•Each increase of 10 μg/m3 in PM2.5 was associated with decreased fecundity by 11%.•It was also associated with an 20% increased likelihood of infertility.•The association might explain the increased ...infertility rates in polluted areas.
Whether exposure to airborne particulate matter less than 2.5 μm (PM2.5) could impact human fecundity is unclear. We aimed to evaluate the potential impact of PM2.5 exposure on time to pregnancy (TTP) and the prevalence of infertility in the general Chinese population.
We collected reproductive information, sociodemographic characteristics, and lifestyle data of 10,211 couples at risk of pregnancy from a large-scale community-based fertility survey in China. Then, we estimated each participant’s 1-year, 3-year, and 5-year average PM2.5 exposure levels based on remote sensing information. After adjusting for demographic, lifestyle, and environmental co-variables, discrete-time Cox regression models were used to estimate the fecundability odds ratio (FOR) per 10 μg/m3 change of PM2.5. We also estimated the odds ratio (OR) of infertility per 10 μg/m3 change of PM2.5, using logistic regression models.
Among the 10,211 couples, 6,875 (67%) had conceived spontaneously, with a median TTP of 5 months (interquartile range: 2–10 months). The median PM2.5 exposure was 56.8 μg/m3, with a wide range of 9.2–93.5 μg/m3. In Cox regression models, each increase of 10 μg/m3 in the 1-year average PM2.5 exposure was associated with a significant decrease in fecundity by 11% (FOR: 0.89; 95% confidence interval CI: 0.86–0.92). In logistic regression models, it was also associated with an 20% increased likelihood of infertility (OR: 1.20; 95% CI: 1.13–1.27).
PM2.5 exposure was associated with reduced human fecundity, presented by a longer TTP and higher odds of infertility, which might explain the increased infertility rates in areas with heavy PM2.5 pollution.
In order to study the impact of procedures of IVF/ICSI technology on sex ratio in China, we conducted this multi-center retrospective study including 121,247 babies born to 93,895 women in China. ...There were 62,700 male babies and 58,477 female babies, making the sex ratio being 51.8% (Male: Female = 107:100). In univariate logistic regression analysis, sex ratio was imbalance toward females of 50.3% when ICSI was preformed compared to 47.7% when IVF was used (P<0.01). The sex ratio in IVF/ICSI babies was significantly higher toward males in transfers of blastocyst (54.9%) and thawed embryo (52.4%) when compared with transfers of cleavage stage embryo (51.4%) and fresh embryo (51.5%), respectively. Multiple delivery was not associated with sex ratio. However, in multivariable logistic regression analysis after controlling for related factors, only ICSI (adjusted OR = .90, 95%CI: 0.88-0.93; P<0.01) and blastocyst transfer (adjusted OR = 1.14, 95% CI: 1.09-1.20; P<0.01) were associated with sex ratio in IVF/ICSI babies. In conclusion, the live birth sex ratio in IVF/ICSI babies was influenced by the use of ICSI, which may decrease the percentage of male offspring, or the use of blastocyst transfer, which may increase the percentage of male offspring.
Previous studies have shown that GOLPH3 mediates cell growth, proliferation and differentiation and inhibits cell apoptosis; however, the role of GOLPH3 in cumulus granulosa cells and the value of ...GOLPH3 in predicting ICSI pregnancy outcomes remain unknown until now. Our findings showed higher positive expression rate, score of staining intensity, and immunohistochemical score of GOLPH3 in the cumulus granulosa cells of the pregnant women relative to non-pregnant women, and a higher apoptotic rate of cumulus granulosa cells was detected in non-pregnant women than in pregnant women. Pearson correlation analyses revealed that pregnancy correlated negatively with GOLPH3 expression and apoptosis of cumulus granulosa cells, and positively with the number of follicles punctured, number of grade III oocytes, number of eggs retrieved for ICSI, number of zygotes, number of cleavage-stage embryos, number of top-quality embryos, number of blastocysts, number of top-quality blastocysts, and number of frozen embryos. GOLPH3 may be involved in the apoptosis of cumulus granulosa cells, which may correlate with oocyte maturation and egg development. GOLPH3 expression in cumulus granulosa cells may facilitate the selection of top-quality eggs and embryos, the prediction of the clinical pregnancy outcomes of ICSI, and the increase of the pregnancy rate.
The prevalence of infertility in couples actively trying to conceive is 25%. What is the consultation-seeking behaviour, diagnosis and related treatment in infertile couples across China?
Large ...cross-sectional population-based study in 2010–2011, in which 25,270 couples from eight provinces/municipalities in China were approached by a multistage stratified cluster sampling strategy.
Among the 2680 couples reporting infertility, 1246 infertile couples consulted a fertility doctor. Age of the couple, man's body mass index and women's educational level were found to be associated with consultation behaviour. After the fertility work-up, diagnoses were tubal infertility (n = 353, 28.3%), unexplained infertility (n = 311, 25.0%), male infertility (n = 234, 18.8%), ovulatory disorder (n = 194, 15.6%) and endometriosis (n = 34, 2.7%), while 8.6% (n = 107) were not classified. Most couples received non-assisted reproductive technology (ART) fertility treatment (n = 906, 89.3%), with a proportion using traditional Chinese medicine (TCM) (n = 298, 29.4%). Intrauterine insemination (n = 62, 6.1%) and IVF/intracytoplasmic sperm injection (n = 57, 5.6%) were less frequent. Medical treatment and outcomes among five subtypes of infertility were also reported: about 30% of couples with unexplained infertility (n = 94, 30.3%) or male infertility (n = 67, 29.0%) used TCM to treat infertility. Apart from patients with endometriosis, of whom 20.6% (n = 7) received ART, patients with other infertility subtypes rarely received ART. For subsequent fertility outcome, 94% of them did not achieve a pregnancy.
The prevalence of infertility in China is high, but the uptake of treatment is relatively low.
The maintenance technical publications of civil aircraft are important engineering information for maintaining the continued airworthiness of aircraft, strictly guiding the maintenance of aircraft, ...and seriously affecting the efficiency of aircraft maintenance. The commonality between maintenance technical publications corresponding to different aircraft types brings primitive experience to aircraft operators for the maintenance of newly introduced types, which can accelerate the adaptation of maintenance personnel and reduce the maintenance time of aircraft. To quantify the commonality of maintenance technical publications, we constructed a commonality evaluation system for maintenance technical publications by combining the Analytic Hierarchy Process and Fuzzy Comprehensive Evaluation Method. Then, a commonality benefit evaluation model of maintenance technical publications is established by analyzing the impact of commonality on the learning effect, which can analyze and calculate the monthly maintenance time savings of newly introduced models after the effects of commonality. The commonality benefit analysis for maintenance technical publications in this paper is mainly for aircraft operators, which can provide the reference for their decision to introduce new aircraft types.
Microglia play pivotal roles in post-intracerebral hemorrhage (ICH) neural injury. Iron metabolism, which is dysregulated after ICH, participates in microglial dysfunction. Previous studies have ...shown that iron metabolism-related lipocalin-2 (LCN2) is involved in regulating microglial function following ICH. In this study, we investigated the role of LCN2 in microglial function following ICH.
The BV2 (microglia) cell line, transfected with LCN2 for overexpression/interference, received a blood infusion from C57BL/6 mice in vitro. For the in vivo study of LCN2 function, an LCN2 knockout was conducted in mice. Liproxstatin-1 and RSL3 were used to manipulate ferroptosis and to study the effects of LCN2 on microglia after ICH. A BV2 (microglia) cell line, transfected with ferritin light chain (FTL) for overexpression/interference, was co-cultured with primary cultured neurons for a study on the mechanism of LCN2. Behavioral tests were conducted pre-ICH and on days 3, 7, and 28 post-ICH, and the brains and cultured cells were collected for protein, histological, and morphological studies.
Brain LCN2 expression was upregulated in microglia, astrocytes, and neurons and played hazardous roles after ICH. In microglia, LCN2 promoted ferroptosis, which facilitated neural injury after ICH. LCN2-mediated FTL deficiency was shown to be responsible for microglial ferroptosis-induced neural injury.
Our study suggests that LCN2-enhanced microglial ferroptosis plays a detrimental role by inducing FTL deficiency after ICH. The current study reveals a novel molecular mechanism involved in the pathophysiological progression of ICH.
LCN2 expression was elevated in microglia and induced ferritin light chain deficiency that mediated microglia ferroptosis and was marked by mitochondrial structural damage and lipid peroxidation, which facilitated neuron death after ICH. Display omitted
Hemorrhagic stroke causes devastating results, yet neither conservative nor surgical treatment could bring definite benefit to patients. Potential injury mechanisms that substantially participates in intracerebral hemorrhage (ICH) neural damage are still under investigation.
This study investigated the role of lipocalin-2 (LCN2) in microglial function following ICH and revealed that:•Brain LCN2 expression is upregulated in microglia, astrocytes, and neurons and plays hazardous roles after ICH;•LCN2 promotes microglial ferroptosis, which facilitates neural injury after ICH;•LCN2 inhibits the upregulation of microglial ferritin light chain (FTL), but not ferritin heavy chain (FTH) after ICH.•LCN2-mediated FTL inhibition contributes to microglial ferroptosis-induced neural injury.
As technology continues to leap forward and innovations advance, the systems of civil aircraft are becoming increasingly sophisticated and complex. Accordingly, there is a rising amount of ...information to be processed by pilots in the cockpit, increasing their cognitive burden, which significantly threatens the safety of flight. Thus, designers have formulated cockpit layout principles relating to importance, frequency of use, functional grouping, and operation sequence on the basis of ergonomics, which can effectively reduce the cognitive burden for pilots. The degree to which the cockpit layout of a model conforms to the four design principles can indicate its ergonomic design level. In accordance with the concepts of the above four cockpit layout principles, evaluation methods for determining their respective conformity to the four design principles were proposed in this paper. These methods use the operational sequence of cockpit system controls used in the normal flight mission of the actual aircraft type as the evaluation data source. Subsequently, the total evaluation results for cockpit layout were obtained using the weighted accumulation method. Lastly, the process for evaluating the cockpit layouts of civil aircraft was illustrated using the cockpits of the A320 series and B737NG series as examples. Based on the final evaluation results, the feasibility and effectiveness of the proposed evaluation method was verified.
Multiscale simulations of fluids such as blood represent a major computational challenge of coupling the disparate spatiotemporal scales between molecular and macroscopic transport phenomena ...characterizing such complex fluids. In this paper, a coarse-grained (CG) particle model is developed for simulating blood flow by modifying the Morse potential, traditionally used in Molecular Dynamics for modeling vibrating structures. The modified Morse potential is parameterized with effective mass scales for reproducing blood viscous flow properties, including density, pressure, viscosity, compressibility and characteristic flow dynamics of human blood plasma fluid. The parameterization follows a standard inverse-problem approach in which the optimal micro parameters are systematically searched, by gradually decoupling loosely correlated parameter spaces, to match the macro physical quantities of viscous blood flow. The predictions of this particle based multiscale model compare favorably to classic viscous flow solutions such as Counter-Poiseuille and Couette flows. It demonstrates that such coarse grained particle model can be applied to replicate the dynamics of viscous blood flow, with the advantage of bridging the gap between macroscopic flow scales and the cellular scales characterizing blood flow that continuum based models fail to handle adequately.
Heparan sulfate (HS) is a heterogeneous, cell-surface polysaccharide critical for transducing signals essential for mammalian development. Imaging of signaling proteins has revealed how their ...localization influences their information transfer. In contrast, the contribution of the spatial distribution and nanostructure of information-rich, signaling polysaccharides like HS is not known. Using expansion microscopy (ExM), we found striking changes in HS nanostructure occur as human pluripotent stem (hPS) cells differentiate, and these changes correlate with growth factor signaling. Our imaging studies show that undifferentiated hPS cells are densely coated with HS displayed as hair-like protrusions. This ultrastructure can recruit fibroblast growth factor for signaling. When the hPS cells differentiate into the ectoderm lineage, HS is localized into dispersed puncta. This striking change in HS distribution coincides with a decrease in fibroblast growth factor binding to neural cells. While developmental variations in HS sequence were thought to be the primary driver of alterations in HS-mediated growth factor signaling, our high-resolution images indicate a role for the HS nanostructure. Our study highlights the utility of high-resolution glycan imaging using ExM. In the case of HS, we found that changes in how the polysaccharide is displayed link to profound differences in growth factor binding.
It is well‐known that muscle regeneration declines with aging, and aged muscles undergo degenerative atrophy or sarcopenia. While exercise and acute injury are both known to induce muscle ...regeneration, the molecular signals that help trigger muscle regeneration have remained unclear. Here, mass spectrometry imaging (MSI) is used to show that injured muscles induce a specific subset of prostanoids during regeneration, including PGG1, PGD2, and the prostacyclin PGI2. The spike in prostacyclin promotes skeletal muscle regeneration via myoblasts, and declines with aging. Mechanistically, the prostacyclin spike promotes a spike in PPARγ/PGC1a signaling, which induces a spike in fatty acid oxidation (FAO) to control myogenesis. LC–MS/MS and MSI further confirm that an early FAO spike is associated with normal regeneration, but muscle FAO became dysregulated during aging. Functional experiments demonstrate that the prostacyclin‐PPARγ/PGC1a‐FAO spike is necessary and sufficient to promote both young and aged muscle regeneration, and that prostacyclin can synergize with PPARγ/PGC1a‐FAO signaling to restore aged muscles’ regeneration and physical function. Given that the post‐injury prostacyclin‐PPARγ‐FAO spike can be modulated pharmacologically and via post‐exercise nutrition, this work has implications for how prostacyclin‐PPARγ‐FAO might be fine‐tuned to promote regeneration and treat muscle diseases of aging.
Using mass spectrometry imaging, several prostaglandin lipids and fatty acid oxidation (FAO) intermediates are discovered to be injury‐induced myobolites. Detailed studies in vitro and in vivo reveal that the prostacyclin PGI2‐PPARγ/PGC1a‐FAO axis is a key myobolite pathway that spikes transiently to boost muscle regeneration in young mammals, but declines during aging. These myobolites can be targeted to treat aged muscles.
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