductive toxicity spectrum of phthalate metabolites among Chinese women undergoing in vitro fertilization (IVF) treatments are scarce yet. Previous studies regarding underlying embryo toxicities focused on oxidative stress and apoptosis, while energy metabolism abnormality might be another key cause for embryo developmental disruptions. Here, we found that among the measured eight phthalate metabolites, monomethyl phthalate (MMP) had the second highest urinary concentration in women receiving IVF. Compare to the lowest exposure level group, MMP in tertile 3 was associated with fewer counts of oocyte retrieved and good-quality embryos, and MMP in tertile 2 was correlated with reduced good-quality embryo rate. The direct embryo toxicities of MMP were studied using mouse 2-cell embryos. Consistent to results found in human populations, exposure to MMP induced mouse early embryo developmental delay. Furthermore, MMP exposure led to excessive reactive oxygen species production in early embryos, and antioxidant can partially rescue the early embryo development slow down. Embryo apoptosis could also be caused by oxidative stress. To be noted, elevated apoptosis level was not found in live "slow" embryos but dead embryos, which suggested that apoptosis was not related to early embryo developmental delay. Additionally, MMP exposure depleted adenosine triphosphate (ATP) synthesis of early embryos, which could be reversed by antioxidant. In conclusion, MMP, as the newly found embryonic toxicant in Chinese women, resulted in early embryo development delay, apoptosis, and energy metabolism disruptions via inducing redox imbalance.

Atractylone in the Atractylodes macrocephala Rhizoma Essential Oil and Its Anti-Inflammatory Activity.

The aim of this study was to conduct a screening of potential therapeutic compounds found in the Atractylodes macrocephala rhizoma essential oil (AO) and explore its mechanism of action in the treatment of ulcerative colitis (UC). An inflammation cell model was employed in conjunction with phospho-antibody array technology to explore potential therapeutic compounds of AO and their anti-inflammatory and antioxidant effects. Furthermore, we assessed their efficacy and mechanisms of action in treating dextran sulfate sodium (DSS)-induced colitis in mice. Via the screening process, we identified atractylone (ATR) as the primary active compound in AO. It has been demonstrated that ATR can both decrease the levels of tumor necrosis factor (TNF)-α and reactive oxygen species (ROS) and increase the expression of adhesion proteins such as claudin, ZO-1, and occludin in vitro. Moreover, ATR has been shown to improve UC symptoms in vivo. Via a non-targeted metabolomics analysis of colon tissue, we identified 57 distinct metabolites that responded to ATR treatment. Subsequent analysis of the metabolic pathways revealed that the action of ATR was primarily focused on the amino acid metabolism pathway. In summary, ATR may alleviate the symptoms of UC by regulating multiple signaling pathways. Additionally, ATR has a comprehensive function in anti-inflammation, antioxidative stress, and intestinal injury reduction.

Associations between phthalate metabolites and cytokines in the follicular fluid of women undergoing in vitro fertilization.

Many studies have showed that phthalates have reproductive and embryonic toxicity, while the potential mechanisms are mostly unknown. Inflammation may play a mediating part in phthalate exposure and adverse reproductive endpoints. A cross-sectional survey was conducted to investigate the associations of phthalate metabolites with inflammatory cytokines in the follicular fluid (FF) of women undergoing in vitro fertilization (IVF). We determined the levels of eight phthalate metabolites and five cytokines in the FF of 76 women, including interleukin (IL)- 6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α). The associations of individual phthalate exposure with cytokines in FF samples were explored by multiple linear regression. We further evaluated the combined effects of multiple phthalate exposures on FF levels of cytokines by using Bayesian kernel machine regression (BKMR) models. We found that there was a positive relationship between mono-ethyl phthalate (MEP) and IL-6 in the FF (percent change:12.4%; 95% CI: 1.3%, 24.9%). In contrast, elevated mono-benzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP) and %MEHP levels were associated with decreased MCP-1. In the BKMR models, phthalate metabolite mixtures were positively associated with TNF-α when the mixtures were lower than 65th percentile compared with their medians. In the stratified analyses, MEHP was inversely associated with MCP-1 among women with BMI ≥ 23 kg/m2 (test for interaction <0.05). Our results suggest that certain phthalate metabolites or their mixtures may alter levels of inflammatory cytokines in the FF, and further research is necessary to elucidate the mechanisms underlying the relationship between phthalates exposure, ovarian dysfunction and adverse pregnancy outcomes.

Computational Modeling to Determine the Effect of Phenotypic Heterogeneity in Tumors on the Collective Tumor-Immune Interactions.

Tumor immunotherapy aims to maintain or enhance the killing capability of CD8+ T cells to clear tumor cells. The tumor-immune interactions affect the function of CD8+ T cells. However, the effect of phenotype heterogeneity of a tumor mass on the collective tumor-immune interactions is insufficiently investigated. We developed the cellular-level computational model based on the principle of cellular Potts model to solve the case mentioned above. We considered how asymmetric division and glucose distribution jointly regulated the transient changes in the proportion of proliferating/quiescent tumor cells in a solid tumor mass. The evolution of a tumor mass in contact with T cells was explored and validated by comparing it with previous studies. Our modeling exhibited that proliferating/quiescent tumor cells, exhibiting distinct anti-apoptotic and suppressive behaviors, redistributed within the domain accompanied by the evolution of a tumor mass. Collectively, a tumor mass prone to a quiescent state weakened the collective suppressive functions of a tumor mass on cytotoxic T cells and triggered a decline of apoptosis of tumor cells. Although quiescent tumor cells did not sufficiently do their inhibitory functions, the possibility of long-term survival was improved due to their interior location within a mass. Overall, the proposed model provides a useful framework to investigate collective-targeted strategies for improving the efficiency of immunotherapy.

Synthesis and activity-detection of photoswitchable ligands with fipronil to insect.

BACKGROUND: Ionotropic γ-aminobutyric acid (GABA) receptor (GABAR) in an insect is the major inhibitory receptor and is one of the most important targets for insecticides. Due to the high spatiotemporal resolution of GABAR, the photopharmacological ligands acting on it in vertebrates but not insect have been developed. RESULTS: In this study, two types of photochromic ligands (PCLs) including DTFIPs (DTFIP1 and DTFIP2) and ABFIPs (p-, m-, and o-ABFIP) were synthesized by incorporating photoswitch azobenzene or dithienylethene into fipronil (FIP), which is the antagonist of insect GABAR. Their photomodulation was measured by mosquito larval behavior, and their potential action mechanism was explored by the two-electrode voltage clamp (TEVC) technique in vitro. DTFIP1 and m-ABFIP exhibited the most significant difference of insecticidal activity by about 90- and 5-fold to mosquito larvae between non-irradiated and irradiated formation, respectively, and allowed for optical control of mosquito swimming activity. TEVC assay results indicated that m-ABFIP and DTFIP1 enable optical control over the homomeric LsRDL-type GABAR, which is achieved by regulating the chloride channel of resistance to dieldrin (RDL)-type GABAR by photoisomerization. CONCLUSION: Our results suggested that PCLs synthesized from fipronil provide an alternative and precise tool for studying insect ionotropic GABARs and GABA-dependent behavior. © 2022 Society of Chemical Industry.

Experience of childhood sexual violence and its associations with depressive symptoms among university students in Guangdong, China.

BACKGROUND: Sexual violence, especially childhood sexual violence, is a serious social issue, yet the prevalence of childhood sexual violence among university students is unknown. We aimed to investigate the prevalence of these experiences and assess their associations with depressive symptoms. METHODS: The study included 29,311 participants, mean (SD) age 20.5 (1.4) years, from a cross-sectional survey of a multi-stage stratified cluster random sample from all universities in Guangdong province of China. Data were obtained through an anonymous electronic questionnaire from December 2 to 15, 2019. Undergraduates' experiences of childhood sexual violence were self-reported. Current depressive symptoms were measured by Center for Epidemiological Studies Depression Scale (CESD-10). Stress measures in recent months were measured by the College Student Stress Scale. RESULTS: The prevalence of childhood sexual violence experience among university students was 4.8 % (95 % confidence interval (CI) = 4.6 %-5.0 %), 7.3 % (95 % CI = 6.9 %-7.7 %) for female students and 1.8 % (95 % CI = 1.6 %-2.0 %) for male students. Sexual violence in childhood was related to students' current depressive symptoms after adjustment for stress and socio, demographic characteristics (adjusted prevalence ratio (PRa) = 1.36, 95 % CI = 1.30-1.42). Significant differences in the association between childhood sexual violence and depressive symptoms were also found by sex. CONCLUSIONS: Experiences of childhood sexual violence among university students are not negligible and associated with their current depressive symptoms. The association between childhood sexual violence and depressive symptoms among female and male students is different. Schools, families, and society as a whole should be encouraged to provide education on healthy sexual behavior preventive interventions related to sexual violence for childhood students.

Associations of personal care products use with reproductive outcomes of IVF/ICSI treatment.

Introduction: Personal care products (PCPs) contain a number of endocrine-disrupting chemicals (EDCs) that could potentially affect the reproductive function in women of childbearing age. However, studies focused on the effects of PCPs use on reproductive outcomes are very limited. The current study aimed to explore the relationships between PCPs use patterns and reproductive outcomes in women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. Methods: A total of 1500 women from the Tongji Reproductive and Environmental (TREE) study between December 2018 and January 2020 were included in this study. Participants provided characteristics of PCPs use within the previous three months. Retrieved oocyte number, mature oocyte number, two distinct pronuclei (2PN) zygote number, fertilization rate, cleavage rate, blastocyst formation rate, implantation, clinical pregnancy, miscarriage, and live birth were followed up as reproductive endpoints. Generalized linear regression model was utilized to assess the associations between various categories of PCPs use and reproductive endpoints of IVF/ICSI. Results: After adjusting for relevant covariates, women who used skin care products ≥14 times per week had a reduction of 22.4% in the maturation rate (95% CI: -39.2%, -1.6%) compared to participants who did not use skin care products. After transferring fresh embryos, women who used cosmetics 1-2 times per week (adjusted OR = 2.2, 95% CI: 1.0, 4.8) or 3-7 times per week (adjusted OR = 2.5, 95% CI: 1.2, 5.2) had a higher possibility of miscarriage than those who did not use cosmetics. There was negative association between the use of gel or soap and the cleavage rate among women aged < 30 years old (P for interaction = 0.01). Among women with BMI ≥ 24 kg/m2, the use of gel or soap was negatively associated with the blastocyst formation rate (P for interaction = 0.04), while cosmetics use was negatively associated with the maturation rate (P for interaction = 0.001). Conclusion: Our findings suggest that the use of PCPs in women of reproductive age have a potential adverse impact on IVF/ICSI outcomes, particularly skin care and cosmetic products.

Associations between urinary phthalate concentrations and antral follicle count among women undergoing in vitro fertilization.

Background: Phthalates are ubiquitously used in a variety of products and have an adverse effect on folliculogenesis. However, previous epidemiological studies on the associations between phthalate exposure and antral follicle count (AFC) produced conflicting results. The present study aimed to evaluate the associations between urinary phthalate metabolite concentrations and AFC among women undergoing in vitro fertilization (IVF). Methods: We collected 525 urine samples and measured 8 phthalate metabolites from IVF patients. Poisson regression models were conducted to evaluate the associations between phthalate metabolite concentrations and AFC. In addition, participants were stratified into a younger group (< 35 years) and an older group (≥ 35 years) to explore the potential effect modification by age. We also performed sensitivity analyses by restricting our analyses to only infertile women diagnosed with tubal factor infertility to test the robustness of the results. Results: Significant positive associations were observed among urinary MBP, MEOHP and ∑PAEs concentrations and AFC after adjusting for age, BMI, year of study and infertility diagnosis. Compared with women in the first tertile, women in the third tertile of MBP and MEOHP had 7.02% (95% CI: 1.18%, 12.9%) and 8.84% (95% CI: 2.83%, 14.9%) higher AFC, respectively, and women in the second and third tertiles of ∑PAEs had 6.19% (95% CI: 0.37%, 12.0%) and 9.09% (95% CI: 3.22%, 15.0%) higher AFC, respectively. In addition, MBP, MEOHP and ∑PAEs also had significant positive associations with AFC in trend tests for dose-response. In the age-stratified analysis, we found a stronger relationship between phthalate metabolite concentrations and AFC among older women and an inverse association among younger women. We observed similar results in the sensitivity analyses. Conclusion: We found positive associations between phthalate exposure and AFC, which support the idea that phthalate exposure may accelerate primordial follicle recruitment and lead to higher AFC in women undergoing IVF. More studies are needed to better understand their relationships.

Rescue in vitro maturation may increase the pregnancy outcomes among women undergoing intracytoplasmic sperm injection.

Introduction: To investigate whether rescue in vitro maturation (R-IVM) improves the reproductive outcomes among women undergoing intracytoplasmic sperm injection (ICSI) after one oocyte retrieved cycle. Methods: Between January 2019 and December 2020, 2602 women who underwent ICSI in the Reproductive Medicine Center of Tongji Hospital, Wuhan, China, were included in our retrospective cohort study. There were 2112 women undergoing only ICSI and 490 women with R-IVM followed by ICSI. The intermediate reproductive outcomes and pregnancy outcomes were assessed, including the number of normally fertilized embryos, number of cleaved embryos, number of good-quality embryos, number of day-3 available embryos, number of embryos cultured past day-3, number of blastocysts, number of available blastocysts, biochemical pregnancy, miscarriage, clinical pregnancy and live birth. The perinatal outcomes were also assessed, including preterm birth and birth weight. The abovementioned outcomes were also calculated for in vivo matured and R-IVM oocytes separately in women undergoing ICSI with R-IVM group. Results: Compared with the women who underwent only ICSI, those who underwent ICSI with R-IVM had higher numbers of MII oocytes, normally fertilized embryos, cleaved embryos, day-3 available embryos, embryos cultured past day-3, and higher oocyte maturation rate, available embryo rate than women undergoing only ICSI. Additionally, we found that women undergoing ICSI with R-IVM had an increased chance of clinical pregnancy (adjusted OR=1.50, 95% CI: 1.17-1.93) and cumulative live birth (adjusted OR=1.35, 95% CI: 1.07-1.71). After propensity score matching (PSM), the cumulative live birth rate was 60.1% for women undergoing ICSI with R-IVM versus 54.9% for women undergoing only ICSI (OR=1.24, 95% CI: 0.94-1.63). The reproductive outcomes were also significantly different when calculated for in vivo matured and R-IVM oocytes separately in women undergoing ICSI with R-IVM group. All live births from R-IVM embryos were healthy and without malformations or complications. Conclusion: R-IVM may improve the reproductive outcomes of women undergoing ICSI. It may also provide a reference for the safety of R-IVM. This study maybe support a routine application of R-IVM among patients who intend to undergo ICSI.

Atractylone Alleviates Ethanol-Induced Gastric Ulcer in Rat with Altered Gut Microbiota and Metabolites.

Background: Gastric ulcer (GU) is the most common multifactor gastrointestinal disorder affecting millions of people worldwide. There is evidence that gut microbiota is closely related to the development of GU. Atractylone (ATR) has been reported to possess potential biological activities, but research on ATR alleviating GU injury is unprecedented. Methods: Helicobacter pylori (H. pylori)-induced GU model in zebrafish and ethanol-induced acute GU model in rat were established to evaluate the anti-inflammatory and ulcer inhibitory effects of ATR. Then, 16S rRNA sequencing and metabolomics analysis were performed to investigate the effect of ATR on the microbiota and metabolites in rat feces and their correlation. Results: Therapeutically, ATR inhibited H. pylori-induced gastric mucosal injury in zebrafish. In the ulceration model of rat, ATR mitigated the gastric lesions damage caused by ethanol, decreased the ulcer area, and reduced the production of inflammatory factors. Additionally, ATR alleviated the gastric oxidative stress injury by increasing the activity of superoxide dismutase (SOD) and decreasing the level of malondialdehyde (MDA). Furthermore, ATR played a positive role in relieving ulcer through reshaping gut microbiota composition including Parabacteroides and Bacteroides and regulating the levels of metabolites including amino acids, short-chain fatty acids (SCFAs), and bile acids. Conclusion: Our work sheded light on the mechanism of ATR treating GU from the perspective of the gut microbiota and explored the correlation between gut microbiota, metabolites, and host phenotype.

TRP channels in inflammatory bowel disease: Potential therapeutic targets.

Given the high rate of nonresponse or resistance to current inflammatory bowel disease (IBD) treatments, novel drug targets and biomarkers that aid in therapeutic prediction are eagerly demanded. Transient receptor potential (TRP) channels are distributed in the gastrointestinal tract (GI) and visceral sensory nervous systems with multiple functions. An upsurge is observed in the amount of research that implicates TRP channels in several physiological and pathological process of IBD, suggesting the therapeutic potential of the TRP channels as drug targets for combating IBD. In this review, we focus on the expression levels and functions of TRP channels in GI and discuss their potential roles in IBD, including neuropeptide modulation, immune response, and the effect of TRP channels on the IBD-related pathological activities, and some experimental methods for TRP, providing theoretical support for future research.

cRGD peptide incorporated with patchouli alcohol loaded silk fibroin nanoparticles for enhanced targeting of inflammatory sites in colitis.

The combination therapy of strengthening inflammation regression and mucosal repair may overcome the "therapeutic ceiling" of ulcerative colitis (UC). However, poor targeting is an outstanding challenge in the preparation of drug delivery systems for UC treatment. Here, we developed anti-inflammatory drug (patchouli alcohol, PA)-loaded nanoparticles (NPs) derived from natural silk fibroin (SF) and subjected to surface functionalization with cyclo RGD peptide (cRGD). Self-assembled SF NPs realized sustained drug release. Meanwhile, cRGD functionalization yielded notably targeted drug delivery to inflamed colon, and thereby enhanced the anti-inflammatory and barrier repair capabilities of NPs. Moreover, cRGD-PASFNs regulated innate immune responses and exerted a potent therapeutic efficacy against acute colitis. Surprisingly, the cRGD-PASFNs also modulated the abnormal level of amino acids which are crucial to the integrity of the intestinal barrier. Additionally, oral delivery of this nanomedicine displayed an excellent safety profile in the mouse model. This study confers confidence for the further development of targeted precision therapy for UC and other inflammatory diseases.

Associations of sleep characteristics with outcomes of IVF/ICSI treatment: a prospective cohort study.

STUDY QUESTION: Are sleep characteristics associated with outcomes of IVF/ICSI treatment? SUMMARY ANSWER: Nocturnal sleep <7 h/night and disturbed sleep are related to impaired oocyte and embryo yield, while longer nocturnal sleep might reduce the chance of a successful pregnancy, and the associations between nocturnal sleep duration and IVF/ICSI outcomes are modified by maternal age and subjective sleep quality. WHAT IS KNOWN ALREADY: Disturbed sleep and circadian rhythm contribute to impaired fecundity in the general population, but the effects of sleep characteristics on IVF/ICSI outcomes are largely unknown. STUDY DESIGN, SIZE, DURATION: This study was conducted among 1276 women undergoing IVF/ICSI treatment between December 2018 and September 2019 based on the Tongji Reproductive and Environmental cohort. Owing to the limited number of multiple cycles, we included only the outcomes of their first IVF/ICSI cycle in the current analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on sleep characteristics were collected via questionnaires on the day of oocyte retrieval. IVF/ICSI outcomes were abstracted from medical records. Quasi-Poisson, quasi-binomial or logistic regression models were used to assess the relations between sleep characteristics and reproductive outcomes after adjusting for relevant confounders. We also performed stratified analyses by subjective sleep quality (good versus poor) and maternal age (≤30 versus >30 years). MAIN RESULTS AND THE ROLE OF CHANCE: Compared with women who slept 7 to <8 h/night, those who slept <7 h/night exhibited decreases in the number of retrieved and mature oocytes of 11.5% (95% CI: -21.3%, -0.48%) and 11.9% (95% CI: -22.4%, -0.03%), respectively. A mid-sleep time (MST) earlier than 2:21 a.m. (<2:21 a.m.) or later than 3:00 a.m. (≥3:00 a.m.) and poor subjective sleep quality were inversely associated with the fertilization rate. Women who had trouble falling asleep more than three times per week had a lower number of mature oocytes (-10.5%, 95% CI: -18.6%, -1.6%), normal fertilized oocytes (-14.8%, 95% CI: -23.7%, -4.8%) and good-quality embryos (-15.1%, 95% CI: -25.4%, -3.5%) than those who had no such trouble. In addition, women who slept 9 to <10 h/night had a lower chance of clinical pregnancy compared to women who slept 7 to <8 h/night (odds ratio = 0.65, 95% CI: 0.44, 0.98). In the stratified analyses, the positive associations of nocturnal sleep duration with the number of good-quality embryos and fertilization rate existed only among the women with poor subjective sleep quality (P for interaction = 0.02 and 0.03, respectively). Additionally, we found that the positive associations of nocturnal sleep duration with implantation or clinical pregnancy only existed among women aged over 30 years (P for interaction = 0.04 and 0.01, respectively). LIMITATIONS, REASONS FOR CAUTION: Sleep characteristics are self-reported, which may lead to misclassification. MST serves as a proxy of chronotype and may be non-differentially misclassified resulting in an underestimate of the association of interest. Measuring sleep characteristics on the day of oocyte retrieval may lead to bias. Chance findings cannot be excluded because of the limited number of women with <7 h or ≥10 h nocturnal sleep and multiple testing. Our results may be biased by other confounders and may not be generalizable to women of other ethnicities. WIDER IMPLICATIONS OF THE FINDINGS: Unhealthy sleep characteristics, including short nocturnal sleep, inappropriate sleep time, poor subjective sleep quality and having trouble falling asleep, may impair oocyte quantity and its potential to mature or be fertilized. Long nocturnal sleep might reduce the chance of clinical pregnancy among infertile females, especially women younger than 30 years old. Prolonged nocturnal sleep duration may be a potential beneficial behavior for improving IVF/ICSI outcomes for women aged over 30 years and women with poor subjective sleep quality, which requires further investigation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (81771654) and the National Key R&D Program of China (No. 2018YFC1004201). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

SpBAG3 assisted WSSV infection in mud crab (Scylla paramamosain) by inhibiting apoptosis.

The function of B-cell lymphoma-2 (Bcl-2) family proteins can be divided into two categories: anti-apoptotic and pro-apoptotic. As an anti-apoptotic protein, Bcl2-associated athanogene 3 (BAG3) plays a key role in regulating apoptosis, development, cell movement, and autophagy, and mediating the adaptability of cells to stimulation. However, SpBAG3 has not been reported in mud crab (Scylla paramamosain), and the regulatory effect of SpBAG3 on apoptosis in mud crab and its function in antiviral immunity is still unknown. In this study, SpBAG3 was found, and characterized, which encoded a total of 175 amino acid (molecular mass 19.3 kDa), including a specific conserved domain of the BAG family. SpBAG3 was significantly down-regulated at 0-48 h post-infection with WSSV in vivo. The antiviral effect of SpBAG3 was investigated using RNA interference. The results indicated that SpBAG3 might be involved in assisting the replication of WSSV in the host. SpBAG3 could change the mitochondrial membrane potential (△ψm), and affect cell apoptosis through mitochondrial apoptotic pathways. Therefore, the results of this study suggested that SpBAG3 could assist WSSV infection by inhibiting the apoptosis of the hemocytes in mud crab.

Azobenzene-Avermectin B1a Derivatives for Optical Modulation of Insect Behaviors.

Naturally occurring avermectins are allosteric modulators of glutamate-gated chloride channels (GluCls) and possess exceptionally potent anthelmintic, acaricidal, and insecticidal activities. Here, we develop photoswitchable azobenzene-avermectin (ABAVM) derivatives, which can be photoactivated upon ultraviolet irradiation. After illumination, the best compound p-AB4″AVM had a 1.88-fold and 2.74-fold insecticidal activity enhancement toward Culex pipiens pallens and Mythimna separata larvae, respectively. p-AB4″AVM allows for optical regulation of dorsal unpaired median neuron membrane potential with a 2.15-fold fluorescence intensity decrease after illumination. p-AB4″AVM and p-AB5AVM enable optical modulation of the behavioral response of Culex pipiens pallens larvae with 1- and 4-fold reduced mobility upon irradiation, respectively. The ABAVMs could be used to reversibly manipulate GluCls with light and may be useful for the mechanistic study of macrocyclic lactone insecticides.

NT-proBNP and Major Adverse Cardiovascular Events in Patients with ST-Segment Elevation Myocardial Infarction Who Received Primary Percutaneous Coronary Intervention: A Prospective Cohort Study.

BACKGROUND: The prognostic significance of the amino-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) in patients with ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) has not been fully elucidated. Major adverse cardiovascular events (MACEs) are clinically viable indicators for the accurate, rapid, and safe evaluation of patients with STEMI. This study was designed to investigate the relationship between NT-proBNP levels and the occurrence of short-term MACEs in patients with STEMI who underwent emergency PCI. METHODS: This prospective cohort study included 405 patients with STEMI aged 20-90 years who underwent emergency PCI at the First People's Hospital of Changde City from April 6, 2017, to May 31, 2019. Stent thrombosis, reinfarction, congestive heart failure, unstable angina, and cardiac death were considered as MACEs in this study. The target-independent and -dependent variables were NT-proBNP at baseline and MACE, respectively. RESULTS: There were 28.25% of MACEs. Age, number of implanted stents, Killip class, infarction-related artery, applied intra-aortic balloon pump (IABP), creatine kinase (CK) peak value, CK-MB peak value, TnI peak value, and ST-segment resolution were independently associated with MACE (P < 0.05). In a multivariate model, after adjusting all potential covariates, Log2 NT-proBNP levels remained significantly associated with MACE, with an inflection point of 11.66. The effect sizes and confidence intervals of the left and right sides of the inflection point were 1.07 and 0.84-1.36 (P=0.5730) and 3.47 and 2.06-5.85 (P < 0.0001), respectively. CONCLUSIONS: In patients with STEMI who underwent PCI, Log2 NT-proBNP was positively correlated with MACE within 1 month when the Log2 NT-proBNP was >11.66 (NT-proBNP >3.236 pg/mL).

Ovarian Toxicity and Epigenetic Mechanisms of Phthalates and Their Metabolites.

Ovary plays an important role in the female reproductive system. The maintenance and regulation of ovarian function are affected by various physical and chemical factors. With the development of industrialization, environmental pollutants have caused great harm to public health. Phthalates, as a class of endocrine-disrupting chemicals (EDCs), are synthesized and used in large quantities as plasticizers due to their chemical properties. They are easily released into environment because of their noncovalent interactions with substances, causing human exposure and possibly impairing ovary. In recent years, more and more attention has been paid to the role of epigenetics in the occurrence and development of diseases. And it is urgent to study the role of methylation, gene imprinting, miRNA, and other epigenetic mechanisms in reproductive toxicology.